2015 PHA - Dyslipidemia PDF

The physician may use the recommendations
confidently in caring for most patients, and is meant to

guide practices that meet the needs of patients in most but
not all circumstances. The ultimate decision must be made
by the Filipino physician and patient together, and should
not be a replacement for clinical judgment.
2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines iii
The following organizations are represented:
Voting panel:
PHA-Council on Preventive Cardiology, Council on Coronary Artery
Disease and Council on Hypertension
Philippine Society of Hypertension
Manila Doctors Hospital
Philippine Lipid & Atherosclerosis Society
Philippine College of Physicians
Food and Nutrition Research Institute –

Department of Science and Technology
Department of Health – Republic of the Philippines
Nutritionists-Dietitians Association of the Philippines
Philippine Medical Association
Las Piñas District Hospital
Philippine Society of Endocrinology, Diabetes and Metabolism
Nonvoting panel:
Philippine Health Insurance Corporation
Past Presidents and the Directors of the PHA and the offices of the
PHA President, the PHA Vice President and the PHA Treasurer
iv 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines
Voting Panelists Nannette R. Rey, MD

Aurelia G. Leus, MD
Paul Ferdinand M. Reganit, MD Orlando R. Bugarin, MD
PHA Council on Preventive Cardiology Directors, Philippine Heart Association
Victor L. Lazaro, MD Jorge A. Sison, MD

Jane Villaseñor-Andaman, MD Secretary, Philippine Heart Association
PHA Council on Coronary Artery Disease
Helen Ong-Garcia, MD
Federick C. Cheng, MD Treasurer, Philippine Heart Association
Bernadette S. Halasan, MD
Raymund Paul C. Baello, MD Raul L. Lapitan, MD
PHA Council on Hypertension Vice President, Philippine Heart Association
Romeo U. Merino, MD Alex T. Junia, MD

Camilo G. Te, Jr, MD President, Philippine Heart Association
Manila Doctors Hospital
Eugenio B. Reyes, MD
Rosa Allyn-Sy, MD Joel M. Abanilla, MD
Philippine Lipid and Atherosclerosis Society Past Presidents, Philippine Heart Association
Frederick Philip B. Gloria, MD Adriel E. Guerrero, MD

Philippine College of Physicians Chairman, Philippine Heart Association
Council on Preventive Cardiology
Elmer M. Angus, MD
Philippine Academy of Family Physicians Technical Research Committee
Cecilia Cristina Santos-Acuin, MD Lourdes Ella Gonzalez-Santos, MD

Charmaine A. Duante, RMT, MSc Chair
Food and Nutrition Research Institute –
Department of Science and Technology Members
Imelda V. Caole-Ang, MD
Carmela N. Granada, MD Jude Erric L. Cinco, MD
Department of Health Cecilia A. Jimeno, MD
Elmer Jasper B. Llanes, MD
Adela Jamorabo-Ruiz, RND, MSN, DPA, PhD Raymond V. Oliva, MD
Ms. Elisa D. Toledo Deborah Ignacia D. Ona, MD
Nutritionists-Dietitians Association of the Noemi S. Pestaño, MD
Philippines
Felix Eduardo R. Punzalan, MD
Ma. Janetth B. Serrano, MD Facilitator to the Technical Research
Philippine Medical Association Committee
Ignacia G. Fajardo, MD Steering committee

Las Piñas General Hospital
Leandro C. Bongosia, MD
Bien J. Matawaran, MD Chair
Philippine Society of Endocrinology, Diabetes
and Metabolism Adriel E. Guerrero, MD
Co-chair
Non Voting Panelists Members

Bien J. Matawaran, MD (PSEMD)
Leisa Jeanne Rave C. Gobenciong, MD Albert Atilano, MD (PLAS)
Philippine Health Insurance Corporation Joel M. Abanilla, MD (PHA)
2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 1
2015 Clinical Practice Guidelines for the Management

of Dyslipidemia in the Philippines
Adriel E. Guerrero, M.D.

Chairman, Philippine Heart Association Council
on Preventive Cardiology
Lourdes Ella Gonzalez-Santos, M.D.

Chair, Technical Research Committee
Imelda V. Caole-Ang, M.D.

Jude Erric L. Cinco, M.D.
Cecilia A. Jimeno, M.D.
Elmer Jasper B. Llanes, M.D.
Raymond V. Oliva, M.D.
Deborah Ignacia D. Ona, M.D.
Noemi S. Pestaño, M.D.
Members, Technical Research Committee
Felix Eduardo R. Punzalan, M.D.

Facilitator to the Technical Research Committee
2 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines
CLINICAL QUESTIONS
CQ1 Among patients diagnosed to have dyslipidemia, regardless

of their present morbid condition or risk profile, should
lifestyle modifications (i.e., smoking cessation, weight
management, regular physical activity and adequate blood
pressure monitoring and control) be advised to reduce
overall CV risk?
CQ2 Among non-diabetics without ASCVD but with multiple risk

factors, should statin therapy be given?
CQ3 Among diabetic individuals without ASCVD, should statins

be recommended?
CQ4 Among diabetic individuals without ASCVD, should fibrates

be recommended as an alternative to statin therapy?
CQ5 Among patients with established ASCVD, should statins be

given?
CQ6 Among individuals with ASCVD, should fibrates be given as

an alternative to statins?
CQ7 Among patients with acute coronary syndrome (ACS),

should statin therapy be given?
CQ8 Among patients with established ASCVD or diabetes,

should lipid profile determination be done?
Among patients without ASCVD but with multiple risk
factors, should lipid profile determination be done?
CQ9 Among patients with ASCVD, should omega-fatty acids be

given as an alternative to statin treatment?
CONTENTS
Background................................................................................. 5
Scope of the guidelines............................................................. 5
Methods....................................................................................... 6
Literature Search.......................................................................... 6
Clinical Questions......................................................................... 6
Clinical Outcomes........................................................................ 7
Data Analysis................................................................................ 8
Formulation of Recommendations............................................... 9
Consensus Building...................................................................... 9
Epidemiology of Dyslipidemia in the Philippines.................. 10

CPG CQs and Recommendations............................................. 13
Clinical Question 1................................................................... 13

Statement 1.1 Diet.................................................................... 14
Summary of Evidence................................................................ 14
Addressing Malnutrition.............................................................. 18
Statement 1.2 Smoking Cessation........................................... 19
Use of Electronic Cigarrettes as Alternative to Cigarrette
Smoking and as a smoking cessation aid............................ 20
Statement 1.3 Exercise............................................................ 20
Exercise Prescription.................................................................. 21

Statement 2............................................................................... 22
Comparison with Other Guidelines............................................. 24

Statement 3............................................................................... 25
Recommendation from Other Guidelines................................... 26

Statement 4............................................................................... 27

Statement 5............................................................................... 27
Statin Treatment Goal................................................................ 30


Statement 6............................................................................... 31

Statement 7............................................................................... 31

Statement 8............................................................................... 33
Lipid Determination in Secondary Prevention............................ 34
Lipid Monitoring in Diabetics in Primary Prevention................... 34
Lipid Monitoring in Patients with Familial
Hypercholesterolemia.......................................................... 35
Lipid Determination in Primary Prevention................................. 35
Monitoring for Adverse Drug Reactions...................................... 37
Statin-induced Myopathy............................................................ 37

Statement 9............................................................................... 40
Non-statin Therapy..................................................................... 41
Use of Fibrates in Non-Diabetic Individuals
with Established ASCVD...................................................... 41
Use of Fibrates on Diabetic Individuals without
Established ASCVD............................................................. 42
Summary of the Evidence.......................................................... 42
Use of Omega-3 Fatty Acid........................................................ 45
Summary of the Evidence.......................................................... 45
Combination Therapies.............................................................. 45
HDL Lowering Therapies............................................................ 47
Future Lipid Lowering Therapies................................................ 47
Limitations of the guidelines................................................... 47
Conclusions.............................................................................. 48
References................................................................................ 48
Appendix 1: Included Studies................................................. 55
Appendix 2: GRADE Pro Tables.............................................. 74

BACKGROUND
The Philippine Heart Association, the Philippine Lipid and
Atherosclerosis Society, and the Philippine Society of Endocrinology,
Diabetes, and Metabolism, collaborated to develop the 2015 Clinical
Practice Guidelines for the Management of Dyslipidemia in the
Philippines (2015 CPG). These guidelines are meant to update the 2005
Clinical Practice Guidelines on the Management of Dyslipidemia in the
Philippines (2005 CPG). A panel of experts in the fields of dyslipidemia,
cardiology, endocrinology and clinical epidemiology were assembled
to comprise the technical research committee (TRC) tasked to review
available clinical evidence on dyslipidemia management. Together
with a panel of experts, the TRC developed specific recommendations
regarding the treatment of dyslipidemia among various risk groups.
The main objective for this document is to develop clinical guidelines in
the management of Filipino patients who are diagnosed with elevated
cholesterol. This may influence standards and national policies for
optimal patient care and cardiovascular health.
The physician may use the recommendations confidently in caring
for most patients, and is meant to guide practices that meet the needs
of patients in most but not all circumstances. The ultimate decision must
be made by the Filipino physician and patient together, and should not
be a replacement for clinical judgment.
SCOPE OF THE GUIDELINES

The scope of this CPG includes current statistics on the prevalence
of dyslipidemia in our setting, recommendations on screening and
monitoring using lipid profile determination, identification of groups at
risk for cardiovascular (CV) events which will be targeted for prevention
and treatment, and recommendations for the treatment of dyslipidemia
for the prevention of CV events and mortality in Filipinos.
Primary prevention refers to interventions in patients without
prior coronary heart disease (CHD) or other clinical atherosclerotic
cardiovascular disease (ASCVD). Primary prevention of CV events
targets individuals who are considered to be at-risk including those
with diabetes mellitus (DM) or multiple risk factors (i.e., advanced age,
male gender, smoking, hypertension, body mass index [BMI]> 25 kg/m2,
family history of premature CHD[first-degree relatives with fatal or non-
fatal myocardial infarction, coronary angioplasty, coronary artery bypass
surgery or stroke before the age of 55 years in male relatives or before
65 years of age in female relatives]1, familial hypercholesterolemia [an
elevated cholesterol level > 190 mg/dL, the presence of xanthomas and
a family history of premature cardiovascular disease]2, and laboratory
findings of microalbuminuria, proteinuria, menopausal status, and left

ventricular hypertrophy.
Secondary prevention refers to interventions in patients with known
ASCVD in order to prevent another CV event, and targets those with
prior CHD, transient ischemic attack, stroke, carotid artery disease, and
clinical peripheral arterial disease (PAD). The TRC has also identified
those with acute coronary syndrome (ACS) as an important at-risk
group for which a separate recommendation has been made, which is a
significant update from the 2005 CPG.
This CPG evaluated major classes of only locally available
medications, focusing on those that are widely used in practice, and/or
those that would provide the most benefit in terms of CV risk reduction.
Furthermore, clinical questions that were most relevant to clinical
practice were identified, as well as the applicability of recommendations
to local clinical scenarios.
METHODS
The TRC initially reviewed the recommendations in the 2005 CPG
and proposed clinical questions to be answered by the 2015 CPG. In
order to update the 2005 CPG, the current guideline generally used
the same methods as the earlier document. The TRC specified the
population, intervention and outcomes for each clinical question, and
defined the criteria for eligible studies.
LITERATURE SEARCH
The TRC searched for all published studies, both local and
international, pertaining to the above 9 clinical questions, with the use
of electronic search engines and manual search. Unpublished data
were also retrieved, whenever possible. To formulate the nutrition
recommendations, the Work Group used randomized controlled trials
(RCTs), meta-analyses, and systematic reviews of studies carried out
in adults (≥18 years of age) with or without established coronary heart
disease/CVD and with or without risk factors for coronary heart disease/
CVD, and diagnosed with elevated blood cholesterol.
CLINICAL QUESTIONS
The TRC developed an initial set of questions based on their
expertise and from the 2005 CPG. From the initial document, nine (9)
clinical questions (CQs) were prioritized and were used to provide the
guidelines for the 2015 CPG (Table 1).
Several of these CQs were updates from the 2005 CPG. Clinical
question (CQ) 1, in particular, is an update based on the combined
Statements 1 to 3 of the 2005 CPG. This question still referred to the

reduction in overall CV risk. Critical appraisal of evidence was divided
according to intervention (i.e., low-fat, low-cholesterol diet; smoking
cessation; and physical activity). Other CQs are also updates from the
previous guideline.
Clinical Questions 8 and 9 are newly added and were deemed
relevant based on the prevailing local practice of statin of high risk
patients with acute coronary syndrome. The use of omega 3 fatty acid
is also relevant as this has been used as secondary prevention among
patients with or without diabetes mellitus.
CLINICAL OUTCOMES
Various clinical outcomes were rated and ranked using the Grades of
Recommendation, Assessment, Development and Evaluation (GRADE)
categories of importance. The clinical outcomes were rated numerically
Table 1. Clinical Questions

Clinical Questions
CQ1 Among patients diagnosed to have dyslipidemia, regardless of
their present morbid condition or risk profile, should lifestyle
modifications (i.e., smoking cessation, weight management,
regular physical activity and adequate blood pressure
monitoring and control) be advised to reduce overall CV risk?
CQ2 Among non-diabetics without ASCVD but with multiple risk
CQ3 Among diabetic individuals without ASCVD, should statins be
recommended?
CQ4 Among diabetic individuals without ASCVD, should fibrates be
recommended as an alternative to statin therapy?
CQ5 Among patients with established ASCVD, should statins be
given?
CQ6 Among individuals with ASCVD, should fibrates be given as an
alternative to statins?
CQ7 Among patients with acute coronary syndrome (ACS), should
statin therapy be given?
CQ8 Among patients with established ASCVD or diabetes, should
lipid profile determination be done?
Among patients without ASCVD but with multiple risk factors,
should lipid profile determination be done?
CQ9 Among patients with ASCVD, should omega-fatty acids be
given as an alternative to statin treatment?
on a 1-to-9 scale following the GRADE categories, where a score of

7-9 is critical; 4 -6 important; and 1- 3, of limited importance. According
to GRADE, ranking outcomes by their relative importance can help to
focus attention on those outcomes that are considered most important
and help to resolve or clarify disagreements.
The TRC designated the following outcomes to be CRITICAL with
a score of 9:
• Total mortality
• Cardiovascular deaths;
• Fatal and non-fatal myocardial infarction and
• Stroke or cerebrovascular disease.
Cardiovascular events was ranked as CRITICAL with a Score of
7. Coronary revascularization was assigned to be an IMPORTANT
outcome with a GRADE PRO Score of 6. Additional important outcomes
were added when deemed necessary for the particular clinical scenario
(e.g., angina in ACS).
Data on these six outcomes were extracted from the retrieved
studies.
DATA ANALYSIS
The extracted data from retrieved studies were pooled and analyzed
using the GRADE-PRO software. The quality of evidence and risks of
biases were also evaluated using GRADE-PRO. Evidence quality and
risk of bias were based on:
• Study design;
• Study limitations – These could include lack of allocation
concealment; lack of blinding particularly for subjective outcomes;
losses to follow-up; failure to adhere to an intention to treat analysis;
stopping early for benefit; failure to report outcomes;
• Study inconsistencies – Widely varying effects or study
heterogeneity;
• Indirectness of evidence – Applicability of the study to the
specific clinical question based on various study characteristics (e.g.,
ethnicity, choice of comparators, etc.);
• Study imprecision – Few included patients or reported events;
and,
• Other identified limiting characteristics.
Standardized summary of evidence tables was used to present the
quality of the evidence and key results in a transparent and reproducible
fashion. These are presented in the subsequent sections.
To aid in quantifying treatment effect, numbers-needed-to-treat
(NNTs) were reported in interventions with significant benefit to specific
Table 2. Criteria for recommendation

Quality of Outcome NNT Recommendation
Evidence
High Critical Low Strongly Recommend
Moderate Critical Low Recommend
Moderate Important Low May Recommend
Low Critical or High or not Do not recommend
important significant
outcomes. By convention, NNTs are adjusted to the local prevalence

of disease and outcomes. According to the 2008 National Nutrition
and Health Survey, the prevalence of CHD in the Philippines was
1.1%.2 This is around a third of the reported prevalence in the United
States. However, the TRC believes that the local prevalence could be
underestimated, since the NNHES definition of CHD was a diagnosis by
a physician or nurse (e.g., from a previous heart attack). Furthermore,
should a Filipino patient experience acute coronary syndrome (ACS)
and was admitted to a tertiary hospital, the mortality rate as reported by
the ACS registry is 7.8%, which is only slightly higher than the mortality
reported in the United States (6.3%).3,4 Hence, the NNTs from Western
studies were not adjusted, under the assumption that local prevalence
rates and mortality rates were not significantly different from Western
countries.
FORMULATION OF RECOMMENDATIONS
Recommendations based on the 9 clinical questions were
formulated, taking into account the following results in each summary of
evidence table (Table 2):5
• Quality of evidence for each outcome;
• Treatment effect for each outcome; and,
• Relative importance of outcomes.
With regard to the recommendation on the use of lipid profile
determination, draft recommendations were formulated so as to
facilitate the implementation of the therapeutic interventions (e.g.,
lifestyle modification, statins, and non-statins) recommended in these
2015 CPG.
CONSENSUS BUILDING
Draft recommendations were written and presented to the
members of the TRC and were subsequently modified. These guideline
recommendations were then subjected to external review by a panel
Table 3. Trends of Lipid Profiles of Filipinos Based on NNHeS Data

Lipid parameter Prevalence, %
2003 2008 2013
Borderline (200-239 mg/dL) to High 33.5% 41.6% 46.9%
( > 240 mg/dL) Total Cholesterol
Bordeline (130-159) to high (≥ 160 43.2% 43.2% 47.2%

mg/dL) LDL-Cholesterol
HDL-C < 40 mg/dL 54.2% 64.1% 71.3%

Elevated Triglyceride ≥ 150 mg/dL 30% 46.5% 38.6%
Reconstructed from the 2003, 2008 and 2013 FNRI NNHES data
* Based on ATP-III cut –off values
of experts representing local stakeholders in the care of dyslipidemia.

