Manajemen Hipertensi

dr. Bagus Andi Pramono, SpJP

Hipertensi
Hipertensi adalah kondisi paling umum
yang didapatkan pada pasien di
primary care.
1 in 3 patients have hypertension
according to NHLBI
Risk factor for MI, CVA, ARF, death

Klasifikasi Hipertensi JNC 7

Category

Systolic
(mmHg)

Diastolic
(mmHg)

Normal

< 120

and

< 80

Pre-HTN

120-139

or

80-89

Stage I

140-159

or

90-99

Stage II

> 160

or

> 100

Hypertension

2013 ESH/ESC Guidelines for the management of arterial hypertension

Denitions and classication of office BP levels (mmHg)*

Hypertension:
SBP >140 mmHg DBP >90 mmHg
Category

Systolic

Diastolic

Optimal

<120

and

<80

Normal

120129

and/or

8084

High normal

130139

and/or

8589

Grade 1 hypertension

140159

and/or

9099

Grade 2 hypertension

160179

and/or

100109

Grade 3 hypertension

180

and/or

110

Isolated systolic hypertension

140

and

<90

* The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic
hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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Diagnosis Hipertensi

Tujuan Pengobatan Hipertensi

Menurunkan Tekanan Darah secara umum
dibawah 140/90 mmHg
Mengontrol Tekanan darah secara stabil
Mengurangi kejadian morbiditas dan
mortalitas Cardio Vaskular
{Mengurangi resiko kerusakan target Organ (Ginjal, Jantung dan Pembuluh
darah)}

Algoritma Tatalaksana HT

JNC 8: Subsequent Management

Reassess treatment monthly
Avoid ACEI/ARB combination
Consider 2-drug initial therapy for
Stage 2 HTN (> 160/100)
Goal BP not reached with 3 drugs, use
drugs from other classes
Consider referral to HTN specialist
LOE: Grade E

2013 ESH/ESC Guidelines for the management of arterial hypertension

Blood pressure goals in hypertensive patients

Recommendations
SBP goal for most
Patients at lowmoderate CV risk
Patients with diabetes
Consider with previous stroke or TIA
Consider with CHD
Consider with diabetic or non-diabetic CKD

<140 mmHg

SBP goal for elderly

Ages <80 years
Initial SBP 160 mmHg

140-150 mmHg

SBP goal for fit elderly

Aged <80 years

<140 mmHg

SBP goal for elderly >80 years with SBP

160 mmHg

140-150 mmHg

DBP goal for most

<90 mmHg

DB goal for patients with diabetes

<85 mmHg

SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease;
DBP, diastolic blood pressure.
The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
Medical Education & Information for all Media, all Disciplines, from all over
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What is the goal BP?

Comparison of Recent
Guideline Statements
JNC 8

ESH/ESC

AHA/ACC

ASH/ISH

>140/90

>140/90 <80 yr
>150/90 >80 yr

>140/90
Threshold
for Drug Rx

>140/90 < 60 yr Eldery SBP >160

>150/90 >60 yr Consider SBP
140-150 if <80 yr

B-blocker
First line Rx

No

Yes

No

No

Initiate Therapy
w/ 2 drugs

>160/100

"Markedly
elevated BP"

>160/100

>160/100

Goal BP
Group

BP Goal (mm Hg)

General
DM*

CKD**

JNC 8:

<60 yr: <140/90

>60 yr: <150/90

< 140/90

< 140/90

ESH/ESC:

< 140/90

< 140/85

< 140/90

Elderly

140-150/90
(<80 yr: SBP<140)

ASH/ISH

< 140/90
>80 yr: <150/90

AHA/ACC

< 140/90

*ADA: < 140/80 or lower

(SBP < 130 if proteinuria)

< 140/90

< 140/90

(Consider < 130/80 if proteinuria)

< 140/90

< 140/90

**KDIGO: <140/90 w/o albuminuria

<130/80 if >30 mg/24hr

2013 ESH/ESC Guidelines for the management of arterial hypertension

Lifestyle changes for hypertensive patients

Recommendations to reduce BP and/or CV risk factors
Salt intake

Restrict 5-6 g/day

Moderate alcohol intake

Limit to 20-30 g/day men,

10-20 g/day women

Increase vegetable, fruit, low-fat dairy intake

BMI goal

25 kg/m2

Waist circumference goal

Men: <102 cm (40 in.)*

Women: <88 cm (34 in.)*

Exercise goals

30 min/day, 5-7 days/week

(moderate, dynamic exercise)
Quit smoking

* Unless contraindicated. BMI, body mass index.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
Medical Education & Information for all Media, all Disciplines, from all over
Powered by
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Class Therapy in Hypertension

1. James PA et al. JAMA 2014;311:50720; 2. Mancia et al. ESH/ESC Guidelines July 2013, Journal of Hypertension : Vol. 31:
Nu.7;1285-1357

16

Role of CCBs
in the 2013 ESH/ESC guidelines

Largely, recommendations for CCBs in the 2013 guidelines1 are

similar to those in the 2007 guidelines2, with one notable
exception
CCBs may be used to initiate either mono- or combination therapy
for hypertension
CCBs can be used in combination with all other antihypertensive drug
classes, with guidelines recommending thiazide diuretics, ARBs and ACE
inhibitors as preferred partners
Dihydropyridine CCBs are the only antihypertensive drug class with least
contraindication limitations

ACE, angiotensin-converting enzyme;

ARB, angiotensin-receptor blocker; CCB, calcium-channel blocker;
ESC, European Society of Cardiology; ESH, European Society of Hypertension
1
Mancia G et al. Eur Heart J 2013; 34: 2159219; 2Mancia G et al. Eur Heart J 2007; 28: 1462536.

