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INTERVENTION
IN MANAGEMENT OF
HYPERTENSION
Yenny Kandarini
INITIATING PHARMACOLOGICAL
MANAGEMENT OF HYPERTENSION
When to start
Combination drugs
WHEN TO START ?!
Is it definite hypertension
What
have to
evaluate
Stage of hypertension
Risk factors /
target organ
damage
BP consistent
Definite
Drug
treatment
should be
initiated
Kaplan,
2014
JNC VII
BP category
Normal
Systol
ic
(mmH
g)
ESHESC, 2013
<120
&
Diastol
BP
Systol
ic
catego
ic
(mmH
ry
(mmH
g)
g)
<80
Hypertension
Stage 1
Hypertension
Stage 2
120
139
or
Diastol
ic
(mmHg
)
Normal
120
129
&
8084
High
normal
130
139
or
8589
or
9099
140
159
Grade 2
(moderate
)
160
179
or
100
109
Prehypertensi
on
8089
140
159
or
>160
or
Grade 1
(mild)
9099
>100
Grade
3
Chobanian
et al. JAMA 2003;289:256072
Journal
(severe)
>1802013,or31:12811357
>110
of Hypertension
Target organ
damage
Heart diseases
Kidney diseases
Stroke
Retinopathy
Peripheral
Arterial Disease
WHEN?
factors,
asymptomatic
organ damage
or disease
High normal
SBP 130139
or DBP 8589
Grade 1 HT
SBP 140159
or DBP 9099
Grade 2 HT
SBP 160179
or DBP 100
109
Grade 3 HT
SBP 180
or DBP 110
No other RF
No BP
intervention
Lifestyle
changes for
several
months
Then add BP
drugs
targeting
<140/90
Lifestyle
changes for
several weeks
Then add BP
drugs
targeting
<140/90
Lifestyle
changes
Immediate BP
drugs
targeting
<140/90
12 RF
Lifestyle
changes
No BP
intervention
Lifestyle
changes for
several weeks
Then add BP
drugs
targeting
<140/90
Lifestyle
changes for
several weeks
Then add BP
drugs
targeting
<140/90
Lifestyle
changes
Immediate BP
drugs
targeting
<140/90
3 RF
Lifestyle
changes
No BP
intervention
Lifestyle
Lifestyle
Lifestyle
changes for
changes
changes
several weeks
BP drugs
Immediate BP
Then add BP
targeting
drugs
drugs
<140/90
targeting
targeting
<140/90
<140/90
2013 ESH/ESC
Guidelines for the management of arterial hypertension
Population
Diabetes
High risk (TOD or CV risk
factors)
Low risk (no TOD or CV risk
factors)
Very elderly
TOD=target organ damage
SBP
130
140
DBP
80
90
160
100
160
NA
*This higher treatment target for the very elderly reflects current evidence and
heightened concerns of precipitating adverse effects, particularly in frail patients.
Decisions regarding initiating and intensifying pharmacotherapy in the very elderly
should be based upon an individualized risk-benefit analysis.
CHEP, 2014
(James
et al,
2014)
H
(Weber
et al,
2014)
DC
(Go et al.,
2014)
C
(Mancia
et al.,
2014)
(Hackam
et al.,
2013)
(Krause
et al.,
2011)
(Flack
et al.,
2010)
Elderly
150/90
(60+ y)
150/90
(80 + y)
140/90
160
systolic
(80 + y)
150/90
(80 + y)
150/90
(80 + y)
Not
specified
General
no risk
factors of
organ
damage
140/90
140/90
140/90
150/90
160/100
140/90
135/85
General,
+ risk
factors of
organ
damage
140/90
140/90
140/90
140/90
140/90
140/90
130/80
Diabetes
140/90
140/90
140/90
130/80 140/90
Kaplan
Clinical Hypertension,
2014
140/90
130/80
CKD
140/90
140/90
140/90
140/90
140/90
140/90
130/80
Which drug
HOW ?!
Single drug /
combination
Present of compelling
indication
Which
Drugs?!