During the panel meetings, the process of guideline development and the
method for consensus building was first presented. The clinical questions
were presented to the expert panel for feedback and modification.
Subsequently, the members of the TRC presented the questions, the
answers to the question (recommendations) based on the summary of
the evidence and the GRADE table of appraisal. Comparison of the
recommendations with other guidelines was provided if applicable.
The expert panel then voted on the recommendations. Any proposed
changes to the recommendation were also voted on after thorough
discussion. The results of the panel meetings are presented here as the
final recommendations.
EPIDEMIOLOGY OF DYSLIPIDEMIA IN THE PHILIPPINES

Diseases of the heart and vascular system made up 33.0% of all
deaths in the Philippines according to the World Health Organization-
Non Communicable Diseases (WHO-NCD) Country Profiles 2014.6
Historically, based on our national surveys conducted, the prevalence of
dyslipidemia continues to increase as seen in Table 3.
In the 2008 National Nutrition and Health Survey Group (NNHeS)
report, the prevalence of coronary artery disease (CAD) in the Philippines
was 1.3%.2 The peak prevalence was noted at age group 60-69 where
5% of this age group had coronary disease. The prevalence of CAD in
rural areas was 1.0% and 1.7% in the urban areas. Moreover, based
on the ACS registry as of 2013, diabetes is considered as the second
highest risk factor among patients with acute coronary syndrome.3 The
prevalence of diabetes mellitus increased significantly from 4.8 in 2008
to 5.4 in 2013 (p=0.0336).
The NNHeS is a nationwide survey conducted every 5 years by

the Food and Nutrition Research Institute of the Department of Science
and Technology, in partnership with several government agencies
and non-governmental organizations such as the Philippine Lipid
and Atherosclerosis Society, Philippine Society of Hypertension and
the Philippine Heart Association. As part of the NNHeS, data on the
prevalence of risk factors for non-communicable diseases are gathered.
The latest survey was conducted in 2013 and the results revealed that
the overall prevalence of high total cholesterol (defined as greater than
240 mg/dL) among adults aged 20 years and above was at 46.9%.7
The age group of 40-49 years was the lowest age group to have an
overall prevalence (50.6%) higher than the national average. All other
age groups older than this also had a prevalence ranging from 54.6% to
61.8% (Figure 1).
The overall prevalence of high LDL-C (defined as greater than 160
mg/dL) was at 47.2%, with an age distribution similar to that of total
cholesterol (Figure 2).
Figure 1. Prevalence of high total cholesterol (>240 mg/dL) among

adult Filipinos by age group
Figure 2. Prevalence of high LDL-C (>160 mg/dL) among adult

Filipinos by age group
The overall prevalence of low HDL-C (defined as less than 40 and

50 mg/dL for males and females, respectively) was very high at 71.3%,
with a relatively even age distribution (Figure 3).
Finally, the prevalence of borderline (150-190 mg/dL) to very high
triglycerides (>400 mg/dL) was 38.6%. Again, the age group of 40-49
was where the prevalence of high triglycerides began to exceed the
national average (Figure 4).
The prevalences of other risk factors were as follows:
• 6.8% for obesity (defined as a BMI of 30 or higher) and peaking
at age 40-45 years;
• 22.3% for hypertension (defined as a systolic BP of at least 140
or a diastolic BP of at least 90) accelerating at age 40-49 years;
• 5.4% for diabetes (defined as a fasting blood sugar of at least
126 mg/dL) accelerating at age 40-49 years and peaking at age 60-69
years;
Figure 3. Prevalence of low HDL-C (<40 for males and <50 mg/dL
for females) among adult Filipinos by age group
Figure 4. Prevalence of borderline (150-190 mg/dL) to very high

triglycerides (>400 mg/dL) among adult Filipinos by age group
• 25.4% for smoking, with a relatively even age distribution; and,

• 45.2% for insufficient physical activity, with an inverted
distribution peaking at ages 20-29 years, and 70 years and above.
As a general trend, risk factors tend to surpass the national averages
at the age group of 40-49 years, making individuals in this age group an
important lower threshold for preventive care.
CPG CQs and Recommendations

The abovementioned nine clinical questions were screened,
researched and analyzed by the TRC. Statements were constructed to
answer the clinical questions and were presented to the voting panel.
The panel decided which of the statements would be applicable to the
Filipino dyslipidemia patients. Six of the clinical questions were retained
to answer the clinical questions. However, there were issues on clinical
questions on non-statin therapies (CQs 4,6 and 9) so no statements
were made. The TRC and the voting panel decided to provide a section
on the use of non-statin therapy despite the lack of clinical data. The
section on non-statin treatment would serve as a guide for clinicians in
managing their patients, who are on maximally-tolerated statins and are
not yet on goal. Thus, the 2015 CPG has nine clinical questions but only
six statements.
Clinical Question 1
CQ1. Among patients diagnosed to have dyslipidemia, regardless of
their present morbid condition or risk profile, should lifestyle modification
(i.e., smoking cessation, weight management, regular physical activity
and adequate blood pressure monitoring and control) be advised to
reduce overall CV risk?
The importance of lifestyle modifications, such as proper diet and
exercise, has been repeatedly emphasized and been given increasing
attention because of their relation to cardiovascular disease. The TRC
recommends that patients with dyslipidemia should undertake
lifestyle modification regardless of their risk profile. Specific
recommendations for this clinical question are on diet, exercise and
smoking. Recommendations on adequate blood pressure control and
weight loss are already documented in the guidelines of the Philippine
Society of Hypertension (PSH) and Philippine Association in the Study
of Overweight and Obesity (PASOO), respectively.
Statement 1.1 Diet

For individuals at any level of cardiovascular risk, especially those
with established atherosclerotic cardiovascular disease (ASCVD), a low-
fat, low cholesterol diet, rich in fruits and vegetables, is RECOMMENDED.
Summary of Evidence
The basis for reducing or modifying fat in the diet was an updated
meta-analysis of forty-eight (48) randomized controlled trials8, which
included 60 comparison arms and 71,770 participants. The meta-
analysis included randomized controlled trials that enrolled adults (18
years old or older, no upper age limit), at any risk for cardiovascular risk.
Participants were of any gender, although those who were acutely ill,
pregnant or lactating were excluded in the studies.
The intervention was reduction or modification of dietary fat or
cholesterol, such as would be expected to result in improvement of
serum lipid profile. These interventions included an intention to reduce
total fat intake, modify fat intake, and reduce and modify fat intake,
compared to a usual diet type of control. A low fat diet aimed to reduce
fat intake to less than 30% energy from fat, and at least partially replace
the energy lost with carbohydrates (simple or complex), protein or fruit
and vegetables. A modified fat diet aimed to include 30% or more energy
from total fats, and included higher levels of mono-unsaturated or poly-
unsaturated fats than the “usual diet”. Low cholesterol was pegged at
150 mg/1000 kcal.
Primary outcomes were total and cardiovascular mortality and
combined cardiovascular events. Combined cardiovascular events
included any of the following: cardiovascular deaths, cardiovascular
morbidity from non-fatal myocardial infarction, angina, stroke, heart
failure, peripheral vascular events, and atrial fibrillation, and unplanned
cardiovascular interventions like angioplasty and bypass surgery.
The meta-analysis did a comprehensive search of articles published
from March 1998 up to June 2010 using the Cochrane Library, MEDLINE,
EMBASE, CAB Abstracts, CVRCT Registry, SIGLE, bibliographies and
experts. The search resulted in 22,012 titles and abstracts which were
initially scanned for review, of which a total of 48 randomized controlled
trials were included in the review. There were no other large clinical
trials that were published from 2010 onwards that could be included in
this review.
Validation and appraisal of the meta-analysis showed that this was
of moderate methodological quality (Appendix Table 1). It included
randomized controlled trials that are of high quality evidence, and there
is certainty in the benefits of the treatment arms and control arms.

However, there was no cost analysis study conducted in the analysis
and there were questions of directness to our population. Most of the
studies were conducted in North America, with Caucasians comprising
most of the study subjects. Three studies were conducted in Australia/
New Zealand, and one study was conducted in the Middle East. None
of the randomized controlled trials were done on Filipinos as subjects.
Generally, the quality of the evidence ranged from moderate to high.
However, the quality of the evidence for two outcomes were graded low
as some of the clinical trials included in the analysis were not blinded
with different levels of attention and support to the intervention group.
It was also noted that there were fewer than 1,000 events in total so
there is limited power to estimate the effect. Ten of the comparison arms
included only people at high risk for cardiovascular disease, 17 were at
moderate risk, and 33 at low risk. Sixteen comparisons included only
men, 14 only women, and 30 comparison arms were both men and
women.
For the primary outcomes, reduction or modification of fat diets
showed no statistically significant effects on overall mortality (RR 0.98,
95% CI 0.93-1.04, I2=0.0%, n=71,790 participants, 4292 deaths) or
cardiovascular mortality (RR 0.94, 95% CI 0.84-1.04, I2=0%, n=65,978
participants, 1,407 cardiovascular deaths) compared to usual diet.
Reduction of dietary saturated fats, through reduction and/or
modification of dietary fat, is protective from the development of the
composite outcome of major cardiovascular events, reducing them by
14% (relative risk 0.86, 95% CI 0.77 to 0.96) based on 24 comparison
arms with 65,609 participants and I2 of 50%.The intervention reduced
the CV events in men, but not in women or in combined studies of men
and women. Studies in community settings also reduced cardiovascular
events if given the low fat/modified fat diet. The protective effect was seen
in patients who continue to modify their diet over at least two years. This
was given a grade of moderate because some of the studies included in
the review did not report any cardiovascular events. The importance of
this result should allow physicians to give dietary advice of reduction of
saturated fats to patients who are at high risk of cardiovascular disease
and should be stressed that this should be a sustained pattern of eating.
The studies in the meta-analysis also showed a modest reduction
in the serum total cholesterol (mean difference=-10.1 mg/dL; 95% CI
-18.2 to -1.54; 2,131 participants, I2 51%), serum LDL cholesterol (mean
difference=-8.1 mg/dL; 95% CI -13.5 to -3.1; 627 participants, I2 0%) and
fasting serum triglycerides (MD -23.9 mg/dL; 95% CI -46.9 to -0.00; 218
participants, I2 0%). However, there was no clear effect on serum HDL
Table 4. Summary of evidence on the effects of dietary modification

Outcome Evidence Relative Overall Overall Relative NNT
Quality Importance Control Rate Treatment Risk
Rate
Total Mortality High 9 2404/40957 1888/30833 0.98 NS
(0.93,1.04)
Cardiovascular High 9 774/37840 633/28138 0.94 NS
Deaths (0.85,1.04)
Fatal and non- High 9 1174/37280 894/27611 0.9 NS
fatal MI (0.72,1.11)
Strokes (Fatal High 9 683/34790 457/25063 0.99 (0.89, NS
and nonfatal) 1.11)
Cardiovascular Moderate 7 2867/37402 2020/28106 0.86 (0.77, 209
events 0.96)
Revascularization Moderate 6 NS NS NS NS
cholesterol.
Reduction or modification of dietary fat may be protective of
cardiovascular events, with a decrease in levels of total and LDL
cholesterol, and triglycerides. However, the trials showed no clear benefit
on overall mortality and cardiovascular mortality. Table 4 summarizes
the results of the review and the relevant outcomes.
The latest guidelines from the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines9
emphasized that lifestyle modification, particularly heart healthy diets,
remains a critical component of health promotion atherosclerotic
cardiovascular disease, both prior to and in concert with the use of
cholesterol-lowering therapy. The International Atherosclerotic Society10
released a position paper recommending a reduction of saturated fat
in the diet to <7%, decreasing trans fat by 1%, and dietary cholesterol
to < 200 mg/day of the daily total calorie intake. This is similar to
the recommendations of the National Institute for Health and Care
Excellence of the United Kingdom 2014.11
Simple Dietary Plan for Fat Modification
In the Philippines, the Food and Nutrition Research Institute (FNRI)
has developed a food pyramid, which is a simple and easy to follow
daily eating guide and is based on the daily food intake of Filipinos. A
comprehensive list of food menu was published in the 2005 Philippine
Practice Guidelines. Based on the food pyramid, the total fat intake is
only 15% of the total caloric intake, accounting for the low calorie intake.
It was advised in the FNRI food pyramid to increase fat intake by adding
margarine or butter in the diet, and some of the invisible oils found in
fruits and nuts.
In 2014, the FNRI released a simpler version of the food pyramid,
which they termed as “Pinggang Pinoy”or “Pinoy Plate” (Figure 5 and
Table 5). It used a science-based approach with the best scientific
evidence and compliments and supplements the food pyramid of the
FNRI. It serves as a reminder to Filipinos on how to fill up their plates
properly. A nine-inch plate is advised, and distributing foods proportionally
among the food groups provides approximately 1,200 to 1,500 calories
per day. It is advised that half of the plate is composed of green leafy
vegetables and one serving of fruit per meal. For fruits, 4 to 6 servings
are encouraged per day.
Figure 5. Pinggang Pinoy
Table 5. Guide to serving portions
Rice and alternatives 1 serving of any of the following:

• 1 cup cooked rice
• 4 pcs of pandesal (17 g each)
• 4 slices of loaf bread (17 g each)
• 1 cup of cooked macaroni or
spaghetti noodles
• 1 piece of root crop (e.g.,
kamote, kamoteng kahoy, gabi,
ubi)
Fish and alternatives Two servings of any of the following:

• 1 pc. of small fish (e.g.,
galunggong)
• 1 pc. Of small chicken leg or 1
matchbox size of chicken breast
• 1 matchbox size of meat (e.g.,
beef or pork)
• 1 pc. of small chicken egg
Vegetables • ¾ to 1 cup of cooked or raw

vegetables
Fruits 1 serving of any of the following:

• 1 medium-sized fruit (e.g.,
banana, dalanghita, kaymito) OR
• 1 slice of big fruit (e.g.,
watermelon, papaya)
Water and beverages 8 or more glasses of water daily
Addressing Malnutrition
Malnutrition due to low caloric and low protein intake is an important
public health problem in the Philippines, even among adults. Data from
the Food and Agriculture Organization reported that 17% of Filipino
adults are underweight for age.12 Malnutrition is also a major problem
among certain patient subgroups, such a chronically ill patients, where
the prevalence can exceed 70%.13 Malnutrition in these patients
adversely diminish outcomes. Data from NNHeS showed that one out
of ten (10.0%) adults have chronic energy deficiency (CED, BMI <18.5),
while three out of ten (31.1%) are overweight or obese.
Therefore, it is important to perform an overall assessment of
nutritional status in patients when advising about dietary changes.
Dietary advice should ensure that patients, even those with evidence
of cardiovascular disease, do not predispose the patient to caloric and
protein malnutrition. In underweight patients, majority of the caloric
intake comes from carbohydrates and proteins to ensure low fat intake.
A referral to a nutritionist or dietitian is recommended in all patients,
regardless of nutritional status, when accurate dietary advice is sought.
Statement 1.2 Smoking Cessation

For individuals at any level of cardiovascular risk, cigarette smoking
cessation is STRONGLY RECOMMENDED.
Summary of Evidence
Randomized controlled trials on smoking cessation and their effect
on cardiovascular morbidity and mortality were included in the review
for this recommendation. There are 1,355 clinical trials on smoking
cessation but, only three (3) trials had relevant outcomes and were thus
included. All three trials looked at primary prevention outcomes. Two
of the studies looked at multiple risk factors, such as diet and smoking
cessation, while the last one also included respiratory and cancer
outcomes.
The clinical trials included in the CPG are seen in the appendix.
Two clinical trials, MRFIT and OSLO study included men with multiple
risk factors, while the Lung Health Research Study Group had both men
and women in the study.14-16 The interventional group had an intensive
treatment program for smoking cessation, which include behavior
modification and may use devices such as nicotine gum or patches.
Table 6 summarizes the review and relevant outcomes. Statistically
significant results are seen in the total mortality (N=18,023; RR 0.90
[95% CI 0.82, 0.99)], and acute major CV events (N=18,023; RR 0.85
[95% CI 0.76, 0.95). There was a trend towards benefit of cigarette
cessation in CV mortality. Only one trial looked at secondary outcomes
such as MI and stroke, and the former outcome showed a trend in favor
of cigarette cessation.
The GRADE balance sheet seen in the appendix combines the
appraisal of the studies included in the guideline recommendation with
the outcomes. Generally, the quality of the evidence is moderate with
the downgrade due to the question of directness. The studies were all
Table 6. Summary of evidence on the effects of smoking cessation

Outcome Studies Participants Effect Estimate NNT
(RR, 95% CI)
102 fewer per
Total Mortality 3 18,023 0.90 [0.82, 0.99]
1000 (9.8)
Cardiovascular 2 fewer per
2 16,791 0.92 [0.76, 1.12]
deaths 1000 (500)
Fatal and
nonfatal NS
1 12,866 0.92 [0.80, 1.07]
myocardial
infarction
Cardiovascular 10 fewer than
3 18,023 0.85 [0.76, 0.95]
events 1000 (100)
Stroke NS
1 12,866 1.20 [0.79, 1.81]
done in Caucasian populations, and Asians, in particular Filipinos were

not part in these trials.
In conclusion, total cigarette smoking cessation is recommended to
patients with all levels of CV risk factors.
Use of electronic cigarettes as alternative to cigarette smoking and as a

smoking cessation aid
Electronic cigarettes are a form of Electronic Nicotine Delivery
Device. These products deliver doses of nicotine or non-nicotine vapors
to the respiratory system without the need for combustion of tobacco.
However, a position statement issued by the Philippine College
of Chest Physicians (PCCP) highlighted that there is profound lack of
evidence on the effectiveness of electronic cigarettes as a tool or aid to
smoking cessation.17 Furthermore, the health effects of these devices
are not known considering the lack of studies, while carcinogens and
other toxic chemicals at low levels were detected in the vapors. Thus,
PCCP does not support the use of these devices as smoking alternatives
or cessation aids until long-term efficacy and safety data have been
reported.
Statement 1.3. Exercise

For individuals at any level of cardiovascular risk, adequate exercise
is RECOMMENDED.
Table 7. Summary of evidence on the effects of exercise

(RR, 95% CI)
All cause mortality 2 6,027 0.95 [0.86, 1.05]

