PENATALAKSANAAN DISLIPIDEMIA

DALAM UPAYA
PENCEGAHAN PENYAKIT JANTUNG
KORONER

Triatmo Budiyuwono SpJP(K),FIHA,FAPSIC

Conga 69
Yogyakarta 3 Maret 2017
 HDL inhibit MCP-1
VESSEL
expression
LUMEN Monocyte LDL

Adhesion
molecule MCP-1 LDL
HDL inhibit

Oxidation of LDL
ARTERIAL
INTIMA Cytokines Modified
LDL

Macrophage Foam cell

Barter P.
Eur Heart J 2004; 69(suppl 6):A19-A22 HDL promote cholesterol efflux
 Hubungan Serum Cholesterol dan Mortalitas

Verschuren WM et al. JAMA 1995;274(2):131136

Insidens PJK : Kadar HDL-C dan Kadar TG

200
TGs (mg/dL) <80
* 80-119
*
CHD/1000/10 Years

*
150 >119
*
100

50

0
<50 50-60 >60
* P < 0.05
HDL-C (mg/dL)

Castelli WP. Am J Cardiol. 1992;70:3H-9H.

 30 4S-PI

25 20 Prevention
4S-Rx
20
CV events (%)

15 LIPID-PI
CARE-Rx LIPID-Rx

CARE-PI
10
WOSCOPS-PI
TNT-Rx TNT-PI WOSCOPS-Rx
5 AFCAPS-TexCAPS-Rx
ASCOT-Rx
AFCAPS-TexCAPS-PI 10 Prevention
ASCOT-PI

50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
LDL-C achieved (mg/dl)

Ballantyne CM. Am J Cardiol. 1998;82:3Q12Q.,

Halcox JPJ, Deanfield JE. Circulation. 2004;109[supplII]:II-42II-48., and
LaRossa JC, et al. N Engk J Med 2005;352
 JUPITER - Primary Endpoint
Time to first occurrence of a CV death, non-fatal stroke, non-fatal
MI, unstable angina or arterial revascularization
0.08
Placebo
Hazard Ratio 0.56
(95% CI 0.46-0.69)
Cumulative Incidence

P<0.00001
0.06

Rosuvastatin 20 mg
0.04
0.02

NNT for 2y = 95
5y* = 25
0.00

0 1 2 3 4
Number at Risk Follow-up (years)
Rosuvastatin 8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 157
Placebo 8,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174

*Extrapolated figure based on Altman and Andersen method Ridker P et al. N Eng J Med 2008;359: 2195-2207
 PROVE IT-TIMI 22 (ACS) CARDS (DM)
RRR 37% (95% CI: 17-52)
30 15
Prava -16%

Cumulative hazard (%)

25 P=.001 Placebo
20
Atorva 10
% 15 Atorva
10 5
P=.005
5

0
0
0 3 6 9 12 15 18 21 24 27 30 0 1 2 3 4 4.75
Months Years
Cannon CP, et al N Engl J Med 2004;350:1495-1504 Colhoun HM, et al. Lancet. 2004;364:685-696.

20 PROSPER (Elderly) SPARCLE (Stroke)

Fatal or nonfatal stroke (%)

15 Placebo
% of events

P=.014
10

Prava
5

0
0.5 1 1.5 2 2.5 3 3.5 4
Years
Sheperd J et al. Lancet 2002;360:1623-30 The SPARCLE Investigators N Engl J Med 2006;355:549-59.
 Thicker fibrous cap
More collagen
VULNERABLE
PLAQUE

Thin fibrous cap

Collagen-poor Intima
Media
Adventitia Less macrophages
Less oxLDL

Many macrophages
(MMPs, tissue factor, PAI-1)
Prominent oxLDL
Less stenosis

Aikawa M, Libby P. Cardiovasc Pathol 2004;13:125-38

Rangkuman:

Tingginya kadar LDL-C dan TG serta rendahnya

kadar HDL-C berperan penting pada terbentuknya
aterogenesis dan berhubungan dengan resiko
PJK telah dibuktikan dng studi epidemiologis.
Namun resiko PJK hanya dapat diturunkan
dengan intervensi menurunkan LDL-C
Menurunkan kadar LDL-C baik pada prevensi
primer maupun sekunder terbukti dapat
mencegah kejadian resiko kardiovaskularR
 Faktor Resiko Berdasarkan
NCEP ATP III 2001, 2004 dan
Guideline ESC/EAS 2011
 Kategori Resiko

# 6 Faktor Resiko Mayor

# Penyakit Jantung Koroner (PJK)

# Ekivalen PJK
 Faktor Resiko Mayor
( ESC/EAS 2011 )
Gender
Umur
Tekanan Darah Sistolik
Kadar Total Cholesterol
HDL - C
Merokok
 PJK (sebagai indikator resiko
PJK yg terdokumentasi dng pemeriksaan invasif atau non
invasif (angiografi , pencitraan nuklir , stress
echocardiografi)
Angina Stabil

Angina Tidak Stabil / Sindrom Koroner Akut

Infark Miokard

Iskemia miokard yg secara klinis signifikan

Prosedur / Tindakan (angioplasti atau CABG)
 Resiko yang ekivalen dengan PJK

Penyakit pembuluh darah perifer

Penyakit aterosklerotik
Aneurisma aorta abdominalis
bukan Koroner
TIA/Stroke

Diabetes Mellitus
Gula darah puasa >/= 126 mg/dL
tipe II ( T2DM )

Dengan kerusakan target organ (mis.