Diuretic
ACE Inhibitor
CCB
Angiotensin Receptor Blocker (ARB)
Beta Blocker
Heart failure
LV dysfunction
Postmyocardial infarction
Diabetic nephropathy
Nondiabetic nephropathy
LV hypertrophy
Carotid atherosclerosis
Proteinuria/microalbuminuria
Atrial fibrillation
Metabolic syndrome
Heart failure
Postmyocardial infarction
Diabetic nephropathy
Proteinuria/microalbuminuria
LV hypertrophy
Atrial fibrillation
Metabolic syndrome
ACE inhibitorinduced cough
-Blockers
Angina pectoris
Postmyocardial infarction
Heart failure
Tachyarrhythmias
Glaucoma
Pregnancy
Calcium Antagonists
(Dihydropyridines)
Thiazide Diuretics
Isolated systolic hypertension (elderly)
Heart failure
Hypertension (blacks)
Diuretics (Antialdosterone)
Heart failure
Postmyocardial infarction
Loop Diuretics
End-stage renal disease
Heart failure
Johnson RJ, Feehally J, Floege J. 2015.
Comprehensive Clinical Nephrology. 5 th edition.
Pharmacologic
Therapy
Thiazide diuretics
-Blockers
Gout
1.Asthma
2.A-V block (grade 2 or
3)
Calcium antagonists
(dihydropyridines)
1.Metabolic syndrome
2.Glucose intolerance
3.Pregnancy
1.Peripheral artery disease
2.Metabolic syndrome
3.Glucose intolerance
4.Athletes, physically active patients
5.COPD
6.Asthma (use cardioselective blocker)
1.Tachyarrhythmias
2.Heart failure
Contraindications
Compelling
Possible
1.Pregnancy
2.Angioneurotic edema
3.Hyperkalemia
4.Bilateral renal artery
stenosis
1.Pregnancy
Angiotensin receptor 2.Hyperkalemia
blockers
3.Bilateral renal artery
stenosis
Diuretics
(antialdosterone)
Direct renin
inhibitors
1.Pregnancy
2.Hyperkalemia
3.Bilateral renal artery
stenosis
Johnson RJ, Feehally J, Floege J. 2015.
Comprehensive Clinical Nephrology. 5 th edition.
Antihypertensive drugs
Class
Mechanisms
Diuretics
Thiazide diuretics
Loop diuretics
Side Effects
Compelling
Indications
for
Comorbiditi
es
Heart failure,
high CAD risk,
diabetes, stroke
Hypokalemia,
hyponatremia,
hypomagnesemia,
hyperuricemia,
photosensitivity, and
metabolic effects
including dyslipidemia
and impaired glucose
tolerance
Inhibiting sodium,
Hypokalemia, but
potassium, and chloride fewer other metabolic
cotransporter in the
side effects
thick ascending limb of
the loop of Henle National Kidney Foundations Primer On Kidney
Renin-Angiotensin
System Blockers
Mechanisms
Side Effects
Compelling
Indications
for
Comorbiditi
es
Dampening arterial
Heart failure,
wave reflections,
post-MI, high
increasing aortic
CAD risk,
distensibility, and
diabetes, CKD,
venodilation
stroke
Angiotensin converting Blocking the conversion Cough, hyperkalemia,
enzyme (ACE) inhibitors of angiotensin I to
elevated creatinine,
angiotensin II
angioedema, and fetal
toxicity
Angiotensin II receptor
Blocking binding of
Similar to ACE
type I blockers (ARB)
angiotensin II to the
inhibitors, except no
type 1 angiotensin
cough
receptor
Direct renin inhibitors
Blocking the conversion
Similar
toFoundations
ARB;
National
Kidney
Primer On Kidney
of angiotensinogen to
diarrhea at high doses Diseases, 2014
angiotensin I
Calcium Channel
Blockers
Dihydropyridine
Diltiazem
Verapamil
Beta Blockers
Nonselective beta
blockers
Selective beta blockers
Combined alpha and
Mechanisms
Side Effects
Compelling
Indications
for
Comorbiditi
es
High CAD risk,
diabetes
Dependent edema,
gingival hyperplasia
Bradycardia
Bradycardia,
constipation
Reduced exercise
tolerance, depression,
and bronchospasm
Heart failure,
post-MI, high
CAD risk,
diabetes, stroke
Aldosterone
Blocker
Spironolactone
Mechanisms
Side Effects
Blocking aldosterone
receptor
Eplerenone
Compelling
Indications
for
Comorbiditi
es
Heart failure,
post-MI
Androgen blocking
effect, including
irregular menses,
gynecomastia, and
impotence
Less potent, but
fewer side effects
related to androgen
blocking
Peripheral edema
Postural
National
Kidney Foundations Primer On Kidney
hypotension
ACE inhibitors
Captopril
Enalapril
Lisinopril
Angiotensin receptor
clockers
Eprosartan
Candesartan
Losartan
Valsartan
Irbesartan
-Blockers
Atenolol
Metoprolol
Calcium
channel
blockers
Alodipine
Diltiazem extended
release
Nitrendipine
Thiazide-type
diuretics
Dose, mg
Say
50
5
10
RCTs Reviewed,
mg
150-200
20
40
400
4
50
40-80
75
25-50
50
600-800
12-32
100
160-320
300
100
100-200
1-2
1
1-2
1
1
1
1-2
2-5
120-180
10
360
1
1
10
20
1-2
10
2
1-2
1
Bendroflumethiazide
Johnson
RJ, Feehally J, Floege J. 2015. Comprehensive
Clinical
Nephrology. 5 th edition. Elseiver
Saunders;
Chlorthalidone
12.5
12.5-25
1
Single drug
or combination ?!