Cardiovascular 2 5,305 0.97 [0.85, 1.09]
mortality
MACE 2 5,305 0.75 [0.62, 0.91] 48
Non-fatal myocardial 1 160 0.29 [0.11, 0.76] 7
infarction
Stroke 2 5,305 0.88 [0.67, 1.17]
Summary of Evidence
Literature review revealed 48 articles that evaluated the benefit
of exercise on the risk of cardiovascular outcomes. Mostly were
observational and cohort studies. The lack of randomized controlled
trials was mostly attributed to poor long-term adherence to exercise
programs. Furthermore, only a few studies evaluated hard cardiovascular
outcomes. Thus, only four studies were included in the analysis: the
LOOK Ahead trial, the STENO2 trial, the Chengdu trial, and the study by
Fowler and colleagues (2002).18-22
In general, these studies recommended approximately 150 minutes
of moderate- to high-intensity exercise per week. Pooled analysis
revealed that such an exercise regimen reduced major acute coronary
events by 25%, and non-fatal myocardial infarction by 71% (Table 7).
Quality of evidence for the important outcome of major adverse
cardiovascular events was moderate, with an NNT of 48. Additionally,
exercise was found to marginally reduce LDL-C by 0.45%, triglycerides
by 0.23%, and increase HDL-C by 0.02%.
Thus, exercise of approximately 150 minutes of moderate- to high-
intensity exercise per week is recommended in individuals to improve
patients’ outcomes.
Exercise prescription
Compliance is one of the major difficulties when prescribing exercise
to patients. It is important to highlight that consistency and regularity are
important so that exercise becomes an integral part of a patient’s lifestyle.
One way to achieve this is to explain that the time allotted per week
should be split into several exercise sessions. In this case, 150 minutes
per week should be cumulated from around five sessions per week with
a duration of 30 minutes. This will also ensure that the exercise sessions
do not interfere with a person’s daily routines. Furthermore, physical
activity may be integrated into their daily routine, such as climbing of
stairs or brisk walking.
It is important to specify that the patient should exert moderate to
intense activity during exercise. A general rule is that they should have
difficulty speaking during the exercise. However, at the same time, they
should not be experiencing symptoms such as chest pain, difficulty of
breathing, or dizziness/syncope. Examples of exercises may include
swimming, jogging, brisk walking, stair-climbing, cycling, dancing, sports
activities, and supervised aerobic exercise programs. Slow exercises
such as yoga or tai chi may improve strength and flexibility, but may be
inadequate in intensity as the patient becomes physically stronger.
The physician should assess the functional capacity and overall
risk of patients before prescribing exercise. If assessment reveals that a
patient is physically incapable of safely performing moderate to intense
exercise, refer the patient for physical rehabilitation and strengthening
to a qualified physiatrist.
Clinical Question 2
CQ 2. Among non-diabetics without ASCVD but with multiple risk
This clinical question aims to give guidance to the use of cholesterol-
lowering treatment for primary prevention in patients with several
cardiovascular risk factors. These risk factors were identified based on
the clinical trials reviewed for the CPG.
Statement 2
For non-diabetic individuals aged ≥ 45 years with LDL-C ≥ 130 mg/
dL AND ≥ 2 risk factors*, without atherosclerotic cardiovascular disease,
statins are RECOMMENDED for the prevention of cardiovascular
events.
*Risk factors are: male sex, postmenopausal women, smoker,

hypertension, BMI > 25 kg/m2, family history of premature CHD,
microalbuminuria, proteinuria, and left ventricular hypertrophy.
*Patients who fulfill the criteria for the diagnosis of familial
hypercholesterolemia (see statement 6 on screening and lipid
monitoring for familial hypercholesterolemia) should be initiated therapy
for aggressive LDL-C lowering
Summary of evidence
Randomized controlled trials (RCT) evaluating statins in individuals
without atherosclerotic cardiovascular disease (ASCVD) with at
least a minimum duration of one-year follow-up were reviewed for
this clinical question. A total of 7 RCTs were included, with a minimal
number of diabetics evenly distributed in both arms (with the exception
of the MEGA and ASCOT-LLT which have 21% and 24% diabetics,
respectively) (Appendix 1.4).23-29 Trials whose entry criteria included the
presence of diabetes mellitus were evaluated in a different subgroup.
All of these trials either used total cholesterol (TC) and/or LDL-C as part
of their inclusion criteria, with the lowest levels seen in the JUPITER
trial, which were 168 mg/dl for TC and 94 mg/dL for LDL-C. Lipid profile
determination was repeated after 3 months and was done yearly until
the end of these studies. The average reductions in TC and LDL- C in
the clinical trials were 20% and 29%, respectively. The average age of
the trial participants was 58 years old with a range of 44 -71 years of
age.
As for the desired outcomes, statins in individuals without
ASCVD showed a significant reduction in all-cause mortality by 19%,
cardiovascular death by 33%, myocardial infarction (MI) by 39%,
stroke by 26%, cardiovascular (CV) events by 27% and coronary
revascularization by 29% (Table 8). Even if MEGA and ASCOT-LLT,
which have a modest number of diabetics, were excluded from the
analysis, all of these outcomes remained significant.
These trials enrolled mostly men with at least 1 other risk factor.
Based on the INTERHEART study, as the number of risk factor increases
in an individual, the incidence of a myocardial infarction increased as
well.30 Therefore, the TRC agreed that if an individual has 2 or more risk
factors, statin is recommended due to the fact that there were significant
reductions in the pre-specified outcomes.
The quality of evidence was mostly moderate owing to indirectness
in the enrolled population which mostly included Caucasians, with
the exception of the MEGA study, which enrolled Japanese patients
(Appendix 1 Table 1.4). The evidence on cardiovascular events as an
outcome was graded as low due to its issue of inconsistency with a large
I2 of 59% (this could be due to CV events being a secondary outcome in
all the trials with the exception of AFCAPS/TexCAPS). All the outcomes
were deemed critically important except for coronary revascularization,
which was important since it is an outcome least likely to happen if these
Table 8. Summary of Evidence on Treatment Effects of Statins in

Primary Prevention.
Outcome Studies Total Effect Estimate NNT
Participants (RR, 95% CI)
Total Mortality 4 42,534 0.81 (0.72-0.90) 167
CV death 7 50,450 0.67 (0.57, 0.79) 250
MI 7 50,450 0.61 (0.54, 0.70) 111
Stroke 6 43,845 0.74 (0.63, 0.88) 250
Cardiovascular 4 42,544 0.73 (0.67, 0.79) 56
events
Coronary 4 49,586 0.71 (0.65, 0.78) 100
Revascularization
individuals were treated optimally.

The TRC and Voting Panel decided to implement LDL-C and age
cut-offs to better target patients who have no evidence of atherosclerotic
disease but would benefit from statin therapy.
The LDL-C level chosen was from the ASCOTT-LLT trial, where
patients had a mean LDL-C of 131.3 mg/dL to represent patients
at higher risk of development of cardiovascular outcomes in light of
additional risk factors.
The recommended cut-off age of 45 years old was on the basis of the
epidemiology of dyslipidemia among Filipinos and the age consideration
of patients in the different primary prevention trials appraised. Forty-five
years was decided to be the representative age at which patients with
multiple risk factors for development of atherosclerotic cardiovascular
disease would benefit from statin therapy.
Lastly, the primary prevention trials on statins only included patients
with at least 2 risk factors. The TRC was not able to find data on patients
with one or no risk factors. Hence, the TRC recommendations only
encompass patients with 2 or more risk factors. It should be emphasized
that although the TRC has no recommendations for patients > 45 years
with less than 2 risk factors, individuals in this group are still eligible for
lifestyle interventions, as discussed in the previous section.
Thus, the use of statins for primary prevention of ASCVD is
recommended for patients aged 45 years and above with 2 or more risk
factors.
Comparison with other guidelines

The 2014 ACC/AHA guidelines recommend the initiation of statin
therapy for primary prevention in the following patient groups: 1)

individuals ≥21 years of age with LDL-C ≥190 mg/dL to achieve at least
a 50% LCL-C reduction; 2) all diabetic patients; and 3) patients with
more than 7.5% risk for development of ASCVD based on the ACC/AHA
cardiovascular risk calculator (provided with the published guidelines).9
In contrast, the 2011 ESC guidelines recommend the use of statins to
treat hypercholesterolemia to a level dictated by the patient’s calculated
risk score using the Systematic Coronary Risk Evaluation (ESC SCORE)
risk charts.31 Unfortunately, there is no local risk scoring that has been
developed for Filipinos to determine the risk for development of ASCVD,
and studies on the applicability of other risk scoring systems on Filipinos
have not been done.
Clinical Question 3
CQ 3. Among diabetic individuals without ASCVD, should statins be
recommended?
Statement 3
For diabetic individuals without evidence of atherosclerosis
(ASCVD), statins are RECOMMENDED for primary prevention of
cardiovascular events.
Summary of the evidence

Evidence on the use of statins for primary prevention of
cardiovascular outcomes were derived from 8 different clinical trials. In
the original guideline published in 2005, only 5 studies were included;
this has been updated in the current recommendation.
Of the eight studies that were included, five were sub-studies from
a larger group of individuals who had no previous cardiovascular events
(AFCAPS/TEXCAPS, ALLHAT-LLA, ASCOT-LLA, PROSPER, MEGA)
while the other three were primarily studies done on individuals with
diabetes (ASPEN, CARDS, HPS).25,26,32-37 Whenever a study involved
a combination of patients for primary and secondary prevention, then
only the data for primary prevention was obtained and analyzed (e.g.,
ASPEN).
Appendix 1 Table 1.4 summarizes the characteristics of the studies
that were included in this review. Different statins of various daily doses
were used including lovastatin 20-40 mg, pravastatin 10-20 and 40 mg,
atorvastatin 10 mg, and simvastatin 40 mg. The baseline lipid values
also varied across the studies with the mean baseline total cholesterol
ranging from 195 +31 to 227 +33.8 mg/dL; and the baseline mean
LDL-C ranging from around 115 +26.6 mg/dL to a high of 150 +31 mg/
Table 9. Summary of Evidence on Treatment Effects of STATINS in

Diabetic Individuals without ASCVD
(RR, 95% CI)
Total Mortality 1 2,837 0.73 (0.53,1.010) Ns
Fatal CHD/CV death 3 7,544 0.98 (0.68, 1.41) Ns
Fatal & Nonfatal MI 4 27,810 0.73 (0.64, 0.83) 100
Stroke 4 27,810 0.75 (0.63, 0.89) 200
Cardiovascular 8 16,095 0.78 (0.70, 0.86) 45
events
Coronary 3 25,783 0.84 (0.73, 0.97) 200
revascularization
dL. The studies included both genders, and the age range for most of the
studies is from 45 to late 70’s, with the PROSPER study being specific
for elderly 70-82 years.
Table 9 summarizes the results of the review and the relevant
outcomes. Statistically significant results are seen from the outcomes of
fatal and nonfatal MI (N=27,810, RR 0.73 [0.64, 0.83]), stroke (N=27,810,
RR 0.75 [0.63, 0.89]), acute major CV events (MACE) (N= 16,095,
RR=0.78 [0.70, 0.86]) and coronary revascularization (N=25,783, RR=
0.84 [0.73, 0.97]). A trend to benefit is seen for the outcomes of total
mortality, and CV death. Significant impact on clinical outcomes was
achieved using even low to moderate intensity statins.
The GRADE balance sheet combines the appraisal of the studies
included in the guideline recommendation with the outcomes. Generally,
the quality of the evidence is moderate with the downgrade due to
the question of directness. The studies were all done in Caucasian
populations and Asians, and in particular Filipinos were not included in
the samples that were included in these trials. Likewise, 5 out of the
8 studies were subgroup analysis of diabetic individuals from a larger
group of individuals with no previous cardiovascular events.
Thus, the recommendation is only moderate for the use of statins for
primary prevention in diabetic individuals without ASCVD.
Recommendation from other guidelines

Other guidelines have similar recommendations but add on a layer
of risk on top of diabetes mellitus. For example, the Canadian Diabetes
Association guidelines recommend statin therapy for diabetic individuals
with an indication for lipid-lowering therapy.38 The American Diabetes
Association on the other hand recommends high-intensity statin for

patients of all ages with diabetes and overt CVD, or for those who are
at least 40 years old and with additional CV risk factors (total of 3 risk
factors: > 40 years old, diabetes and another CV risk factor).39 Those
who have diabetes and are aged 40-75 years old should consider using
moderate-intensity statins. It is silent though for diabetic individuals who
are less than age 40.
The recommendations in this local guideline is to give statin therapy
for ALL adult diabetic individuals for primary prevention especially among
those with Type 2 diabetes mellitus, without regard for age nor duration
of diabetes. The justification for this recommendation is the frequent
observation that both macrovascular and microvascular complications,
as well as various CV risk factors are prevalent even among newly
diagnosed diabetics. For example, the CANDI Manila study among
newly diagnosed adults with type 2 diabetes mellitus (mean age of 50
years) demonstrated a high prevalence of diabetic complications and
CV risk factors.45 The electrocardiographic findings showed that 2%
had myocardial infarcts, 3% had ischemic changes, and 6% had left
ventricular hypertrophy. Hypertension was found in 42% of individuals
with a mean BP of 144/88 mm Hg, and 80% of all subjects had LDL-c
of at least 100 mg/dL, with another 38% with elevated triglyceride of at
least 150 mg/dL.
Clinical Question 4
CQ 4. Among diabetic patients without ASCVD, should fibrates be
recommended as an alternative to statin therapy?
Statement 4
See section on non-statin therapy
Clinical Question 5
CQ5. Among patients with established ASCVD, should statins be
given?
Statement 5
For patients with established atherosclerotic cardiovascular disease
(ASCVD), statin therapy is RECOMMENDED.

Evidence on the use of statins for the secondary prevention of
cardiovascular outcomes were derived from 18 clinical trials comparing
statins against placebo in secondary prevention populations.39,41-59
Table 10. Summary of Evidence on treatment effect of statins for

secondary prevention
Outcome Studies Total Effect Estimate NNT
Participants (RR, 95% CI)
General population
All cause 15 60,166 0.87 (0.83 – 0.91) 67
Mortality
CV death 14 59,949 0.79 (0.75 – 0.84) 62
Myocardial 13 54,018 0.70 (0.66 – 0.75) 45
infarction
Stroke 11 52,426 0.78 (0.72 – 0.84) 83
Patients with diabetes
Major Adverse 5 4,351 0.85 (0.79 – 0.91) 16
CV Events
Myocardial 5 1,091 0.73 (0.53 – 1.00) NS
infarction
Stroke 5 2,370 0.67 (0.49 – 0.90) 37
All-cause 5 707 0.78 (0.53 – 1.14) NS
mortality
Five studies assessed the use of statins for secondary prevention in

individuals with type 2 diabetes.33,60-63
Appendix 1 Table 1.5 summarizes the characteristics of the studies
that were included in this current guideline. Statin preparations available
locally were the only ones included in the review, which includes the
following statins; fluvastatin 80 mg, pravastatin 20 to 40 mg, atorvastatin
10 to 80 mg, and simvastatin 10 to 40 mg. The baseline lipid levels
in the included studies varied, with the mean baseline LDL-C ranging
from 199.3+39.0 mg/dL to 387.1+73.5mg/dL. The studies included both
genders.
Statin treatment in those with ASCVD resulted in a statistically
significant reduction in the critical outcomes of total mortality (RR 0.87;
95% CI 0.83-0.91), cardiovascular mortality (RR 0.79; 95% CI 0.75-
0.84), myocardial infarction (RR 0.70; 95% CI 0.66-0.75) and stroke
(RR 0.78; 95% CI 0.72-0.84), with NNTs ranging from 45 for myocardial
infarction, to 83 for stroke (Table 10). Hence, in patients with ASCVD,
statin therapy is recommended.
For those with DM, statistically significant results are seen for the
outcomes of MACE (RR 0.85; 95% CI 0.79 – 0.91) and stroke (RR 0.67;
95% CI 0.49 – 0.90) (Table 10).
Table 11. Statin treatment intensity

Treatment intensity % LDL-C reduction Drug regimen
Low intensity 20% - 30% Fluvastatin 20-40 mg
Pravastatin 5-40 mg
Simvastatin 10 mg
Moderate intensity 31% - 40% Atorvastatin 10 mg
Fluvastatin 80 mg
Rosuvastatin 5-10 mg
Simvastatin 20-40 mg
High intensity >40% Atorvastatin 20*-80 mg
Rosuvastatin 20-40 mg
Note: Modified from Stone et al: 2013 ACC/AHA guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation
The GRADE balance sheet for the appraisal of evidence on the use
of statins in secondary prevention among patients with ASCVD and DM
showed that the quality of evidence is moderate for both subgroups,
with the quality downgrade resulting from questions of directness.
The studies included were all performed on Caucasian populations.
Asians, particularly Filipinos, were not well-represented in these trials.
Heterogeneity of pooled studies also resulted in serious inconsistencies
and a further downgrade of the evidence.
Evidence on the appropriate statin intensity for secondary prevention
in individuals with ASCVD were obtained from 4 trials (Appendix 2 Table
2.8) that compared varying statin regimens: Armitage et al (2010), Phase
Z of the A-Z trial(2004), TNT (2005) and IDEAL (2005) clinical trials.63-66
These abovementioned studies compared high intensity (atorvastatin
80 mg or simvastatin 80 mg) to medium intensity (atorvastatin 10 mg
or simvastatin 20 mg) statins. High intensity statins reduce LDL-C by
>40%, compared to low intensity statins which reduces LDL-C by 20-
30%.
Analysis of the evidence on high-intensity vs moderate intensity
statin therapy using GRADE Pro showed that the quality of evidence
is moderate, with quality downgrade due to the question of directness.
Filipinos where not well represented in the clinical trials, and were mostly
done in Caucasians. The evidence was able to show a net benefit
favoring high-intensity statin therapy in reducing the critical outcome
of myocardial infarction (RR 0.85; 95% CI 0.78-0.92).
This updated guideline recommends that high-intensity statin
therapy be used in secondary prevention of patients diagnosed with
ASCVD. It should be emphasized that the definition of statin treatment
intensity rests on the degree of LDL-C reduction, and less on the drug
dose used. There are some evidences that Asians may require a lesser
*According to a study by Wu, et al, J Formos Med Assoc 2002(superscript 67), Ator 20 mg can reduce
LDL by 42.5% in Asians, including Filipinos
dose to achieve target LDL-C goals, and using high dose statins may
lead to higher risk of developing adverse drug reactions. One trial
looking at the efficacy of simvastatin and atorvastatin 20 mg once daily,
which included Filipinos, reduced LDL-C levels by 34.8% and 42.5%
respectively; however, the sample size is small.67 Thus, there is a need
to conduct a bigger clinical trial for Filipino patients. The TRC decided
to retain the table on statin intensity to be used for Filipino patients for
secondary prevention (Table 11) and LDL-C reduction as applicable to
our population. Needless to say, we also recommend to individualize
treatment in patients who may develop intolerance to high dose statins,
that physicians use appropriate statin dose that will achieve the needed
treatment reduction goal but will also minimize the risk of adverse events.
Statin Treatment Goal

In general, the 2015 CPG recommends a 30% or greater reduction
in LDL-C for appropriate treatment goal with statin therapy, as trials
on moderate- vs high-intensity statin therapy have shown a dose-
dependent response in terms of benefit in the reduction of adverse
outcomes. However, for purposes in clinical practice, a treatment goal
LDL-C level of < 70 mg/dL may be recommended, as adapted by some
international guidelines.