Diabetes Mellitus tipe I Mikroalbuminuria)

Peny. Ginjal kronik eGFR < 60 mL/min/1.73 m2

Penilaian Resiko PJK
berdasarkan
SCORE system
 High CVD Low CVD

Bax, Jeroen et al; EHJ; 2011;32:1769-1818

Reiner et al; Management of Dyslipidemia - ESC Pocket Guidelines
 Tingkat Resiko Berdasarkan
Guideline ESC/EAS 2011
Resiko Sangat Tinggi
Diketahui adanya CVD termasuk stroke iskemic dan PAD
T2DM atau T1DM dengan kelainan Organ Target spt microalbuminuria
Gagal Ginjal Kronik dengan eGFR <60ml/min/1.73m2
Kalkulasi resiko dlm 10 thn dengan SCORE 10%.
Resiko Tinggi
Peningkatan menyolok faktor resiko tunggal seperti familial dyslipidaemia,
dan/atau hipertensi berat.
Kalkulasi SCORE 5% - 10% untuk resiko 10-thn kemungkinan CVD (fatal)
Resiko Sedang
Subjects yang dianggap dlm resiko sedang : SCORE :1% - 5% dalam 10 years
Resiko rendah
Individu dengan SCORE 1%.
 Diagnostic Criteria for the Clinical Diagnosis of
Heterozygous Familial Hypercholesterolemia
Criteria 2 Score

Family 1 degree relative known1

st w/ premature CAD and/or
** 1
history 1 degree relative w/ LDL-C >95 centile
st th

st 6
1 degree relative with Xanthelesma and/or children 2
4
<18 with LDL-C >95 centile
th

Clinica Has premature CAD Diagnostic

** 2
l 8
Has premature cerebral/peripheral vascular disease 1
history
5
Phys. Xanthelesma 6
exam Arcus cornealis below the3
age of 45 yrs 4
LDL-C > 330 mg/dL 1 8
250-239 mg/dL 5
190-249 mg/dL 3
155-189 mg/dL 1
Sasaran Kadar LDL dan non-HDL-C
Guideline ESC/EAS 2011
 Rekomendasi ESC/EAS utk
Target (absolut) Kadar LDL-C

Kategori Resiko LDL-C

Resiko Sedang < 115 mg/dL

Resiko Tinggi < 100 mg/dL

Rusinko Sangat Tinggi < 70 mg/dL

Reiner Z, et al. EHJ;2011:32:1769-1818

 Pada pasien dng resiko tinggi atau resiko sedang -
tinggi disarankan dosis terapi harus dapat mencapai
penurunan setidaknya 30% to 40% dari kadar LDL-C
awal terapi.1

Pada resiko sangat tinggi pasien yang tidak dapat

mencapai target, direkomendasikan untuk
setidaknya penurunan 50% dari kadar awal.2
a

1. Grundy SM, et al. J Am Coll Cardiol 2004;44:720-32

2. Reiner Z, et al. Eur Heart J;2011:32:1769-1818
Intervensi Gaya Hidup
 Intervensi Gaya hidup ditujukan utk

Menurunkan LDL-C Meningkatkan HDL-C Menurunkan TG

Menurunkan dietary saturated fat

Meningkatkan dietary fiber

Mengurangi jumlah dietary carbohydrate

Mengurangi konsumsi
alkohol

Meningkatkan aktivitas fisik menjadi habitual

Mengurangi kelebihan Berat Badan

Stop merokok

Reiner Z, et al. EHJ;2011:32:1769-1818

TERAPI
 Strategi Intervensi (ESC) tergantung dari
Score (%) dan Kadar LDL-C

Total CV LDL C (mg/dL)

Risk
(SCORE) <70 70 <100 100 <155 155 <190 190
%
<1 No No LSI LSI LSI, drug if
intervention intervention uncontrolled

1 <5 LSI LSI LSI, drug if LSI, drug if LSI, drug if

uncontrolled uncontrolled uncontrolled

>5 <10, LSI, LSI, LSI + drug LSI + drug LSI + drug
or high risk consider consider therapy therapy therapy
drug if MI drug if MI