Target BP
(mmHg)
UKPDS1
DBP 85
ABCD2
DBP 75
MDRD3
MAP 92
HOT4
DBP 80
AASK5
MAP 92
IDNT6
SBP 135/DBP 85
ALLHAT7
SBP 140/DBP 90
ESH/ESC
NICE
JSH
Chobanian et al. JAMA. 2003;289:25602572; Mancia et al. Eur Heart J. 2007;28:14621536; http://www.nice.org.uk/
27
download.aspx?o=CG034fullguideline (accessed January 2010); Ogihara et al. Hypertens Res. 2009;32:3107.
Which combination ?!
blockers
Other
antihyperten
sives
Calcium
antagonist
ACE
Preferred combinations
inhibitors
Useful combinations with limitation
Possible but less well tested
Not recommended
ESH/ESC,2013
32
CHEP, 2014
Population
SBP
DBP
Diabetes
<130
<80
All others < 80 y.a.
<140
<90
(including CKD)
Very elderly ( 80
<150*
NA
*This
higher treatment target for the very elderly reflects current
years)
evidence and
heightened concerns of precipitating adverse effects, particularly in frail
patients. Decisions regarding initiating and intensifying
pharmacotherapy in the very elderly should be based upon an
individualized risk-benefit analysis.
CHEP, 2014
GUIDELINE
Peningkatan TD ringan
Risiko KV rendah
/menengah
Pilihan di
antara
Obat tunggal
Penggantian
obat lain
Obat
sebelumnya
pada dosis
penuh
Dosis penuh
monoterapi
Kombinasi 2
obat pada
dosis penuh
Peningkatan TD dgn
jelas
Risiko KV tinggi/sangat
tinggi
Kombinasi 2
obat
Kombinasi
sebelumnya
pada dosis
penuh
Penggantian
menjadi
kombinasi 2
obat berbeda
Menambah
obat ketiga
Kombinasi 3
obat pd dosis
penuh
55 years or
black at any
age
CCB or
thiazide-type
diuretic
Step 2
Step 3
Step 4
http://www.nice.org.uk/download.aspx?o=CG034fullguideline
Accessed June 2006
Diabetes or CKD
present
Age 60 years
Age< 60 years
All ages
Diabetes present
No CKD
All ages
CKD present with or
without diabetes
Nonblac
k
Initiate thiazide-type
diuretic or ACEI or ARB or
CCB, alone or in
combination
Black
Initiate thiazide-type
diuretic or CCB, alone or in
combination
All races
Initiate ACEI or ARB, alone
or in combination with
other drug class
Diabetes or CKD
present
Age 60 years
Age< 60 years
All ages
Diabetes present
No CKD
All ages
CKD present with or
without diabetes
Nonblac
k
Initiate thiazide-type
diuretic or ACEI or ARB or
CCB, alone or in
combination
Black
All races
Initiate thiazide-type
diuretic or CCB, alone or in
combination
At goal BP?
Yes
No
Reinforce medication and lifestyle adherence
For strategies A and B, add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use
medication class not previously selected and avoid combined use of ACEI and ARB).
For strategy C, titrate doses of initial medications maximum
At goal BP?
Yes
No
Reinforce medication and lifestyle adherence
Add and titrate thizide-type diuretic or ACEI or ARB or CCB (use medication class not
previously selected and avoid combined use of ACEI and ARB
At goal BP?