Several international guidelines have their own recommendations for
managing patients with established ASCVD. The 2011 European Society
of Cardiology (ESC) guidelines on dyslipidemia recommend statins at the
highest tolerable dose as part of the interventions for patients with very
high cardiovascular risk, including those with established cardiovascular
disease.31 The 2012 Canadian Cardiovascular Society guidelines
likewise recommend statins for those with high risk (e.g., those with
clinical vascular disease or those with Framingham Heart Risk score
>20%).68 Treatment is focused on achieving target serum lipid levels,
and dose is adjusted accordingly to this end. On the other hand, the
2013 American Heart Association/American College of Cardiology (AHA/
ACC) guidelines recommend that high-intensity statin therapy should be
initiated or continued as first-line therapy in those 75 years of age or
younger who have clinical ASCVD, unless contraindicated.9 Moderate-
intensity statin therapy is indicated only in those who cannot tolerate
high-intensity statin therapy. Judicious use of statins after consideration
of benefits and risks is recommended for those with clinical ASCVD
aged over 75 years.
Clinical Question 6
CQ 6. Among patients with ASCVD, should fibrates be given as an
alternative to statins?
Statement 6
See section on Non-statin therapies.
Clinical Question 7
CQ7. Among patients with acute coronary syndrome (ACS), should
statin therapy be given?
Statement 7
For individuals with acute coronary syndrome, early high-intensity
statin therapy is RECOMMENDED and should be continued when
already on statin therapy.
Summary of Evidence
Timing of therapy is critical among patients with acute coronary
syndrome. Early intervention is advocated to optimize recovery and
minimize complications. The adage “time is muscle” is based on the
principle of the necessity for immediate action during the golden period
in which myocardial ischemic damage is still potentially reversible or
myocyte necrosis can still be contained and much of the myocardium
in the ischemic penumbra can still be salvaged. This new guideline
statement focuses on the timing of initiation (or continuation) of statin
therapy among patients diagnosed with acute coronary syndrome
(ACS).
Among randomized controlled trials on early statin therapy for acute
coronary syndrome, ten trials were adjudicated to be included in the
analysis of initiation of statins falling within the first 5 days after an acute
coronary event and that total mortality, cardiovascular death, myocardial
infarction, major cardiovascular events, revascularization, and stroke
are reported. These ten trials are A to Z, PACT, MIRACL, Musashi-AMI,
LAMIL, PTT, ESTABLISH, LIPS, PAIS, and FACS.64,69-77
Table 12 summarizes the results of the review and the relevant
outcomes. Statistically significant results are seen from the outcomes
of total mortality, CV death, stroke and major cardiovascular events.
A trend to benefit was seen for the outcomes of non-fatal myocardial
infarction and revascularization. This pooled analysis shows that statins,
when initiated early within 5 days of ACS, results in fewer total deaths,
cardiovascular deaths, stroke and major cardiovascular events, with a
Table 12. Summary of Evidence in the use of statins in Acute

Coronary Syndrome
(95% CI)
Total Mortality 10 13,707 0.80 (0.67-0.94) 110
CV death 8 10,465 0.74 (0.58-0.94) 125
Non Fatal Mi 10 13,707 0.93 (0.81-1.08 NS
Stroke 10 13,707 0.70 (0.50-0.99) 227
Cardiovascular 10 13,707 0.88 (0.82-0.94) 43
event
Revascularization 10 13,707 0.95 (0.86-1.06) NS
trend towards reduction of myocardial infarction, and revascularization.

The quality of evidence of some studies is moderate based on
the GRADE Pro Evidence Table (Appendix 2 Table 2.11) with the
downgrade due to the question of directness, i.e. these studies included
Caucasians, and Filipinos were not well represented. The Musashi-AMI
and ESTABLISH trials were carried out in a Japanese population. For
non-fatal myocardial infarction and revascularization, the quality of the
studies was low due to the question of directness and imprecision (wide
confidence interval). For major cardiovascular events, the quality of
evidence was low due to downgrading for directness and inconsistency
(I2=60).
Thus, in patients with atherosclerotic cardiovascular disease, statin
therapy is recommended with low to moderate level of evidence for
improving critical outcomes. Considering the severity of acute coronary
syndrome and the dose-dependent effect of statins, high-intensity is
recommended in this extremely high-risk group.

Published guidelines on the diagnosis and management of acute
coronary syndrome incorporate general assertions with respect to the
temporal aspects of statin therapy. In the 2014 version of the Philippine
Heart Association Clinical Practice Guidelines for the Diagnosis and
Management of Patients with Coronary Artery Disease, starting statins
is strongly recommended for all patients with Non-ST elevation acute
coronary syndrome.78 For those with ST Elevation Acute Coronary
Syndrome, three statements were made: 1) high-dose statins are
recommended during the first 24 hours of admission; 2) atorvastatin or
rosuvastatin are recommended during the early phase of therapy up
to at least four weeks; and 3) high-dose rosuvastatin (20 to 40 mg) or

atorvastatin (40 to 80 mg) therapy is recommended before emergency
percutaneous coronary intervention. Comparing the local guidelines
to the 2014 AHA/ACC Guideline for the Management of Patients With
Non–ST-Elevation Acute Coronary Syndromes, initiation or continuation
of high-intensity statins is a Class I Recommendation with Level of
Evidence A.79 In the 2013 ACC/AHA Guideline for the Management of
ST-Elevation Myocardial Infarction, initiation or continuation of high-
intensity statin therapy is a class I recommendation but with Level of
Evidence B.80 These aforementioned guidelines are congruent and
clearly advocate for the early initiation or maintenance of statin therapy
across the spectrum of acute coronary syndrome.
Clinical Questions 8
CQ8. Among patients with established ASCVD or diabetes, should
Among patients without ASCVD but with multiple risk factors, should
Statements 8
For individuals with evidence of ACSVD or diabetes, the use of the
lipid profile is RECOMMENDED for monitoring of treatment response
since ALL patients with ASCVD should be on lipid-lowering therapy.
For individuals without evidence of ASCVD but aged > 45 years
AND with 2 or more risk factors*, the use of lipid profile for screening is
RECOMMENDED.
For individuals on lipid-lowering therapy, the use of lipid profile for
monitoring of treatment response is RECOMMENDED.
* Risk factors are: male, postmenopausal women, smoker,

hypertension, BMI > 25 kg/m2, family history of premature CHD**,
microalbuminuria, proteinuria, and left ventricular hypertrophy.
**Patients who fulfill the criteria for the diagnosis of familial
hypercholesterolemia (see section on screening for familial
hypercholesterolemia) should be initiated therapy for aggressive LDL-C
lowering
It is essential to identify populations at risk and population to whom
treatment is recommended. Aside from identifying these populations,
monitoring the response to both pharmacologic and non-pharmacologic
therapy should be carried out in order to determine the magnitude of
treatment response and if the goal of treatment is achieved.
Lipid determination in secondary prevention

In the different clinical trials presented among secondary prevention
population (see CQ5), the use of statins versus placebo was beneficial in
the prevention of the following critical outcomes, namely: total mortality,
myocardial infarction, stroke and cardiovascular death. The NNTs per
1,000 individuals for the significant beneficial outcomes were 15 for
total mortality, 11 for stroke, 22 for MI and 16 for CV death (Section 6,
Table 2). In the five studies involving diabetics with ASCVD, the use of
statins versus placebo was beneficial for four critical outcomes, namely:
major cardiovascular events, myocardial infarction, stroke and all-cause
mortality. The NNTs per 1,000 individuals for the significant beneficial
outcomes were 62 for major cardiovascular events, 39 for myocardial
infarction, 27 for stroke and 32 for all-cause mortality. The significant
reduction of the outcomes mentioned was achieved after 1 to 5 years of
treatment with statins.
Since treatment is recommended among patients with ASCVD with
or without diabetes, regardless of lipid levels, lipid profile determination
is not necessary for screening but for monitoring therapeutic response
since ALL patients should already be on treatment. The role of the lipid
profile lies in its ability to determine the percent reduction or the level
of LDL achieved after six weeks of treatment to 3-6 months thereafter.
The time to achieve target levels based on the trials ranged from 1 to 8
years.
Lipid monitoring in diabetics in primary prevention

The use of statins versus placebo was beneficial in the prevention
of a critical outcome of fatal and nonfatal MI and four important
outcomes, namely: stroke, acute major CV event (MACE) and coronary
revascularization. The NNTs per 1,000 individuals for the significant
beneficial outcomes were 5 for stroke and coronary revascularization,
10 for fatal and nonfatal MI and 21 for MACE. In the trials, the treatment
commenced with lowest mean baseline total cholesterol and lowest
mean baseline LDL-cholesterol were 195 +31 mg/dL and 115 +26.6
mg/dL, respectively. The range of diabetic individuals treated for statins
was from 45 to 82 years (PROSPER study).37 Use of fibrates was not
recommended. However, similar to patients with ASCVD, screening
may not be necessary to commence treatment in this subset of patients,
since regardless of lipid levels and age, reduction of critical and important
outcomes is achieved with use of statins. However, monitoring of lipid
levels should be monitored for two reasons, namely: 1) to determine
the direction and magnitude of treatment response, and 2) to determine
the triglyceride level since it is an indirect measure of the adequacy
glycemic control and typically, improvements in the glycemic control can

also lead to improvements in the triglyceride level.
If the repeat levels are still below the desired reductions or LDL-C
level, intensification of lifestyle modification and pharmacologic therapy
is warranted. Statins can then be increased to the maximal dose
tolerated.
Lipid monitoring in patients with Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant
disorder of a mutation in the low-density lipoprotein receptor (LDL-R)
gene resulting in elevated LDL-C levels (typically, a level above 190
mg/dL should raise clinical suspicion, although wide ranges have been
reported). It has a prevalence of 1 in 500 Caucasians but currenty
there are no true estimates of people diagnosed with FH in Asia.81 To
date there is only one study involving Filipinos.82 Affected individuals
are at increased risk for cardiovascular events and premature coronary
artery disease, so early detection is deemed crucial for the initiation of
aggressive lipid-lowering therapy once diagnosis is made.
Several guidelines provide the standard diagnostic criteria for
patients with FH namely the Dutch Lipid Network Criteria (DLN), the
Simon Broome Register (SBR) and the Make Early Diagnosis to Prevent
Early Deaths (MEDPED) project. For practical applicability in our setting,
the DLN criteria (Table 13) should be used since it relies heavily on
clinical history and physical exam findings. However, the problem with
the use of DLN criteria is the limited availability of genetic testing.83
Due to the high cardiovascular risk of these patients, the lipid
profile should be carried out initally as screening (patients with FH have
LDL-C levels > 190 mg/dL) then subsequently for monitoring treatment
response since ALL patients with FH shoud be on aggressive LDL-C
lowering therapy.
Lipid determination in primary prevention

For individuals without evidence of ASCVD who are ≥ 45 years old
and with 2 or more risk factors, the use of lipid profile for screening
is recommended. In the seven different clinical trials included among
primary prevention population, the use of statins versus placebo was
beneficial in the prevention of the following critical outcomes, namely
all-cause mortality, cardiovascular death, myocardial infarction, stroke,
cardiovascular events and coronary revascularization. The NNTs
per 1,000 individuals for the significant beneficial outcomes were six
for all-cause mortality, 5 for cardiovascular death, 9 for myocardial
infarction, 4 for stroke, 18 for cardiovascular events, and 11 for coronary
Table 13. Dutch Lipid Network criteria on the diagnosis of

heterozygous familial hypercholesterolemia83
CRITERIA POINTS
Family history
First-degree relative with known premature* coronary and 1
vascular disease, OR
First-degree relative with known LDL-C level above the 95th
percentile
First-degree relative with tendinous xanthomata and/or arcus 2
cornealis
OR
Children aged less than 18 years with LDL-C level above the 95th
percentile
Clinical history
Patient with premature* coronary artery disease 2
Patient with premature* cerebral or peripheral vascular disease 1
Physical examination
Tendinous xanthomata 6
Arcus cornealis prior to age 45 years 4
Cholesterol levels mg/dl (mmol/liter)
LDL-C > 330 mg/dL (>8.5) 8
LDL-C 250 – 329 mg/dL (6.5–8.4) 5
LDL-C 190 – 249 mg/dL (5.0–6.4) 3
LDL-C 155 – 189 mg/dL (4.0–4.9) 1
DNA analysis
Functional mutation in the LDLR, apo B or PCSK9 gene 8
Diagnosis (diagnosis is based on the total number of
points obtained)
Definite Familial Hypercholesterolemia >8
Probable Familial Hypercholesterolemia 6-8
Possible Familial Hypercholesterolemia 3-5
Unlikely Familial Hypercholesterolemia <3
* Premature: < 55 years in men; < 60 years in women
LDL-C; low density lipoprotein cholesterol; FH, familial hypercholesterolemia; LDLR,
low density lipoprotein receptor; Apo B, apolipoprotein B; PCSK9, proprotein convertase
subtilisin/kexin type 9.
revascularization. All the trials included in the analysis used total

cholesterol (TC) and/or LDL-C as part of the inclusion criteria, with the
lowest TC and LDL-C levels of 168 mg/dL and 94 mg/dL coming from
the JUPITER trial.29 The range of LDL-C in the trials was 108 to 192 mg/
dLwith a mean 155 mg/dL. The average age of patients in the trials was
58 years old (range: 44-71 years).
In the ACS registry conducted by the Philippine Heart Association,
the LDL-C levels of Filipinos having acute myocardial infarction was
low and a percentage of them were already on statin treatment—
this may imply a residual risk.3 Since the lowest LDL-C level in
which treatment was commenced approximated 135 mg/dL, and
the approximate age in which treatment was likewise started was at
least 45 years old, determination of lipid profile as a screening tool is
necessary to determine baseline levels and to determine who among
patients without ASCVD will benefit from statin treatment.
Moreover, lipid profile determination is also needed to monitor
treatment response. In the trials on primary prevention, the average
reduction of TC and LDL-C was 20% and 29% respectively with a
minimum duration of 1 year (range: 1.9 to 5 years) for benefit to be
achieved. Lipid profile determination was done after 3 months of
treatment and yearly thereafter. Lastly, based on the trials, monitoring
of lipid profile after 3 months of treatment is also recommended to
determine achievement of treatment goals.
To guide clinicians, Figure 6 outlines a proposed algorithm for the
screening and treatment of patients.
Monitoring for adverse drug reactions

Long-term treatment of dyslipidemia may bring about concerns for
adverse drug reactions such as myalgias, myopathies and elevations of
liver function tests.
Baseline measurement of hepatic transaminase levels (alanine and
aspartate aminotransferase) should be performed before initiation of statin
therapy in patients at risk for developing liver injury.84 Serial liver function
test monitoring in asymptomatic individuals are not recommended.
However, should testing reveal elevations in transaminase levels during
the course of statin therapy, the recommended course of action is
outlined in Figure 7.
Statin-induced Myopathy
Statin myopathies are classified as either myalgias, myopathies,
myositis, or rhabdomyolysis (Table 14). In patients at risk for development
of statin myopathies, baseline creatine phosphokinase and subsequent
monitoring should only be performed when symptoms are present.
The TRC recommends a localized management algorithm for statin-

treated patients with muscle symptoms (Figure 8).
Finally, statins use is associated with a very modest excess risk
of new-onset diabetes (i.e., around 0.1 and 0.3 excess cases per 100
individuals treated for 1 year with moderate-intensity and high-intensity
statin therapy, respectively.) This risk seems to exist only in those with
risk factors for diabetes. Continuation of statin therapy is recommended
Figure 6. Screening and treatment algorithm for the management

of dyslipidemia
Legend:
* Risk factors: male, smoker, hypertension > 140/90 mmHg, BMI 25 kg/m2, family history
of premature coronary heart disease, proteinuria, left ventricular hypertrophy and post
menopausal women
** The guideline recommends high intensity dose of statins to reach target
** Treatment goal is to reduce LDL-C by >30%, or < 70 mg/dl
Note: If the patient is suspected or considered to have Familial

Hypercholesterolemia (FH) based on the Dutch Lipid Network score, lipid profile
is used for screening and monitoring of effect of treatment.
Table 14. Classification of statin myopathies

Myalgia Myopathy Myositis Rhabdomyolysis
ACC/AHA Focal or
Muscle Severe muscle
NHLBI diffuse muscle
Any disease of pain damage with
aches or
muscle with CK damage to
weakness with
elevation another organ
normal CK
(i.e., kidney) and
NLA CK > 10 x ULN
Myalgia with
US FDA CK > 10x ULN CK >50x ULN +
organ damage
ACC/AHA, American College of Cardiology/American Heart Association; NHLBI, National
Heart, Lung, and Blood Institute; NLA, National Lipid Association; FDA, Food and Drug
Administration; CK, creatine kinase; ULN, upper limit of normal.
Figure 7. Algorithm for Patients who are on Statins with Elevated