Role of CCBs
in the 2013 ESH/ESC guidelines

In the 2013 guidelines1, more detailed guidance is given on the

use of CCBs in patients with specific conditions:

CCBs are preferred in hypertensive patients with LVH and asymptomatic atherosclerosis
CCBs and beta-blockers are preferred, at least for symptomatic reasons, in cases of angina
CCBs and RAS blockers are preferred choices in hypertensive patients with metabolic
syndrome
Some evidence suggests that CCBs are slightly more effective than other antihypertensive
classes in preventing stroke
In several controlled trials, CCBs were more effective than beta-blockers in slowing down
progression of carotid atherosclerosis and in reducing LVH
In a change from the 2007 guidelines2, reassessment of clinical trials involving the
simultaneous use of diuretics, beta-blockers, ACE inhibitors or CCBs did not find CCBs to be
inferior to comparative therapies in preventing heart failure

ACE, angiotensin-converting enzyme;

CCB, calcium-channel blocker; ESC, European Society of Cardiology;
ESH, European Society of Hypertension; LVH, left ventricular hypertrophy; RAS, renin-angiotensin system
1
Mancia G et al. Eur Heart J 2013; 34: 2159219; 2Mancia G et al. Eur Heart J 2007; 28: 1462536.

Golongan Obat Antihipertensi

Diuretik
Inhibitor Adrenergik
Calcium Channel Blocker
Dihidropiridin
Non Dihiropiridin
ACE Inhibitor
Angiotensin II Receptor Blocker (ARB)
Direct Vasodilator

19

CALCIUM CHANNEL BLOCKER

Mekanisme Kerja

Menghambat masuknya ion

kalsium ke dalam sel-sel otot
jantung dan otot polos pembuluh
darah dengan cara memblok kanal
kalsium yang ada di membran sel

21

Efek Mekanisme Kerja

Efek pada pembuluh darah

terjadi vasodilatasi pada arteri sehingga TPR menurun

Efek pada jantung

penurunan denyut jantung

penurunan kekuatan kontraksi jantung

22

Klasifikasi CCB
Klasifikasi CCB

Dihydropyridine
generasi pertama : nifedipine
generasi kedua : amlodipine, felodipine
Non-dihydropyridine
benzothiazepine : diltiazem
diphenylalkilamine : verapamil
diarylaminopropylamine : bepridil

23

Farmakologi
Dihidropiridin

Non-dihidropiridin

vaskuloselektif (hanya bekerja

tidak vaskuloselektif (kontraksi

menghambat di pembuluh darah

perifer dan koroner)

efeknya terhadap konduksi dan

kontraktilitas jantung minimal

vasodilator yang kuat

Menghambat secara selektif
kanal kalsium (90-100%)

jantung dapat menurun)

selain menyebabkan vasodilatasi

pembuluh darah juga dapat
menurunkan konduksi dan
kontraktilitas jantung

Menghambat kanal kalsium (5070%) dan kanal natrium

24

Efek Farmakologi CCB

Efek

Heart Rate
Kontraktilitas
miokard

DHP
(Adalat Oros)

Non DHP
(Diltiazem)

or
or

Konduksi Nodus
Vasodilatasi
perifer

25

Profil Keamanan
CCB tidak memperburuk beberapa kondisi medis tertentu

hipertensi dengan asma

hipertensi dengan diabetes
hipertensi dengan penyakit vaskuler perifer
hipertensi dengan disfungsi ginjal
Tidak menyebabkan batuk

26

Adalat (Nifedipine) OROS:

The Unique CCBs

Adalat OROS/GITS formulation ensures

smooth 24-hour BP control
The OROS/GITS formulation of Adalat
releases nifedipine slowly over a 24-hour
period, allowing maximal BP-lowering effects
with once daily dosing

Dissolution of Adalat OROS/GITS is not

affected by pH, osmolarity, or whether it is
taken with food, ensuring smooth, consistent
release

OROS: Oral Release Osmotic System

AdalatCore Company Data Sheet. Pharmacokinetic properties.