Yes
No
Reinforce medication and lifestyle adherence
Add additional medication class (eg, -blocker, aldosterone antagonist, or others)
And/or refer to physician with expertise in hypertension management
No
At goal BP?
Yes
JNC 8 (cont)
Continue current
treatment and monitoring
SUMMARY
BP in first measurement
BP 140/80
False
Definitive
Compelling
Indication
Combinatio
n Drugs
Target
BP
KASUS
Kasus 1
INA SH ,2014
Normal Tinggi
TDS 130139
Atau TDD 85
89
Risiko
rendah
12 Faktor risiko
Risiko
rendah
3 Faktor risiko
Risiko
rendah
sampai
sedang
Kerusakan organ,
PGK derajat 3
atau DM
Risiko
sedang
sampai
tinggi
PKV Simptomatik,
HT St I
TDS 140159
Atau TDD 90
99
Risiko
Sedang
Risiko
sedang
sampai
tinggi
Risiko tinggi
HT St II
TDS 160179
Atau TDD 100
109
Risiko
Sedang
Risiko
sedang
sampai
tinggi
Risiko tinggi
Risiko tinggi
HT St III
TDS 180
Atau TDD 110
Risiko tinggi
Risiko tinggi
Risiko tinggi
Risiko tinggi
sampai
sangat tinggi
Normal Tinggi
TDS 130139
Atau TDD 8589
HT St I
TDS 140159
Atau TDD 9099
HT St II
TDS 160179
Atau TDD 100109
HT St III
TDS 180
Atau TDD 110
Perubahan gaya
hidup utk beberapa
minggu
Kemudian konsumsi
obat dg target TD
<140/90
Perubahan gaya
hidup
Segera konsumsi obat
dg target TD < 140/90
12 Faktor risiko
Perubahan gaya
hidup
Tidak ada
intervensi TD
Perubahan gaya
hidup utk beberapa
minggu
Kemudian konsumsi
obat dg target TD
<140/90
Perubahan gaya
hidup
Segera konsumsi obat
dg target TD < 140/90
3 Faktor risiko
Perubahan gaya
hidup
Tidak ada
intervensi TD
Perubahan gaya
hidup
Konsumsi obat dg
target TD < 140/90
Perubahan gaya
hidup
Segera konsumsi obat
dg target TD < 140/90
Perubahan gaya
hidup
Tidak ada
intervensi TD
Perubahan gaya
hidup
Konsumsi obat dg
target TD < 140/90
Perubahan gaya
hidup
Segera konsumsi obat
dg target TD < 140/90
PKV Simptomatik,
PGK derajat 4 atau
DM dgn kerusakan
organ/faktor risiko
Perubahan gaya
hidup
Tidak ada
intervensi TD
Perubahan gaya
hidup
Konsumsi obat dg
target TD < 140/90
Perubahan gaya
hidup
Segera konsumsi obat
dg target TD < 140/90
Advice
Advice
Pastikan diagnosis hipertensi
Perubahan gaya hidup untuk
beberapa minggu
Kemudian konsumsi obat
antihipertensi
Target TD <140/90 mmHg
Pilihan obat :
diuretic thiazide/ACE/ARB/CCB/BB
CASE 2
Laki-laki 50 tahun, TD 170/110 mmHg, IMT
27, SC 1.2, GDP 178 mg/dL, 2JPP 238
mg/dL, LVH, Kardiomegali, proteinuria
Ass: Hipertensi stadium II, CKD, DM
risiko tinggi
Penatalaksanaan :
Perubahan gaya hidup
Konsumsi obat antihipertensi
Target < 140/90 mmHg
Peningkatan TD ringan
Risiko KV rendah
/menengah
Pilihan di
antara
Obat tunggal
Penggantian
obat lain
Obat
sebelumnya
pada dosis
penuh
Dosis penuh
monoterapi
Kombinasi 2
obat pada
dosis penuh
Peningkatan TD dgn
jelas
Risiko KV tinggi/sangat
tinggi
Kombinasi 2
obat
Kombinasi
sebelumnya
pada dosis
penuh
Penggantian
menjadi
kombinasi 2
obat berbeda
Menambah
obat ketiga
Kombinasi 3
obat pd dosis
penuh
blockers
Other
antihyperten
sives
Calcium
antagonist
ACE
Preferred combinations
inhibitors
Useful combinations with limitation
Possible but less well tested
Not recommended
ESH/ESC,2013
Thank you