Liver Enzymes
Legend
ALT – alanine aminotransferase; AST – aspartate aminotransferase; ULN – upper limit of
normal
*If symptoms recur after multiple statin use at multiple dosing, may use non-statin therapy
(fibrates or ezetimibe)
Figure 8. Algorithm for Statin-induced Myopathy
in these patients due to their increased risk of ASCVD. The lowest NNT
to achieve benefits from statins is 43 compared with a NNH (harm) of
around 250.85
Clinical Question 9
Among patients with ASCVD, should omega-fatty acids be given as
an alternative to statin treatment?
Statement 9
See Section on Non-statin therapy
Table 15. Summary of study outcomes for the use of fibrates

versus placebo among individuals with ASCVD
(RR, 95% CI)
Total Mortality 2 2926 0.90 (0.76, 1.08)
Fatal CHD/CV 1 4662 0.89 (0.69, 1.15)
death
Nonfatal MI 1 2531 0.80 (0.65, 0.97) 34
CHD death 1 2531 0.79 (0.61, 1.02)
Stroke 1 2531 0.76 (0.55, 1.07)
Coronary 1 2531 0.93 (0.80, 1.08)
revascularization
Non-statin Therapy
Use of Fibrates in non-diabetic individuals with established ASCVD

Among patients with established ASCVD, fibrates are NOT
RECOMMENDED as an alternative to statins.
Summary of Evidence
The evidence on fibrates was taken mainly from the Veteran’s Affairs
High-density lipoprotein Intervention Trial (VA-HIT) and a subgroup of
patients with pre-existing ASCVD in the Effects of long-term fenofibrate
therapy on cardiovascular events in 9795 people with type 2 diabetes
mellitus (FIELD) study.86,87 The LOCAT study also contributed a small
number of patients.88 In the 2006 guidelines, the study on bezafibrate
was included in the analysis. In this update, bezafibrate study was
not included because it is not locally available. In VA-HIT, gemfibrozil
reduced nonfatal myocardial infarction (OR 0.77 [95% CI 0.61, 0.97])
and cardiovascular events (OR 0.73 [95% CI 0.6, 0.88]) among 2,531
men with coronary heart disease, a HDL-C of 40 mg/dL or less, and
an LDL-C level of 140 mg/dL or less. There was no effect on all-cause
mortality, stroke, CHD death and revascularization. In the FIELD study,
22% of both fenofibrate and placebo arms have prior cardiovascular
diseases. Among these patients, the authors reported cardiovascular
event rates of 25.5% in the fenofibrate group and 25.1% in the placebo
group. This is the only outcome reported under the specific subgroup of
patients with ASCVD (Table 15). In the LOCAT study, no mortality was
noted during the study for either arm.
The GRADE Pro balance sheet (Appendix 2 Table 2.10) shows the
quality assessment of the evidence on the use of fibrates in secondary
prevention. Generally, the quality of the evidence is low with the
downgrade due to the question of directness. The studies were all done
in Caucasian populations and Asians, and in particular Filipinos were
not included in the samples that were included in these trials. A second
downgrade was given for indirectness since the populations included
were not statin-intolerant patients. Thus, given the very low quality of
evidence, fibrates are not recommended as an alternative to statin
therapy in patients with established ASCVD.
Use of Fibrates on diabetic individuals without established ASCVD

For diabetic individuals without evidence of ASCVD, fibrates are
NOT RECOMMENDED as an alternative to statin for the primary
prevention of cardiovascular events.

Evidence on the use of fibrates for primary prevention of
cardiovascular outcomes were derived from 4 different clinical trials: the
SENDCAP (1998), DAIS (2001), FIELD (2005) and HHS (1987).87,89-92 In
the original guideline published in 2006, only 2 studies were included;
this statement updates the previous recommendations. Two of the
four trials (FIELD and DAIS) are combined primary and secondary
prevention studies on diabetic individuals. For FIELD, 22% of the trial
subjects had a history of previous cardiovascular disease. Data from
the primary prevention aspect of the trial could not be separated from
the rest of the subjects and hence, was reported as a combined total of
all patients with and without history of CV disease.For DAIS, 48% of the
study subjects also had a history of CV disease whose data could not be
extracted apart from the main trial results.2Hence, the full data set was
also reported.
In the review of literature, there were two other trials on the use
of fibrates among diabetic individuals: the BIP (2000) and VA-HIT
(2002).86,93 However, since these were purely secondary prevention
trials, they were not included in the meta-analysis nor the GRADE PRO
review.
In the end, only three trials were included in the analysis: SENDCAP
(1998), DAIS (2001), and FIELD (2005). HHS study was excluded not
only because it had a very small subgroup of patients with diabetes (N=
135, representing 3% of the total number of volunteers) but also because
it reported a composite outcome of myocardial infarction and CV death,
which was not one of the outcomes that were included in this guideline.
Table 16. Summary of Evidence on the use of Fibrates Among

Diabetic Individuals.
(RR, 95% CI)
Total Mortality 3 10,377 1.09 (0.94 to 1.26) NS
Cardiac mortality 3 10,377 1.09 (0.86 to 1.37) NS
Stroke 1 9,795 RR 1.1 (0.87 to 1.4) NS
Major Adverse 3 10,377 RR 0.85 (0.73 to 0.98) 100
Cardiovascular
Events
Data from the HHS revealed that the incidence of the combined outcome
of MI and cardiac death is 2/59 (3.4%) for the treatment (gemfibrozil)
group and 8/76 (10.5%) for the placebo group for a RR of 0.32.
Of the six outcomes that were considered (total mortality, CV deaths,
fatal and non-fatal MI, stroke or CVD, coronary revascularization and
major adverse cardiovascular events), only four were investigated as
outcomes by the clinical trials on fibrates. The outcomes of fatal and
non-fatal MI, as well as coronary revascularization were not investigated
by the fibrate trials.
The pooled data for each of 3 of the single outcomes (total mortality,
CV deaths and Stroke) did not show any statistically significant results
in favor of fibrates (Table 16). It was only for the composite outcome of
MACE where there was a small, statistically significant result in favor of
fibrates with an RR 0.85 (0.73,0.98) and NNT of 100.
GRADE PRO evaluation of evidence quality for each outcome
(Appendix 2 Table 2.9) showed that the quality of evidence for the
significant outcome was low, based on the lack of a Filipino population
(applicability) and the inclusion of small studies (DAIS and SENDCAP)
that contributed to imprecision. None of the trials involved Asians
specifically Filipinos.
Thus, for primary prevention in diabetic individuals without ASCVD,
fibrates are not recommended.
Until more data are available, there appears to be no evidence to
recommend routinely adding fibrates to statins once LDL-cholesterol
goals have been reached. It may be considered among men with high
baseline TG and low HDL-C once LDL-C has been reached.

The recommendations for the use of fibrates in this guideline are
similar to other guidelines, in that the principal drug for the primary
Table 17. Summary of Evidence in the use of PUFA among

Individuals with ASCVD
(RR, 95% CI)
Total Mortality 4 15,371 0.91 (0.84, 0.99) 62
Fatal CHD/CV 2 12,710 0.82 (0.63, 1.08)
death
Stroke 3 15,211 1.19 (0.97, 1.45)
Major 3 8,388 0.87 (0.65, 1.17)
Coronary 1 2,501 0.97 (0.79, 1.20)
revascularization
prevention of cardiovascular outcomes should be statins. The statin

dose should be optimized to reach the LDL goal of less than 100 mg/
dL for most diabetic individuals, and an optional target of < 70 mg/dL for
diabetics without previous CV events but who may be high risk for CV
outcomes because of established CAD.
The Canadian Diabetes Association (CDA) recommends the use of
statins as first line therapy to achieve an LDL goal of < 2.0 mmol/L.38
Similar to other people, fibrates may be given among diabetic individuals
as primary treatment when the TG > 10.0 mmol/L (approximately 880
mg/dL) to prevent pancreatitis (in some guidelines even for TG > 500
mg/dl). The CDA further states that in patients achieving target LDL-C
with statin therapy, the routine addition of fibrates or niacin for the sole
purpose of further reducing cardiovascular risk should not be used
(Grade A Level 1A). For individuals not at LDL-C target despite statin
therapy as described, a combination of statin therapy with second-line
agents (which may include bile acid sequestrants, cholesterol absorption
inhibitors, fibrates and nicotinic acid) may be used to achieve the LDL-C
targets; this is however, a Grade D recommendation based on the
consensus of their panel of experts.
Thus, fibrates for primary prevention among diabetic individuals
without prior ASCVD is not recommended since no statistically significant
effect was found for the critical outcomes of total mortality, cardiovascular
deaths, and strokes or cerebrovascular disease based on moderate
quality data. Fatal and non-fatal MI, and coronary vascularization was
not collected separately as an outcome among the clinical trials on
fibrates. It was only for major adverse cardiovascular events (MACE)
that is a composite outcome where a small statistically significant effect
of fibrates was found, but this was based on low quality evidence.
Use of Omega-3 Fatty Acid

For patients with evidence of ASCVD, poly-unsaturated fatty acid
(PUFA) or omega 3 fatty acid is NOT RECOMMENDED as an alternative
to statins for the secondary prevention of cardiovascular events.

The evidence was taken from pooled analysis of five studies.94-98
Studies included were randomized controlled trials comparing PUFA of
at least 1 g versus placebo for secondary prevention of cardiovascular
events.
In the GISSI HF study, 50% of heart failure causes are ischemic, but
data pertaining to this specific population is not available in the study.95
Two studies also included patients taking statins but the population
from both intervention and placebo groups are comparable and did
not significantly affect the heterogeneity and most of the outcomes.96,97
Two of the five RCTs are open label studies, thus increasing the risk of
bias.94,96
All-cause mortality was decreased by PUFA (RR 0.91 [0.84,0.99]),
but there was no effect on CV deaths (0.82 [0.63, 1.08]), nonfatal MI
(0.89 [0.70, 1.13]), MACE (0.87 [0.65, 1.17], stroke (1.19 [0.97, 1.45])
and revascularization (RR 0.97 [0.79, 1.20]).
The GRADE PRO balance sheet (Appendix 2 Table 2.12) shows the
quality assessment of the evidence on the use of PUFA in secondary
prevention. Generally, the quality of the evidence is low with the
downgrade due to the question of risk of bias and directness. The
studies were all done in Caucasian populations and Asians, and in
particular Filipinos were not included in the samples that were included
in these trials. Thus, due to the low quality of evidence, PUFA is not
recommended for the secondary prevention of cardiovascular events.
Combination Therapies
The TRC and the voting panel are in agreement that combination
therapy of a non-statin therapy (eg: omega 3 FA, ezetimibe, fibrates)
and a statin may allow for a greater degree of LDL-C reduction and
results in achievement of goal attainment for primary and secondary
prevention.
A recently published trial on the use of the combination of ezetimibe
plus statin treatment, the IMPROVE-IT, demonstrated that the
combination of 40 mg of ezetimibe and 10 mg of simvastatin in patients
hospitalized for acute coronary syndrome may be beneficial.99 Included
patients had an LDL-C of 50 to 100 mg/dL if on lipid-lowering therapy, or

50 to 125 mg/dL if not on lipid-lowering therapy. After the 7-year follow-
up, patients on the combination reached a mean LDL-C of 53.7 mg/dL
vs 69.5 mg/dL in those on simvastatin alone (p<0.001). Furthermore,
patients on the combination therapy had a 3.7% risk reduction in the
primary endpoint of combined outcome of cardiovascular death, nonfatal
myocardial infarction, unstable angina requiring rehospitalization,
coronary revascularization (≥30 days after randomization), or nonfatal
stroke (32.7% vs 34.7%; p=0.016). NNT was 50. Based on this new data
from the trial, the combination of ezetimibe and simvastatin may provide
marginal benefit in post ACS patients.
The issue on combining fibrates and statins is answered directly by
the ACCORD lipid trial.41 This study randomly assigned 5518 patients
with type 2 diabetes who were being treated with open-label simvastatin
to receive either masked fenofibrate or placebo. The primary outcome
was the first occurrence of nonfatal myocardial infarction, nonfatal
stroke, or death from cardiovascular causes with the mean follow-
up was 4.7 years. The ACCORD Lipid trial showed that there is no
evidence to administer fenofibrate to be routinely added to a statin for
the treatment of dyslipidemia in patients with type 2 diabetes mellitus.
The pre-specified subgroup analysis showed heterogeneity in the
treatment effect according to sex, with a benefit for men and possible
harm for women. However, adding fenofibrates to statin may have a
possible benefit for patients with both high baseline triglyceride level and
a low baseline level of HDL cholesterol.
The combination of niacin and statin was investigated in two clinical
trials, the AIM-HIGH and HPS2 THRIVE trials;100,101 however, since the
drug is not available in the Philippines, these were not appraised by the
TRC. Both clinical trials showed no benefit in combination therapy of
niacin and statin.
Therefore, the TRC recommendation is to attempt LDL-C reduction
using statin therapy first. If the patient cannot attain the LDL-C goal
Table 18. Lipid-lowering Effect of Non-statin therapies that are

Available in the Philippines
Non-statin % Change in % Change in % Change in
therapy Triglycerides LDL-C HDL-C
Fibrates 20%-50% decrease 5%-20% decrease 10%-20% decrease
Omega-3 20%-50% decrease 5%-10% increase 1%-23% increase
fatty acids
Ezetimibe 0-7%% decrease 18% decrease 1%-1% increase
recommended by the 2015 Guideline with statin monotherapy either

because of an intolerance to the necessary dose of statin, then other
locally available therapies may be combined.
Table 18 shows the estimated effect of currently available non-statin
therapies on lipid parameters.
HDL lowering therapies

The controversy between HDL cholesterol and CVD continues to
exist. Plasma levels of HDL-C is inversely related with the incidence of
coronary heart disease, as HDL exert several functions in the body such as
anti-inflammatory effects, antioxidative functions, improved endothelial
functions and improved insulin sensitivity.102 These pleiotropic effects
might lead to clinically significant improvements in the cardiovascular
health of patients. As seen in the NNHeS data above, Filipinos have
very low levels of HDL-C and raising the levels may lead to a decrease
of ASCVD. However, clinical trials of high dose niacin, omega-3 fatty
acids or Cholesteryl ester transferase protein (CETP) inhibition did not
improve CV outcomes despite significantly increasing HDL-C.102
The pleiotropic effects of HDL exist independent of HDL-C mass
(measured as HDL cholesterol in lipid profile).102 Thus, HDL-C may
not be the right biomarker to reflect HDL-C function. Until such testing
becomes available to determine functionality of HDL-C, the TRC is in
agreement that the value of HDL-C has yet to be answered by clinical
trial evidence and there is no recommendation to target a particular level
to confer reduction in CV risk.
Future Lipid lowering therapies

Patients with severe hypercholesterolemia with LDL-C levels of >
190 mg/dl, if left untreated, may have markedly increased risk of ASCVD.
Upcoming treatments such as Proprotein convertase subtilisin kexin 9
inhibitors (PCSK9 inhibitors) and mipomersen are promising therapies
that if proven safe, may make treatment goal for cholesterol levels
attainable to these types of patients.103,104 For selected patients with
severe hypercholesterolemia, LDL apheresis may also be considered.
Limitations of the Guidelines

Several limitations were encountered during the process of
creating the 2015 CPG. The evidence obtained from the trials only
involved randomized controlled trials and some meta-analyses. Thus,
we did not consider data from poor quality RCTs ad observational
studies. This approach, however, resulted in a comprehensive set of
evidence based clinical recommendations. The clinical trials analyzed
do not involve Filipino patients, thus analysis and grading of evidence

were downgraded. Because of this, most statements are only
RECOMMENDED. We hope in the future that more clinical trials be
made with Filipino patients as subjects.
The issue on cost were not included in the present guidelines,
compared to the previous one. The presence of generic statin medications
in the Philippines has allowed patients to be prescribed with medications
with less problems on compliance and adherence to treatment.
CONCLUSIONS
Six clinical statements were made by the TRC and the
recommendations revolve around the holistic management of
dyslipidemia. Lifestyle modification should be recommended to
all patients regardless of their CVD risk. High intensity statins are
recommended to lower LDL-C by > 30% or < 70 mg/dl in the primary
and secondary prevention of ASCVD, both for diabetic and non-diabetic
patients. The simplified algorithm was provided to serve as a quick
reference in the management of clinicians.
The updated 2015 CPG is designed to be a guide for clinicians in
managing dyslipidemia for the Filipino patient. This, however, should not
replace sound clinical judgment by doctors and the ultimate decision for
treatment should involve both clinician and the patient.
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Appendix 1. Included Studies
Table 1.1 Characteristics of included studies/substudies on diet

modification
Study/Year Methods Participants Interventions Outcomes
Anderson Randomized 107 moderately Reduced fat Total mortality,
1990 controlled trial hypercholesterolaemic, diet vs usual cardiovascular
non-obese Caucasian diet  mortality, total
men and women aged and non-fatal
30-50 MI, stroke, total,
LDL and HDL
cholesterol
Azadbakht Randomized 100 overweight and Reduced fat Weight,
2007 controlled trial obese people diet vs modified metabolic risk,
fat diet total mortality,
CV mortality.
total MI,
stroke, cancer
diagnoses,
cancer deaths
Ball 1965 Randomized 252 men who have Reduced fat Reinfarction,
controlled trial recently recovered from intake vs. death, MACE,
their first MI dietary advice  CV deaths,
non-fatal MI,
total MI
BDIT Pilot Randomized 295 women with Reduced fat Dietary
Studies 1996 controlled trial mammographic intake vs usual fat, serum
dysplasia diet cholesterol,
total mortality,
weight, BMI,
total and HDL
cholesterol
beFIT 1997 Randomized 409 women and Reduced and Lipids, total
controlled trial men with mild modified fat vs mortalit
hypercholesterolemia usual diet 
Black 1994 Randomized 133 people with non- Reduced fat Incidence of
controlled trial melanoma skin cancer intake vs usual actinic keratosis
diet and non-
melanoma skin
cancer, total
mortality, CV
mortality