10, or LSI, LSI + drug LSI + drug LSI + drug LSI + drug
very high consider therapy therapy therapy therapy
risk drug if MI

LSI = Lifestyle Intervention

MI = Myocardial Infarction

Reiner Z, et al. EHJ;2011:32:1769-1818

 Korea Acute Myocardial Infarction Registry:
Primary Endpoint Events

Lee KH, et al. J Am Coll Cardiol 2011;58:166471

 Follow Up Jangka Panjang
Terapi dng Statin

Ford I, et.al. N Eng J Med 2007; 357:1477 - 86

 Focus on ASCVD Risk Reduction:
4 statin benefit groups /ACC 2013

LDL-C level
Clinical ASCVD 190 mg/dL

Estimated 10-year
risk of ASCVD of
Diabetes, aged
7.5%, 40-75
40-75 years,
years of age, and
with LDL-C
with
70-189 mg/dL
LDL-C 70-189
mg/dL
* Moderate- or high-intensity statin therapy recommended for these 4 groups
Clinical ASCVD defined as acute coronary syndromes, history of MI, stable or unstable angina, coronary or arterial
revascularization, stroke, transient ischemic attacks, or peripheral artery disease
Estimated using Pooled Cohort Risk Assessment Equations

Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at:

http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed November 13, 2013.
 Intensity of Statin Therapy / ACC 2013

High-Intensity Statin Moderate-Intensity Low-Intensity Statin

Therapy Stain Therapy Therapy

LDLC 50% LDLC 30% to <50% LDLC <30%

Atorvastatin (40)80 Atorvastatin 10 (20) mg Simvastatin 10 mg

mg Rosuvastatin (5) 10 mg Pravastatin 1020 mg
Rosuvastatin 20 (40) mg Simvastatin 2040 mg Lovastatin 20 mg
Pravastatin 40 (80) mg Fluvastatin 2040 mg
Lovastatin 40 mg Pitavastatin 1 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg bid
Pitavastatin 24 mg

Lifestyle modification remains a critical component of ASCVD risk reduction, both prior to and in concert with the use
of cholesterol lowering drug therapies.

Statins/doses that were not tested in randomized controlled trials (RCTs) reviewed are listed in italics
Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL
Initiation of or titration to simvastatin 80 mg not recommended by the FDA due to the increased risk of myopathy, including
rhabdomyolysis.
 Perbaikan kadar Lipid Serum dengan Pitavastatin
(Studi respons Dosis pada minggu ke 12)
LDL-C TC HDL-C
(mg/dL) (mg/dL) (mg/dL)
300 350 65
61.8
299.0* (83)
288.2* (84)
250 300 (90) 281.4* 59.0
218.2* (90) 60
204.8* (81)
(79)
(88) 198.7*
56.1
(81)
200 250 (80)
55 55.0*
222.0
(83) (90)
150 200 200.5 200.2
135.7 (80) (81)
(81) 51.1*
116.8 50 (84)
115.1 49.6*
100 (75)
(76)
150
*** *** *** *** *** *** *** (90) *** ***
-34% -42% -47% -23% -29% -33% +7.3 mg/dL+5.9 mg/dL +7.9 mg/dL
0 0 0
1 mg/day 2 mg/day 4 mg/day 1 mg/day 2 mg/day 4 mg/day 1 mg/day 2 mg/day 4 mg/day

* week 0 ( ) :Number of cases

*** : p<0.001 (vs. week 0) by one sample t-test
Subjects: Hypercholesterolemia (including FH)
Dosage: 1mg, 2mg or 4mg, once a day for 12 weeks Saito Y, et al. J. Clini. Ther. Med. 2001; 17: 829
 Dosis tinggi darihigh-potency statin
plus ezetimibe diperlukan utk mencapai
target LDL-C terrendah pada pasien
dengan resiko tinggi dan sangat tinggi
dimana diharapkan terjadi penurunan
60% LDL-C dari baseline
 LDL-C Reduction With Each Titration of Rosuvastatin,
Atorvastatin, Simvastatin, or Pravastatin

Rosuvastatin (mg) Atorvastatin (mg) Simvastatin (mg) Pravastatin (mg)

Rosuvastatin mg Atorvastatin mg Simvastatin mg Pravastatin mg

Mean %
Mean %
Change
From
In LDL-C
from
Untreated
Baseline

p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; p<0.002 vs atorvastatin 20, 40 mg;
simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg; p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80
Jones
mg; pravastatin PH et al. Am J Cardiol. 2003;92:152160
40 mg
KESIMPULAN
Intervensi Gaya Hidup tetap
merupakan modalitas utama pada
manajemen klinis

Kadar LDL-C adalah target utama

terapi, usaha menurunkan hingga
mencapai target berdasarkan kategori
resiko

Target LDL-C mutlak harus tercapai

sebelum mempertimbangkan target
minimal.