ORal Osmotic Delivery System

(Gastro-Intestinal Therapeutic System)

1. Swanson D.R. et al. (1987) The American Journal of Medicine; 83 (suppl. 6b):3-9.
2. Grundy J.S. et al, (1996) Clin Pharmacokinet; 30(1): 28-51

29

Nifedipine OROS vs Nifedipine

1. Swanson D.R. et al (1987) The American Journal of Medicine;83(suppl 6b) 3-9, 2. Grundy J.S et al. (1996) Clin Pharmacokinet;30(1)
28-51, 3. H. Elliot & P. Meredith. (2004) Journal of hypertension; 22:16411648 , 4. IIMS (1994) ITF;3:2-24

30

Nifedipine GITS/OROS* enables 24-h drug availability

with once-daily dosing unlike older/other formulations
Drug concentration
profiles

Nifedipine IR = Capsule; Nifedipine SR = Retard.

Meredith PA, et al. J Hypertens 2004;22:1641-8.

31

*Nifedipine OROS/ Nifedipine Long-Acting

.. .resulting in smooth onset and a sustained antihypertensive effect over a 24-hour period
BP reduction profile

Nifedipine IR = Capsule; Nifedipine SR = Retard.

Meredith PA, et al. J Hypertens 2004;22:1641-8.

32

*Nifedipine OROS/ Nifedipine Long-Acting

 without cardio-acceleration
Heart Rate
Response
(Placebo corrected)

Nifedipine IR = Capsule; Nifedipine SR = Retard.

Meredith PA, et al. J Hypertens 2004;22:1641-8.

33

*Nifedipine OROS/ Nifedipine Long-Acting

Nifedipine GITS* enables 24-h drug availability with oncedaily dosing unlike older formulations
Drug concentration
profiles

BP reduction
profiles

*Nifedipine OROS/ Nifedipine Long-Acting

Nifedipine IR = Capsule; Nifedipine SR = Retard.
Meredith PA, et al. J Hypertens 2004;22:1641-8.

34

ACTION: nifedipine GITS provides sustained long-term

(>5 years) BP lowering in hypertensive patients

Hypertensive patients (BP 140/90 mmHg; n=3977) and normotensive patients (n=3684).
Nifedipine GITS 30-60 mg once-daily; mean follow-up 4.9 years.
Lubsen J, et al. J Hypertens 2005;23:641-8.

35

ACTION: apart from known vasodilatory AEs nifedipine

GITS has a safety profile comparable to placebo

SAE, serious adverse event.

Patients treated with nifedipine GITS 30-60 mg/day (n=3825) or placebo (n=3840).
Rate=number of patients with event/100 patient-years at risk.
Poole-Wilson PA, et al. Cardiovas Drugs Therapy 2006;20:45-54.

36

Adalat OROS vs Other CCBs

Adalat OROS has more optimal T/P

Ratio in CCB Class

The optimal of T/P ratio shown that the BP fluctuation more

stable/minimal, minimal BP Fluctuation can reduce the risk of organ
damage.
Adalat OROS has more Optimal T/P
Ratio

Nifedipine GITS = Adalat OROS

Compared with amlodipine, Adalat Oros provides

similar BP reduction with less SNS activation

Toal CB, et al. Blood Press 2012:1-8.

INSIGHT: nifedipine GITS provides rapid, effective and

sustained BP lowering with no sympathetic activation

Brown M, et al. Lancet 2000;356:366-72.

40

Efek peningkatan kadar plasma Noradrenalin pada pasien setelah

penggunaan Adalat OROS vs Amlodipine

Plasma Noradrenaline (pg/ml)

500
400

nifedipine GITS

300
200
500

steady state

1st dose

amlodipine

400
300
200

4
5
Time (h)

de Champlain et al 1998

Efek pada Adalat Oros dan Amlodipine dalam Tekanan

Darah dan Heart Rate pada pasien hipertensi.
170

76

150

72
66

nifedipine GITS

110

Heart Rate (bpm)

Blood Pressure (mmHg)

130

70
170

steady state

1st dose

76

150

72

130

66

amlodipine

110

amlodipine

64

90
70

nifedipine GITS

64

90

4 5 6
Time (h)

4 5 6
Time (h)

de Champlain et al 1998

Conclusion
Adalat (Nifedipine) OROS has stable drug release than Nifedipine.
Adalat OROS has Once Daily Dose
Adalat (Nifedipine) OROS has well-established safety and tolerability
profile

Adalat (Nifedipine) OROS has minimal BP Fluctuation than Nifedipine

and other CCB agent, with Optimal T/P ratio (0.81 1.07), better than
other CCBs.

Adalat OROS provides rapid, effective and sustained BP lowering with

no sympathetic activation

Thank you for your attention!

bagus.yogyes@gmail.com

Case
A 58 year old African-American woman
with diabetes and dyslipidemia has a
BP of 158/94 confirmed on several
office visits. Other than obesity, the
exam is normal. Labs show normal
renal function, well-controlled lipids on
atorvastatin and well-controlled
diabetes on metformin. Urine microalbumin is mildly elevated.

Case Question 1
What goal BP is most appropriate for
this patient?
1.
2.
3.
4.
5.

<150/90 mmHg
<130/80 mmHg
<140/90 mmHg
<140/80 mmHg
<140/85 mmHg

Case Question 2
What is the drug of choice to start?
1.
2.
3.
4.
5.
6.

HCTZ
Norvasc
Lisinopril
Losartan
Bystolic
Combination therapy