Boyd 1988 Randomized 21 women with severe Reduced fat vs Mastopathy
controlled trial cyclical mastopathy for usual diet symptoms,
at least 5 years plasma
hormone and
lipids, total
mortality, CV
deaths
BRIDGES Randomized 106 women diagnosed Reduced fat vs Diet and BMI ,
2001 controlled trial with stage I or II breast usual diet total mortality,
cancer over the past 2 CV deaths, total
years and non-fatal
MI, stroke,
cancer deaths
CARMEN Randomized 290 healthy overweight Reduced fat vs Weight, body
2000 controlled trial people, BMI 26-34 usual diet composition,
lipids , total
mortality, CV
mortality,
cancer deaths
and diagnoses
CARMEN MS Randomized 23 people with at Reduced fat vs Weight, body
sub-study controlled trial least 3 risk factors for usual diet composition,
2002 metabolic syndrome lipids,   total
mortality, CV
mortality,
cancer deaths
and diagnoses,
non-fatal MI,
stroke, heart
failure, PVD
Curzio 1989 Randomized 135 hypertensives with Unclear Blood pressure,
controlled trial cholesterol >6.5mmol/L weight, lipids ,
total mortality,
CV mortality,
cancer deaths
DART 1989 Randomized 2033 men recovering Reduced and Mortality,
controlled trial from an MI modified fat vs reinfarction,
usual diet CV mortality,
MACE, cancer
deaths, total MI,
non-fatal MI
DO IT 2006 Randomized 249 patients with Reduced fat vs CVD, total
controlled trial hyperlipidaemia and usual diet mortality
high risk of CVD

Due Low fat Randomized 73 young overweight Reduced fat vs CVD risk,
2008 controlled trial adults who had lost at usual diet diabetes risk,
least 8% of body weight weight, total
mortality, CV
mortality, total
MI, stroke,
cancer deaths
and diagnoses,
total and non-
fatal MI
Due Low vs Randomized 100 young overweight Reduced CVD risk,
Mod 2008 controlled trial adults who had lost at fat intake vs diabetes risk,
least 8% of body weight modified fat weight, total
mortality, CV
mortality, total
MI, stroke,
cancer deaths
and diagnoses,
total and non-
fatal MI
Due Mod fat Randomized 77 young overweight Modified fat vs CVD risk,
2008 controlled trial adults who had lost at usual diet  diabetes risk,
least 8% of body weight weight, total
mortality, CV
mortality, total
MI, stroke,
cancer deaths
and diagnoses,
total and non-
fatal MI
Dullaart 1992 Randomized 38 Type I diabetics Modified fat vs Albuminuria
controlled trial with elevated urinary usual fat and serum
albumin lipoproteins,
total mortality,
CV mortality,
non-fatal MI,
stroke, cancer
deaths
Frenkiel 1986 Randomized 36 people with Modified fat vs Bile acid
controlled trial radiolucent gallstones average diet kinetics, total
taking ursodeoxycholic mortality
acid
Houtsmuller Randomized 102 adults with newly Modified fat vs Progression
1979 controlled trial diagnosed diabetes usual diet  of diabetic
retinopathy,
total MI and
angina

Lean 1997 Randomized 110 healthy women, Reduced fat vs Weight loss,
controlled trial BMI >25 usual diet  CV risk factors,
total mortality,
CV mortality,
total and non-
fatal MI, stroke,
cancer deaths
Ley 2004 Randomized 176 people with Reduced fat vs Lipids, glucose,
controlled trial impaired glucose usual diet  blood pressure,
intolerance or high total mortality,
normal blood glucose CV death,
total MI,
stroke, cancer
diagnoses,
cancer deaths
McAuley 2005 Randomized 62 overweight and Reduced fat Weight loss,
controlled trial insulin-resistant women vs Modified fat lipids, total
diet  mortality, CV
mortality,
non-fatal and
total MI, stroke,
cancer deaths
and diagnoses
McKeown- Randomized 201 people after 4-monthly Recurrence
Eyssen 1994 controlled trial adenomatous colorectal counseling to of neoplastic
polypectomy encourage a polyps, total
nutritionally mortality, CV
balanced diet mortality,
vs monthly cancer
counseling on diagnoses,
diet to achieve cancer deaths
fat goals 
MeDiet 2002 Randomized 112 healthy Reduced and Breast cancer,
controlled trial postmenopausal modified fat vs weight, lipids,
women with above usual diet  wellbeing,
median serum total mortality,
testosterone CV mortality,
cardiovascular
deaths, non
fatal MI, stroke,
ventricular
fibrillation,
ventricular
overload

Minnesota Randomized 4,393 institutionalised Modified fat MI, total
Coron men controlled trial men living in a mental diet vs. usual mortality,
1989 hospital diet  sudden deaths,
CV mortality,
stroke, cancer
deaths, total MI 
Minnesota Randomized 4,664 institutionalised Modified fat MI, total
Coron women controlled trial women living in a diet vs. usual mortality,
1989 mental hospital diet  sudden deaths,
CV mortality,
stroke, cancer
deaths, total MI 
Moy 2001 Randomized 267 middle-aged Reduced fat Dietary intake,
controlled trial siblings of people with intake vs. usual total mortality,
early CHD, with at least diet  CV mortality,
one CVD risk factor cancer
diagnoses (no
events), cancer
deaths, stroke,
total and non-
fatal MI
MRC 1968 Randomized 395 men who have Modified fat vs MI or sudden
controlled trial survived a first MI usual diet  death, total
mortality, CV
mortality, total
and non-fatal
MI 
MSFAT 1997 Randomized 240 healthy people Reduced fat vs Weight, vitamin
controlled trial aged 20-55 usual diet and fatty
acid intake,
anti-oxidative
capacity, total
mortality, CV
mortality,
stroke, MI,
cancer
diagnoses and
deaths
NDHS Randomized 224 men living in a Modified fat vs Lipid levels
Faribault 1968 controlled trial mental health institute usual diet  and dietary
assessment,
total mortality

NDHS Open Randomized 436 men Reduced and Lipid levels
1st L&M 1968 controlled trial modified fat and dietary
diet vs. usual assessment,
diet total mortality,
CV mortality,
total or non-fatal
MI, peripheral
vascular events
NDHS Open Randomized 782 men Modified fat Lipid levels
1st mod 1968 controlled trial diet vs. usual and dietary
diet assessment ,
CV mortality,
cancer
diagnoses, total
and non-fatal
MI 
NDHS Open Randomized 489 men Reduced and Lipid levels
2nd L&M 1968 controlled trial modified fat vs and dietary
usual diet  assessment ,
CV mortality,
cancer
diagnoses, total
and non-fatal
MI 
NDHS Open Randomized 431 men Modified fat vs Lipid levels
2nd Mod 1968 controlled trial usual diet  and dietary
assessment,
total mortality,
CV mortality,
total or non-fatal
MI, peripheral
vascular events
Nutrition & Randomized 122 pre-menopausal Reduced fat vs Body weight,
Breast Health controlled trial women at increased usual diet dietary
risk of breast cancer compliance ,
total mortality,
CV mortality,
non-fatal
and total MI,
stroke, cancer
diagnoses and
deaths

Ole Study Randomized 30 moderately obese Reduced fat vs Body weight,
2002 controlled trial healthy men usual diet  body fat,
lipids, glucose,
insulin , total
mortality, CV
mortality,
non-fatal
and total MI,
stroke, cancer
diagnoses and
deaths
Oslo Diet- Randomized 412 men with previous Modified fat Coronary
Heart 1966 controlled trial MI diet vs control  heart disease
morbidity and
mortality, total
mortality, non-
fatal and total
MI, stroke 
Oxford Randomized 498 newly diagnosed Reduced Retinopathy,
Retinopathy controlled trial non-insulin dependant and modified total mortality
1978 diabetics dietary fat vs
average diet 
Polyp Randomized 2079 people with at Low fat vs Recurrence
Prevention controlled trial least one adenomatous usual diet of polyps,
1996 polyp of the large bowel prostate cancer,
removed total mortality,
cancer
diagnoses
PREMIER Randomized 537 adults with above Reduced fat vs Blood pressure,
2003 controlled trial optimal BP or stage 1 usual diet  total mortality,
hypertension cardiovascular
mortality,
cancer
deaths, cancer
diagnoses,
diabetes,
stroke, total and
non-fatal MI 
Rivellese 1994 Randomized 63 adults with primary Reduced fat Metabolic
controlled trial hyperlipoproteinaemia vs Modified fat effects, total
diet mortality, CV
mortality,
stroke, total and
non-fatal MI

Rose 1965 Randomized 53 men with angina or Modified fat vs. Cardiac events,
controlled trial following MI usual diet  total mortality,
CV mortality,
cardiovascular
deaths, non-
fatal MI, angina,
stroke
Sacks high Randomized 403 overweight or Reduced fat Weight, total
protein 2009 controlled trial obese adults vs Modified fat mortality, CV
diet mortality,
cancer deaths
and cancer
diagnoses 
Sacks low Randomized 408 overweight or Reduced fat Weight, total
protein 2009 controlled trial obese adults vs Modified fat mortality, CV
diet mortality,
cancer deaths
and cancer
diagnoses 
Sarkkinen Fat Randomized 78 people aged 30- Modified fat vs Lipids and
Mod 1995 controlled trial 60 with serum total usual diet  blood pressure ,
cholesterol levels 6.5- total mortality
8.0 mmol/L
Sarkkinen Red Randomized 78 people aged 30- Reduced and Lipids and
& Mod 1995 controlled trial 60 with serum total modified fat vs blood pressure ,
cholesterol levels usual diet total mortality
6.5-8.0mmol/L
Sarkkinen Red Randomized 78 people aged 30- Reduced fat vs Lipids and
Fat 1995 controlled trial 60 with serum total usual diet blood pressure ,
cholesterol levels total mortality
6.5-8.0mmol/L
Sarkkinen Red Randomized 81 people aged 30- Reduced fat vs Lipids and
vs Mod 1995 controlled trial 60 with serum total modified fat blood pressure ,
cholesterol levels total mortality
6.5-8.0mmol/L
Seppelt 1996 Randomized 70 women with BMI Reduced fat vs Weight, total
controlled trial 24-29 usual diet mortality, CV
mortality, total
and non-fatal
MI, stroke,
cancer deaths
Simon 1997 Randomized 194 women with a high Reduced fat vs Total mortality,
controlled trial risk of breast cancer usual diet  cancer
diagnosis

Sondergaard Randomized 131 people with IHD Reduced and Endothelial
2003 controlled trial plus total cholesterol at modified fat function ,
least 5mmol/L intake vs. usual total mortality,
diet  CV mortality,
cancer
diagnoses and
deaths, stroke,
total MI
STARS 1992 Randomized 60 men with Reduced and Angiography ,
controlled trial angina referred for modified fat total mortality,
angiography diet vs usual CV mortality,
diet  cancer deaths,
stroke, total MI 
Strychar 2009 Randomized 32 people with well Reduced fat Triglycerides
controlled trial controlled type I vs Modified fat and other CVD
diabetes mellitus diet risk factors,
total mortality,
CV mortality,
cancer deaths
and diagnoses
Sydney Diet- Randomized 458 men with previous Modified fat Cardiovascular
Heart 1978 controlled trial MI diet vs usual mortality and
diet  morbidity, total
mortality
THIS DIET Randomized 101 people following a Low fat vs Mortality and
2008 controlled trial first MI modified fat morbidity ,
CV mortality,
cancer deaths,
stroke, total and
non-fatal MI
Veterans Randomized 844 men living at the Modified fat vs. Total mortality,
Admin 1969 controlled trial Veterans Administration usual diet heart disease,
Centre (USA) CV mortality,
cancer deaths,
cancer
diagnoses,
stroke, non-fatal
MI, total MI
WHEL 2007 Randomized 3,112 women with Reduced fat Total mortality,
controlled trial previously treated early intake vs usual invasive breast
breast cancer diet  cancer, CV
mortality

WHI with CVD Randomized 2,277 post-menopausal Reduced fat vs. Breast cancer,
2006 controlled trial women aged 50-79 with usual diet total mortality,
CVD at baseline other cancers,
cardiovascular
events,
diabetes,
CV mortality,
cancer deaths,
cancer
diagnoses,
stroke, non-fatal
MI
WHI without Randomized 58,835 post- Reduced fat vs. Breast cancer,
CVD 2006 controlled trial menopausal women usual diet total mortality,
aged 50-79 with CVD at other cancers,
baseline cardiovascular
events,
diabetes,
CV mortality,
cancer deaths,
cancer
diagnoses,
stroke, non-fatal
MI
WINS 2006 Randomized 2,437 women with Reduced fat Dietary fat
controlled trial localised re-sected intake vs. usual intake, total
breast cancer diet  cholesterol,
weight and
waist, total
mortality,
cancer
diagnoses
Table 1.2. Summary of Clinical Trials for Smoking Cessation

Clinical Trials Methods Participants Intervention Outcomes
Lung Health Randomized 5,887 patients Intensive Total mortality,
Study Program controlled trial smoking COPD, lung
cessation cancer, CV Death
program versus
usual care
MRFIT Randomized 12,866 men In-depth CV mortality,
controlled trial multifactor Fatal and nonfatal
intervention MI, stroke,
program revascularization
aimed at and total mortality
lowering serum
cholesterol, BP
and smoking
cessation
OSLO Study Randomized 1232 high risk diet and Total mortality, CV
controlled trial middle-aged smoking Events, CV deaths
Oslo men cessation
Table 1.3. Summary of Clinical Trials on Exercise

Clinical Trials Methods Participants Intervention Outcomes
LOOK Ahead Randomized 5,145 overweight Intensive lifestyle Death from
controlled or obese intervention that cardiovascular
trial patients with promoted weight causes, nonfatal
type 2 diabetes loss through myocardial
to participate decreased infarction,
caloric intake and nonfatal stroke, or
increased physical hospitalization for
activity angina (composite)
STENO2 Randomized 160 diabetic Stepwise Composite of
controlled patients with implementation of death from
trial microalbuminuria exercise program cardiovascular
causes, nonfatal
myocardial
infarction,
nonfatal stroke,
revascularization,
and amputation.
Chengdu trial Randomized 1232 high risk diet and smoking Total mortality, CV
controlled middle-aged cessation Events, CV deaths
trial Oslo men
Fowler et Randomized 882 men with A “stop smoking Maximum
al/2002 controlled early peripheral and keep walking distance,
trial arterial disease walking” regime myocardial
- a combined infarction, stroke
community-based
intervention of
cessation of
smoking and
increased physical
activity.
Table 1.4. Summary of Clinical Trials in the Use of Statins in Primary Prevention 66
Study/Year Method Participants Intervention Outcomes
WOSCOPS Randomized 6595 men, aged 45-64 years old, fasting LDL Intervention: 40 mg TC - ê 20% Non-fatal MI
1995 controlled Trial cholesterol level of at least 4 mmol/L during the of pravastatin LDL-C ê 26% CHD death
second and third visits, with at least one value Control: placebo HDL-C é 5% Coronary
of ≥4.5 mmol/L and one value of ≤6.0 mmol/L; Follow-up: TG - é 12% revascularization
no serious ECG abnormalities according 5 years Any death
to Minnesota code 1 (pathologic Q waves),
arrhythmia such as atrial fibrillation; and no
history of myocardial infarction or other serious
illness, although men with stable angina who
had not been hospitalized within the previous 12
months
KAPS 1995 Randomized 447 men, LDL-C > 4.25 mmol/L, total cholesterol Intervention: 40 mg TC – 200.8 (22%) IMT of carotid and
controlled Trials < 8.0 mmol/L, body mass index < 32 kg/m2, of pravastatin LDL-C 131.3 (31%) femoral arteries
and liver enzymes (alanine aminotransferase Control: placebo HDL-C 42.5 Myocardial infarction
[ALT] and aspartate aminotransferase [AST]) not Follow-up: 3 years TG – 132.7 Cardiac death
exceeding 1.5-fold the laboratory upper normal Stroke
limit Coronary
revascularization
AFCAPS/ Randomized 6605 participants, men aged 45-73 years old, Intervention: 20-40 After 1 year Fatal and non-fatal MI
TexCAPS 1998 controlled Trials postmenopausal women aged 55-73 years old, mg of lovastatin TC – 184 (17%) Unstable angina
total cholesterol 4-65-6.82 mmol/L, LDL-C 3.36- Control: placebo LDL-C 115 (24%) Sudden cardiac death
4.91 mmol/L, HDL-C ≤ 1.16 mmol/L for men, Follow – up: 5 years TG – 143 Cardiovascular
HDL-C ≤ 1.22 mmol/L for women, triglyceride ≤ HDL-C 39 mortality
4.52 mmol/L, TC/ HDL ratio >6 Coronary heart disease
Intervention: 20-40 mg of lovastatin mortality
Control: placebo Coronary
revascularization
Cardiovascular events
Coronary events
2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines
Study/Year Method Participants Intervention Outcomes
ASCOT-LLT Randomized 10, 305 participants, aged 40-79 years old, with Intervention: 10 mg After 3 years Primary:
2003 controlled Trials either untreated HPN (SBP ≥160 mmHg or DBP of atorvastatin TC – 161.4 (24%) Non-fatal MI and fatal
≥100 mmHg or both), or treated HPN (SBP Control: placebo LDL-C 88 (34%) CHD
≥140 mmHg or DBP ≥90mmHg or both), total HDL-C 50.2
cholesterol of 6.5 mmol/L or lower, not currently Follow-up: 3.5 years TG – 116.8
taking statin or fibrate, at least 3 CV risk factors
(LVH, other specified abnormalities on ECG,
type 2 DM, PAD, previous stroke or TIA, male
sex, 55 years or older, microalbuminuria or
proteinuria, smoking, ratio of TC/ HDL ≥6,
premature family history of CHD
PREVEND IT Randomized 864 participants, aged 28-75 years old, Intervention: 40 mg After 4 years Cardiovascular
2004 controlled Trial persistent microalbuminuria (a urinary albumin of pravastatin TC – 185.3 (17%) mortality
concentration 10 mg/L in 1 early morning spot Control: placebo LDL-C 119.7 (24%) Myocardial infarction
urine sample and a concentration of 15 to 300 and/ or myocardial
mg/24 hours in 2 24-hour urine samples at least Follow-up: 4 years ischemia
once), blood pressure 160/100 mm Hg and no Heart failure
use of antihypertensive medication, and a total Peripheral vascular
cholesterol level 8.0 mmol/L, or 5.0 mmol/L in disease
case of previous myocardial infarction, and no Stroke
use of lipid-lowering medication.
MEGA 2006 Randomized 7832 Japanese men and post-menopausal Intervention: NCEP After 9 years Coronary heart disease
controlled Trial women (3966 control, 3866 intervention), aged step I diet plus 20 TC – 208.9 (14%) Fatal and non-fatal
40-70 years old, total cholesterol concentration mg of pravastatin LDL-C 122.4 (23%) myocardial infarction
5.69-6.98 mmol/L Control: NCEP step HDL-C 62.2 Angina
I diet TG – 107 Stroke
Follow-up: 5 years Sudden cardiac death
Coronary
revascularization
JUPITER 2008 Randomized 17,802 participants, LDL-C <3.4 mmol/L, hsCRP Intervention: 20 mg After 4 years Non-fatal MI
controlled Trial ≥ 2 mg/L, triglyceride <5.6 mmol/L of rosuvastatin LDL-C 55 (49%) Non-fatal stroke
Control: placebo HDL-C 50 Hospitalization for
Follow-up: 1.9 years TG- 99 unstable angina
Coronary
67
revascularization
Cardiovascular
mortality
Table 1.5 Summary of Clinical Trials in the Use of Statins in Secondary Prevention.
68
Study Name Method Intervention Intervention Comparison group (N) Follow-up
group (N) Intervention details
Trials on individuals with ASCVD
4S, 199455 Randomized Controlled Trial 2,221 Medium-intensity Simvastatin 20 mg 2,223 5.4 years
statin
LIPID, 199856 Randomized Controlled Trial 4,512 Low-intensity statin Pravastatin 40 mg 4,502 6.1 years
GISSI, 200057 Randomized Controlled Trial 2,138 Low-intensity statin Pravastatin 20 mg 2,133 Mean 23 months
Amarenco et al, 2006 Randomized Controlled Trial 2,365 High-intensity statin Atorvastatin 80 mg 2,366 Median 4.9 years
(SPARCL)58
Athyros et al, 2002 Randomized Controlled Trial 800 High-intensity statin Atorvastatin 20 mg 800 Mean 3 years
(GREACE)59
Byington et al, 1995 Randomized Controlled Trial 75 Low-intensity statin Pravastatin 40 mg 76 3 years
(PLAC II)60
Koren et al, 2004 Randomized Controlled Trial 1,217 High-intensity statin Atorvastatin 80 mg 1,225 Mean 51.5 months
(ALLIANCE)61
Lemos et al, 2003 Randomized Controlled Trial 844 Medium-intensity Fluvastatin 80 mg 833 3-4 years
(LIPS)62 statin
Meade et al, 1999 Randomized Controlled Trial 10,269 Medium-intensity Simvastatin 40 mg 10,267 5 years
(HPS)63 statin
Pitt et al, 1995 (PLAC Randomized Controlled Trial 206 Low-intensity statin Pravastatin 40 mg 202 3 years
I)64
Rieggeret al, 199965 Randomized Controlled Trial 187 Low-intensity statin Fluvastatin 40 mg 178 1 year
Sacks et al, 1996 Randomized Controlled Trial 2,081 Low-intensity statin Pravastatin 40 mg 2,078 5 years
(CARE)66
Shepherd et al, 2002 Randomized Controlled Trial 2,891 Low-intensity statin Pravastatin 40 mg 2,913 Mean 3.2 years
(PROSPER)67
Shukla et al, 200568 Randomized Controlled Trial 75 Medium-intensity Atorvastatin 10 mg 75 1 years
statin
Sola et al, 200669 Randomized Controlled Trial 54 High-intensity statin Atorvastatin 20 mg 54 1 year
Study Name Method Intervention Intervention Comparison group (N) Follow-up
group (N) Intervention details
Teo et al, 2000 (SCAT)70 Randomized Controlled Trial 230 Low-intensity statin Simvastatin 10 mg 230 3 - 5 years
Yamada et al, 200771 Randomized Controlled Trial 19 Medium-intensity Atorvastatin 10 mg 19 3 years
statin
Yokoi et al, 200572 Randomized Controlled Trial 186 Low-intensity statin Pravastatin 20 mg 187 3 years
Trials on patients with diabetes mellitus
4S, 199773 Randomized Controlled Trial 105 Medium-intensity Simvastatin 20 mg 97 5.4 years
T1/T2, 60 years, MI or statin
AP, Baseline TC 6.7
mmol/L, LDL-C 4.8
mmol/L
ASPEN, 200674 Randomized Controlled Trial 252 Medium-intensity Atorvastatin 10 mg 253 4.0 years
T2, 63 years, MI or statin
IP, Baseline TC 4.9
mmol/L, LDL-C 2.9
mmol/L
CARE, 199875 Randomized Controlled Trial 282 Low-intensity statin Pravastatin 40 mg 304 5.0 years
T1/T2, 61 years,
MI, Baseline TC 5.3
mmol/L, LDL-C 3.6
mmol/L
HPS, 200376 Randomized Controlled Trial 972 Medium-intensity Simvastatin 40 mg 1009 5.0 years
T1/T2 statin
LIPID, 200377 Randomized Controlled Trial 542 Low-intensity statin Pravastatin 40 mg 535 6.0 years
T1/T2, 64 years, MI
or UAP, Baseline TC
5.6 mmol/L, LDL-C 3.7
mmol/L
T1=Type 1 diabetes; T2=Type 2 diabetes; MI=myocardial infarction; AP=angina pectoris; IP=interventional procedure; UAP=unstable angina
69
pectoris.
Table 1.6. Summary of Clinical Trials Using Fibrates in Individuals with Diabetes 70
Study/year Population Baseline lipid values Intervention Duration of Outcome Measures
Mean (SD) mg/dL follow up
INCLUDED
SENDCAP 164 Type 2 diabetes patients, 35 to 65 years old TC 223.3 mg/dL Bezafibrate 400 3 years Change in the carotid
(1998) without history of clinical CV disease LDL 141.3 mg/dL mg OD for 3 intima-media thickness
HDL 39.5 mg/dL years (IMT) measured
Primary prevention study TG 198.5 mg/dL byB-mode ultrasound,
Fatal and Non-fatal MI 0.51 (0.10,2.72) incidence of CHD
DAIS (2001) 418 diabetic patients, 40 to 65 years old with or TC 3301. mg/dL Micronized 3.3 years Mean segment diameter,
without previous coronary intervention LDL 130.5 mg/dL fenofibrate 200 mean
100% DM; 48% with CVD (combined primary & HDL 39.0 mg/dL mg/day for 3 lumen diameter,
secondary prevention) TG 229.5 mg/dL years percentage stenosis
FIELD (2005) 9795 Type 2 diabetes patients, mean age of 62 TC 194 mg/dL Fenofibrate 200 5 years CHD death,
years without history of CV disease LDL 118 mg/dL mg per day non-fatal MI
22% with history of CV disease (combined HDL 42.5 mg/dL
primary & secondary prevention) TG 154 mg/dL
REVIEWED BUT EXCLUDED
BIP (2000) 10% with history of diabetes (N=309) (subgroup TC 213.2 mg/dL Bezafibrate 6.2 years MI (fatal and nonfatal),
analysis), mean age of 60 years LDL 147.5 mg/dL 400 mg/day sudden death
HDL 34.5 mg/dL
Secondary Prevention study TG 156.1 mg/dL
VA-HIT (2002) Men with average age of 64 years, 25% of TC 213.2 mg/dL Gemfibrozil 1,200 5.1 years Combined incidence
subjects with DM (N= 769) with CV disease LDL 147.5 mg/dL mg/day of nonfatal MI &
HDL 34.5 mg/dL death from CAD
Secondary Prevention study TG 156.1 mg/dL
HHS (1987) Men with an average age of 47 years, 3% with a TC mg/dL Gemfibrozil 600 5 years MI (fatal and
history of DM (N=135), without CV disease LDL mg/dL mg/day nonfatal),
HDL mg/dL cardiac death
Primary Prevention study TG mg/dL

Table 1.7 Summary of Clinical Trials in the Use of Fibrates in

Patients in Established ASCVD
Study/Year Population Intervention Outcomes Remarks
Frick/1997 Three hundred slow- Change from the no mortality
(LOCAT) ninety-five men releasegemfibrozil baseline to the
≤70 years old (Lopid SR) follow-up angiogram
post CABG 1200 mg/d or a in the ADS and
with lipid (197 matching placebo. MLD of the tenosis;
intervention vs changes in the
198) primary segments;
all-cause mortality
Rubins/1999 2,531 men with gemfibrozil (1200 Combined
(VA-HIT) coronary heart mg per day) vs incidence of
disease <74 yr placebo nonfatal myocardial
old CHD, with infarction or death
lipid criteria from coronary heart
disease; stroke;
death from any
cause, transient
ischemic attack,
revascularization
procedures, carotid
endarterectomy,
and hospitalization
for unstable angina
or congestive heart
failure.
FIELD/2005 9,795 micronised Primary outcome 2131 with
participants fenofibrate 200 was coronary events previous
aged 50–75 mg daily (n=4895) (coronary heart cardiovascular
years, with or matching disease death or disease and
type 2 diabetes placebo (n=4900) non-fatal myocardial 7664 without
mellitus, and infarction); the
not taking statin outcome for
therapy at study prespecified
entry subgroup
analyses was total
cardiovascular
events (the
composite of
cardiovascular
death, myocardial
infarction, stroke,and
coronary and carotid
revascularisation
72
Table 1.8 Summary of Clinical Trials in the Use of Statins in Patients with ACS
Study Name Intervention: 1: Intervention 1: Number Comparison Number Follow-up
timing details randomised randomized
intervention comparison
group group
De Lemos, 2004 Within 5 days Simvastatin 40 mg for 2265 Placebo for 4 months 2232 2 years
Phase Z of A 1 month then 80 mg then simvastatin 20 mg
to Z
Thompson, Within 24 hours Pravastatin 20-40 mg 1710 Placebo 1698 30 days
2004
PACT
Schwartz, 2004 24-96 hours Atorvastatin 80 mg 1538 Placebo 1548 First 16 weeks
MIRACL
Musashi-AMI Within 96 hours Any Statin 241 No statin 245 Up to 24 months
LAMIL, 1997 Within 48 hours Pravastatin 10-20 mg 36 Placebo 33 3 months
PAIS 2001 Within 48 hours Pravastatin 40 mg 50 Placebo 49 3 months
PTT, 2002 Within 24 hours Pravastatin 40 mg 79 Usual Care 85 4 months
LIPS, 2002 Within 48 hours Fluvastatin 80 mg 844 Placebo 833 45 months
ESTABLISH, Within 24 hours Atorvastatin 20 mg 35 Usual Care 35 6 months
2004
FACS, 2010 Within 24 hours Fluvastatin 80 mg 78 Placebo 78 1 year
Table 1.9. Summary of Clinical Trials using Omega 3 Fatty Acids in Patients with Dyslipidemia
Study/Year Population Intervention Outcomes Remarks
Galan/2011 2501 patients with a Daily dietary supplement containing Major cardiovascular events,
history of myocardial 5-methyltetrahydrofolate (560 μg), vitamin defined as a composite of non-fatal
infarction, unstable B-6 (3 mg), and vitamin B-12 (20 μg) or myocardial infarction, stroke, or
angina, or ischaemic placebo; and containing omega 3 fatty death from cardiovascular disease
stroke acids (600 mg of eicosapentanoic acid
and docosahexaenoic acid at a ratio
of 2:1) or placebo. Median duration of
supplementation was 4.7 years.
GISSI HF/2008 CHF II-IV n-3 PUFA 1 g daily (n=3494) or placebo Cardiovascular mortality, About 30% are on
(n=3481) cardiovascular mortality or admission rosuvastatin
for any reason, sudden cardiac
death, admission for any reason, Cause of HF is
admission for cardio vascular ischemic in 50%
reasons, admission for heart failure,
myocardial infarction, and stroke
GISSI 11 324 patients surviving 1 g daily, n=2,836), vitamin E (300 mg Death, non-fatal myocardial Open label study
PREVENZIONE/1999 recent (<3 months daily, n=2,830), both (n=2830), or none infarction, and stroke
myocardial infarction (control, n=2828) for 3·5 years
SCIMO/1999 223 patients with 112 PUFA vs 111 placebo CAD progression, sudden death, Around <30% are
angiographically proven fatal and nonfatal MI, CHF, on statins

coronary artery disease
PUFA CABG 2005 160 patients for CABG 79 PUFA vs 81 control Occurence of atrial fibrillation and Open label
cardiovascular events CVE, mortality
73
Appendix 2. GRADE Pro Tables
74
Table 2.1 Grade Pro Summary of Evidence on Reduction of Trans/Modified Fat
Bibliography: Cochrane Database Syst Rev. 2012 May 16;5:CD002137
Quality assessment Summary of Findings
Participants Risk of Inconsistency Indirectness Imprecision Publication Overall Study event rates (%) Relative Anticipated absolute
(studies) bias bias quality of effect effects
Follow up evidence (95% CI) (6 months duration)
With Control With Risk Risk
Reduced with difference
dietary fat Control (95% CI)
Major Acute Coronary Event(MACE) (CRITICAL OUTCOME; assessed with: reduction of fat vs control diet)
65508 no no serious Serious no serious Undetected ⊕⊕⊕⊝ 2867/37402 2020/28106 RR 0.86 Study population
(31 studies) serious inconsistency imprecision MODERATE (7.7%) (7.2%) (0.79 to
8 years risk of due to 0.96) 77 per 11 fewer
bias indirectness 1000 per 1000
(3 fewer to
16 fewer)
Moderate
Total mortality (CRITICAL OUTCOME; assessed with: reduction of dietary fat vs control diet)
71790 no no serious Serious1 no serious Undetected ⊕⊕⊕⊝ 2404/40957 1888/30833 RR 0.98 Study population
(21 studies) serious inconsistency imprecision MODERATE1 (5.9%) (6.1%) (0.93 to
(4 fewer to
2 more)
Moderate
Cardiovascular mortality (CRITICAL OUTCOME; assessed with: reduced/modified fat vs usual diet)
(16 studies) serious inconsistency imprecision MODERATE1 (2%) (2.2%) (0.84 to
(3 fewer to
1 more)
Moderate
Fatal and Nonfatal MI (CRITICAL OUTCOME; assessed with: reduction of fat in diet)
8 years risk of due to 1.11) 32 per 3 fewer per 1000
bias indirectness 1000 (from 9 fewer to 4
more)
Moderate
-
Stroke (CRITICAL OUTCOME; assessed with: reduction of dietary fat vs control)
(11 studies) serious inconsistency imprecision MODERATE1 (1.8%) (2%) (0.89 to
8 years risk of due to 1.11) 18 per 0 fewer per 1000
indirectness 1000 (from 2 fewer to 2
bias
more)
Moderate
-
1
No Filipinos included in the study population
75
Table 2.2 GRADE PRO summary of evidence on the benefit of smoking cessation 76

Follow up evidence (95% CI)
With Control With Risk with Risk
Smoking Control difference
cessation with
Smoking
cessation
(95% CI)
Total mortality (CRITICAL OUTCOME)
18023 no no serious serious1 no serious Undetected ⊕⊕⊕⊝ 918/9030 826/8993 RR 0.90 Study population
(from 1
fewer to 18
fewer)
Cardiovascular deaths (CRITICAL OUTCOME)

18023 no no serious serious1 no serious Undetected ⊕⊕⊕⊝ 219/9030 200/8993 RR 0.92 Study population
7 years risk of due to 1.11) 24 per 1000 2 fewer per
bias indirectness 1000
(from 6
fewer to 3
more)
Follow up evidence (95% CI)
With Control With Risk with Risk
Smoking Control difference
cessation with
Smoking
cessation
(95% CI)
CV Events (CRITICAL OUTCOME
18023 no no serious serious1 no serious undetected ⊕⊕⊕⊝ 599/9030 506/8993 RR 0.85 Study population
7 years risk of due to 0.95) 66 per 1000 10 fewer
bias indirectness per 1000
(from 3 to
16 fewer)
1
No Filipinos included in the study.
77
Table 2.3. Grade PRO Summary of Evidence on the Benefit of Exercise 78
Participants Risk of Inconsistency Indirectness Imprecision Publication Overall quality Study event rates (%) Relative Anticipated absolute
(studies) bias bias of evidence effect effects
Follow up (95% CI)
With With Risk with Risk diff with
Control Exercise Control Exercise
(95% CI)
All cause mortality (CRITICAL OUTCOME; assessed with: Moderate exercise vs usual care)
(2 studies) serious inconsistency imprecision MODERATE1,2 (20.7%) (19.7%) (0.86 to
9 years risk of due to 1.05) 207 per 10 fewer per
bias1 indirectness 1000 1000
(from 29 fewer
to 10 more)
CV Mortality (CRITICAL OUTCOME; assessed with: Moderate exercise versus usual care)
5305 serious1 no serious serious2 no serious undetected ⊕⊕⊝⊝ 425/2655 410/2650 RR 0.97 Study population
(2 studies) inconsistency imprecision LOW1,2 (16%) (15.5%) (0.85 to
9 years due to risk 1.09) 160 per 5 fewer per
of bias, 1000 1000
indirectness (from 24 fewer
to 14 more)
Major Acute Coronary Event (CRITICAL OUTCOME; assessed with: Moderate exercise versus usual care)
(2 studies) serious inconsistency imprecision MODERATE1,2 (8.5%) (6.4%) (0.62 to
9 years risk of due to 0.91) 85 per 21 fewer per
bias1 indirectness 1000 1000
(from 8 fewer
to 32 fewer)
Moderate
-
Participants Risk of Inconsistency Indirectness Imprecision Publication Overall quality Study event rates (%) Relative Anticipated absolute
(studies) bias bias of evidence effect effects
Follow up (95% CI)
With With Risk with Risk diff with
Control Exercise Control Exercise
(95% CI)
Non-fatal MI (CRITICAL OUTCOME; assessed with: Moderate exercise versus usual advice)
(1 study) inconsistency imprecision LOW1,2 (21.3%) (6.3%) (0.11 to
due to risk 0.76) 212 per 151 fewer per
of bias, 1000 1000
to 189 fewer)
Stroke (CRITICAL OUTCOME; assessed with: Moderate exercise versus advice)
(2 studies) inconsistency imprecision LOW1,2 (3.8%) (3.3%) (0.67 to
9 years due to risk 1.17) 38 per 5 fewer per
of bias, 1000 1000
to 6 more)
Revascularization (CRITICAL OUTCOME; assessed with: Exercise versus usual care)
5312 serious1 no serious no serious no serious undetected ⊕⊕⊕⊝ 289/2659 284/2653 RR 0.99 Study population
MODERATE1
(2 studies) inconsistency indirectness imprecision (10.9%) (10.7%) (0.84 to

9 months due to risk of 1.15) 109 per 1 fewer per
bias 1000 1000
(from 17 fewer
to 16 more)
79
Table 2.4. GRADE PRO Summary of Evidence on the benefit of statins for primary prevention
80
Quality assessment № of patients Effect
№ of Study Risk of Inconsistency Indirectness Imprecision Other

Relative Absolute Quality Importance
Statins placebo (95%
studies design bias considerations CI) (95% CI)
Total mortality
4 randomised not not serious serious 1 not serious none 544/21237 673/21297 RR 0.81 6 fewer per ⨁⨁⨁◯ CRITICAL
trials serious (2.6%) (3.2%) (0.72 to 1000 (from MODERATE
0.90) 3 fewer to 9
fewer)
3.4% 7 fewer per
1000 (from
3 fewer to
10 fewer)
Cardiovascular death
7 randomised not not serious serious 1 not serious none 240/25198 357/25252 OR 0.67 5 fewer per ⨁⨁⨁◯ CRITICAL
0.79) 3 fewer to 6
fewer)
0.9% 3 fewer per
1000 (from
2 fewer to 4
fewer)
Myocardial infarction
0.70) 7 fewer to
11 fewer)
2.9% 11 fewer
per 1000
(from 9
fewer to 13
fewer)
№ of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance
Statins placebo (95%
studies design bias considerations CI) (95% CI)
Stroke
0.88) 2 fewer to 5
fewer)
1.6% 4 fewer per
1000 (from
2 fewer to 6
fewer)
Cardiovascular events
4 randomised not serious 2 serious 1 not serious none 1028/21239 1411/21305 RR 0.73 18 fewer ⨁⨁◯◯ CRITICAL
trials serious (4.8%) (6.6%) (0.67 to per 1000 LOW
0.79) (from 14
fewer to 22
fewer)
3.6% 10 fewer
per 1000
(from 8
fewer to 12
fewer)
Coronary revascularization
6 randomised not not serious serious 1 not serious none 660/24765 925/24821 RR 0.71 11 fewer ⨁⨁⨁◯ IMPORTANT
trials serious (2.7%) (3.7%) (0.65 to per 1000 MODERATE
0.78) (from 8
fewer to 13
fewer)
2.3% 7 fewer per
1000 (from
81
5 fewer to 8
fewer)
Table 2.5. GRADE PRO Summary of Evidence in the use of Statin in Diabetes without ASCVD. 82

Relative Quality Importance
№ of Study Risk of Other Absolute
Inconsistency Indirectness Imprecision Statins Placebo (95%
studies design bias considerations (95% CI)
CI)
Total Mortality
1 randomised not not serious serious1 not serious none 61/1428 82/1409 RR 0.73 16 fewer ⨁⨁⨁◯ CRITICAL
1.01) (from 1
more to
27 fewer)
Fatal CHD/Cardiovascular death
1.41) (from 5
fewer to 7
more)
Fatal and Non-fatal MI
0.83) (from 6
fewer to
13 fewer)
Relative Quality Importance
№ of Study Risk of Other Absolute
Inconsistency Indirectness Imprecision Statins Placebo (95%
studies design bias considerations (95% CI)
CI)
CVD/Stroke
0.89) (from 2
fewer to 8
fewer)
Acute Major CVD Events (composite)
8 randomised not not serious serious5 not serious strong 597/8083 766/8012 RR 0.78 21 fewer ⨁⨁⨁⨁ CRITICAL
trials serious association (7.4%) (9.6%) (0.7 to per 1000 HIGH (7)
0.86) (from 13
fewer to
29 fewer)
Coronary revascularization (Interventional) Procedures
3 randomised not not serious serious5 not serious none 328/12908 390/12875 RR 0.84 5 fewer ⨁⨁⨁◯ IMPORTANT
0.97) (from 1
fewer to 8
fewer)
RR=relative risk
1. No explanation was provided
2. All the studies are on DM but none were done locally or included Filipinos
3. All the studies except for HPS, were done on DM patients. However, NONE of these studies were done locally or included Filipinos
4. All the studies except for ASCOT were done on DM but none were done locally or included Filipinos
83
5. None of the studies included Filipinos or were done locally

Table 2.6 GRADE PRO Summary table for the Use of Fibrates for the Primary Prevention of Cardiovascular
Events Among Diabetic Individuals. 84

№ of Study Risk of Other Relative Absolute Quality Importance
studies design bias Inconsistency Indirectness Imprecision considerations Fibrates Placebo (95% CI) (95% CI)
Total mortality
3 randomised not not serious serious 1 serious 2 strong 362/5183 333/5194 RR 1.09 6 more ⨁⨁⨁◯ CRITICAL
trials serious association (7.0%) (6.4%) (0.94 to per 1000 MODERATE
1.26) (from 4
fewer to
17 more)
Cardiac Mortality
1.37) (from 4
fewer to
9 more)
Stroke
1 randomised not not serious serious 1 not serious none 158/4895 175/4900 RR 1.1 4 more ⨁⨁⨁◯ CRITICAL
1.4) (from 5
fewer to
14 more)
Major adverse CV events
3 randomised not not serious serious 1 serious 2 none 300/5183 355/5194 RR 0.85 10 fewer ⨁⨁◯◯ CRITICAL
trials serious (5.8%) (6.8%) (0.73 per 1000 LOW
-0.98) (from 1
fewer
to 18
fewer)
MD = mean difference, RR – relative risk
1. None of the trials involved Asians specifically Filipinos

2. DAIS & SENDCAP are small studies
Table 2.7 GRADE PRO Summary of evidence on the use of statins for secondary prevention in individuals with
ASCVD.
№ of Risk of Other Relative Absolute Quality Importance
Study design Inconsistency Indirectness Imprecision statins placebo
studies bias considerations (95% CI) (95% CI)
Total mortality
15 randomized not not serious serious 1 not serious none 2978/30085 3436/30081 RR 0.87 15 fewer ⨁⨁⨁◯ CRITICAL
0.91) (from 10
fewer to
19 fewer)
Fatal coronary heart disease or cardiovascular death
0.84) (from 12
fewer
to 19
fewer) 1
13 randomized not serious 2 serious 1 not serious none 1377/27009 1960/27009 RR 0.70 22 fewer ⨁⨁◯◯ CRITICAL
0.75) (from 18
fewer to
25 fewer)
Stroke
0.84) (from 8
fewer to
14 fewer)
ASCVD=atherosclerotic cardiovascular disease; RR=relative risk.
1
85
Caucasian population; Asians were not well-represented; different socio-economic population (first world vs third world)
2
Heterogeneity I2=57%
Table 2.8 GRADE Pro summary of evidence on the use of high-intensity (atorvastatin 80 or simvastatin 80 mg) vs
medium-intensity (atorvastatin 10 mg or simvastatin 20 mg) statin therapy for secondary prevention in ASCVD 86

high medium Quality Importance
№ of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute
intensity
studies design bias considerations intensity (95% CI) (95% CI)
statin statin
Total mortality
1.04) (from 4
more to 8
fewer)
Cardiovascular mortality
1.03) (from 2
more to 8
fewer)
0.92) (from 6
fewer to
15 fewer)
Stroke
3 randomized not not serious serious 1 not serious none 388/12735 439/12714 ⨁⨁⨁◯ CRITICAL
RR 0.88 4 fewer
1.01) (from 0
fewer to
8 fewer)
ASCVD, atherosclerotic cardiovascular disease; RR=relative risk.
Table 2.9. GRADE PRO Summary table for the Use of Fibrates for the Primary Prevention of Cardiovascular
Events Among Diabetic Individuals.
Fibrates Placebo
studies design bias considerations (95% CI) (95% CI)
Total mortality
1.26) (from 4
fewer to
17 more)
Cardiac Mortality
1.37) (from 4
fewer to 9
more)
Stroke
1 randomised not not serious serious 1 not serious none 158/4895 175/4900 RR 1.1 4 more ⨁⨁⨁◯ CRITICAL
1.4) (from 5
fewer to
14 more)
Major adverse CV events

3 randomised not not serious serious 1 serious 2 none 300/5183 355/5194 RR 0.85 10 fewer ⨁⨁◯◯ CRITICAL
trials serious (5.8%) (6.8%) (0.73 per 1000 LOW
-0.98) (from 1
fewer to
18 fewer)
MD = mean difference, RR = relative risk
87
1. None of the trials involved Asians specifically Filipinos

2. DAIS & SENDCAP are small studies
Table 2.10. Grade PRO Summary of Evidence in the Use of Fibrates as Alternative Treatment to Statin 88
Quality assessment № of patients Effect Quality Importance

Fibrates placebo
All cause mortality
2 randomised not not serious serious 1 not serious none 199/1461 221/1465 RR 0.90 15 fewer ⨁⨁⨁◯ CRITICAL
1.08) (from 12
more to 36
fewer)
8.9% 9 fewer per
1000 (from
7 more to
21 fewer)
CVE
1.15) (from 38
more to 79
fewer)
25.6% 28 fewer
per 1000
(from 38
more to 79
fewer)
Fibrates placebo
Nonfatal MI
0.97) (from 4
fewer to 51
fewer)
14.5% 29 fewer
per 1000
(from 4
fewer to 51
fewer)
Stroke
1.07) (from 4
more to 27
fewer)
6.0% 14 fewer
per 1000
(from 4
more to 27
fewer)
89
90

№ of Study Risk of Other Relative Absolute
Fibrates placebo
studies design bias Inconsistency Indirectness Imprecision considerations (95% CI) (95% CI)
CHD death
1.02) (from 2
more to 36
fewer)
9.3% 20 fewer
per 1000
(from 2
more to 36
fewer)
Revascularization
1 randomised not not serious serious 1 not serious none 266/1264 287/1267 RR 0.93 16 fewer ⨁⨁⨁◯ IMPORTANT
1.08) (from 18
more to 45
fewer)
22.6% 16 fewer
per 1000
(from 18
more to 45
fewer)
1. Serious indirectness in two levels: lack of Filipino population, and intervention not tested in statin-intolerant patients.
Table 2.11. GRADE Pro Summary of Evidence for trials in the use of Statins in Patients with Acute Coronary
Syndrome
studies design bias considerations Statins Placebo (95% CI) (95% CI)
Total Mortality
0.94) (from 3
fewer to
14 fewer)
3.8% 8 fewer
per 1000
(from 2
fewer to
13 fewer)
Cardiovascular death
0.94) (from 2
fewer to
12 fewer)
2.9% 7 fewer
per 1000
(from 2
fewer to
12 fewer)
Non-fatal MI
10 randomised not not serious serious2 serious3 none 344/6872 365/6835 RR 0.93 4 fewer ⨁⨁◯◯ CRITICAL
1.08) (from 4
more to
10 fewer)
4.0% 3 fewer
per 1000
91
(from 3
more to 8
fewer)
Quality assessment № of patients Effect 92
studies design bias considerations Statins Placebo (95% CI) (95% CI)
Stroke
10 randomised not not serious serious4 not serious5 none 54/6872 78/6835 RR 0.70 3 fewer ⨁⨁⨁◯ CRITICAL
0.99) (from 0
fewer to 6
fewer)
1.0% 3 fewer
per 1000
(from 0
fewer to 5
fewer)
Major CV events
10 randomised not serious6 serious4 not serious none 1165/6872 1317/6835 RR 0.88 23 fewer ⨁⨁◯◯ CRITICAL
0.94) (from 12
fewer to
35 fewer)
25.1% 30 fewer
per 1000
(from 15
fewer to
45 fewer)
Revascularization
8 randomised not not serious serious4 serious7 none 582/4925 609/4893 RR 0.95 6 fewer ⨁⨁◯◯ IMPORTANT
1.06) (from 7
more to
17 fewer)
23.0% 12 fewer
per 1000
(from 14
more to
32 fewer)
Table 2.12. GRADEPRO Summary of Evidence in the Use of Omega 3 Fatty Acids as Alternative to Statin
studies design bias considerations Fibrates placebo (95% CI) (95% CI)
All cause mortality
2 randomised not not serious serious 1 not serious none 1250/7697 1368/7674 16 fewer per ⨁⨁◯◯ CRITICAL
RR 0.91
trials serious (16.2%) (17.8%) (0.84 to 1000 (from LOW
0.99) 2 more to 29
fewer)
15.7% 14 fewer per
1000 (from
2 more to 25
fewer)
CV death
RR 0.82
1.08) 12 more to
56 fewer)
14.3% 26 fewer per
1000 (from
11 more to 53
fewer)
Nonfatal MI
RR 0.89
1.13) 4 fewer to 8
fewer)
14.5% 3 fewer per
1000 (from
4 fewer to 8
93
fewer)
94
placebo
studies design bias considerations Fibrates (95% CI) (95% CI)
MACE
1 randomised not not serious serious 1 not serious none 345/4200 405/4188 RR 0.76 13 fewer per ⨁⨁◯◯ CRITICAL
1.07) 16 more to
34 fewer)
6.1% 8 fewer per
1000 (from
4 more to 27
fewer)
Stroke
1 randomised not not serious serious 1 not serious none RR 1.19 ⨁⨁◯◯ CRITICAL
trials serious (0.97, LOW
1.45)
Revascularization
1 randomised not not serious serious 1 not serious none RR 0.97 ⨁⨁◯◯ IMPORTANT
trials serious (0.79, LOW
1.20)
1. Serious indirectness in two levels: lack of Filipino population, and intervention not tested in statin-intolerant patients.
DISCLOSURES
Ms. Duante and Toledo, and Drs. Angus, Baello, Caole-Ang, Gobenchiong, Gloria, Jamorabo-Ruiz, Lazaro,
Merino, Olegario, Ona, Reganit, Santiago-Halasan, Serrano, Te, and Villaseñor-Andaman declared no
potential conflicts of interest. Dr. Pestaño has received non-financial support from industry. Dr. Jimeno is a
consultant or advisory board member of a pharmaceutical company. Drs. Bongosia, Gonzales-Santos and
Guerrero are members of the speakers’ bureau of various pharmaceutical companies. Dr. Sy is a consultant
or advisory board member and has received honorarium from industry. Dr. Acuin is a consultant or advisory
board member and has received honorarium from a non-industry organization. Dr. Cheng is a member of
the speakers’ bureau and has received honorarium from industry. Dr. Llanes is a member of the speakers’
bureau and has received honorarium and other forms of support from industry. Dr. Matawaran is a consultant
or advisory board member, and speakers’ bureau member, from a pharmaceutical company. Dr. Cinco is a
consultant or advisory board member, a speakers’ bureau member, and has received honorarium and other
financial support from industry.

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The physician may use the recommendations

confidently in caring for most patients, and is meant to

The following organizations are represented:

Philippine Society of Hypertension

Manila Doctors Hospital

Philippine Lipid & Atherosclerosis Society

Philippine College of Physicians

Food and Nutrition Research Institute –

Department of Health – Republic of the Philippines

Nutritionists-Dietitians Association of the Philippines

Philippine Medical Association

Las Piñas District Hospital

Philippine Society of Endocrinology, Diabetes and Metabolism

Voting Panelists Nannette R. Rey, MD

Victor L. Lazaro, MD Jorge A. Sison, MD

Romeo U. Merino, MD Alex T. Junia, MD

Frederick Philip B. Gloria, MD Adriel E. Guerrero, MD

Cecilia Cristina Santos-Acuin, MD Lourdes Ella Gonzalez-Santos, MD

Ignacia G. Fajardo, MD Steering committee

Non Voting Panelists Members

2015 Clinical Practice Guidelines for the Management

Adriel E. Guerrero, M.D.

Lourdes Ella Gonzalez-Santos, M.D.

Imelda V. Caole-Ang, M.D.

Felix Eduardo R. Punzalan, M.D.

CQ1 Among patients diagnosed to have dyslipidemia, regardless

CQ2 Among non-diabetics without ASCVD but with multiple risk

CQ3 Among diabetic individuals without ASCVD, should statins

CQ4 Among diabetic individuals without ASCVD, should fibrates

CQ5 Among patients with established ASCVD, should statins be

CQ6 Among individuals with ASCVD, should fibrates be given as

CQ7 Among patients with acute coronary syndrome (ACS),

CQ8 Among patients with established ASCVD or diabetes,

CQ9 Among patients with ASCVD, should omega-fatty acids be

Scope of the guidelines............................................................. 5

Epidemiology of Dyslipidemia in the Philippines.................. 10

Clinical Question 1................................................................... 13

Clinical Question 2................................................................... 22

Clinical Question 3................................................................... 25

Clinical Question 4................................................................... 27

Clinical Question 5................................................................... 27

Statin Treatment Goal................................................................ 30

Clinical Question 6................................................................... 31

Clinical Question 7................................................................... 31

Clinical Question 8................................................................... 33

Clinical Question 9................................................................... 40

Limitations of the guidelines................................................... 47

Appendix 1: Included Studies................................................. 55

Appendix 2: GRADE Pro Tables.............................................. 74

SCOPE OF THE GUIDELINES

findings of microalbuminuria, proteinuria, menopausal status, and left

Statements 1 to 3 of the 2005 CPG. This question still referred to the

Table 1. Clinical Questions

on a 1-to-9 scale following the GRADE categories, where a score of

Table 2. Criteria for recommendation

outcomes. By convention, NNTs are adjusted to the local prevalence

Table 3. Trends of Lipid Profiles of Filipinos Based on NNHeS Data

Bordeline (130-159) to high (≥ 160 43.2% 43.2% 47.2%

HDL-C < 40 mg/dL 54.2% 64.1% 71.3%

of experts representing local stakeholders in the care of dyslipidemia.

EPIDEMIOLOGY OF DYSLIPIDEMIA IN THE PHILIPPINES

The NNHeS is a nationwide survey conducted every 5 years by

Figure 1. Prevalence of high total cholesterol (>240 mg/dL) among