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MANAGEMENT OF HYPERTENSION

Focus on CCB & JNC VIII

dr. ANDI SULISTYO HARIBOWO, SpPD

INTERNIST

CURRICULUM VITAENama : dr. Andi Sulistyo Haribowo, SpPD

TTL : Malang, 28 Mei 1978

Alamat : Jl. Ters. Sigura-gura C-15 Malang

Phone : 08123591692

Pendidikan Tinggi:

- Sarjana Kedokteran, FKUB Malang, 1999

- Dokter Umum, FKUB Malang, 2002

- Dokter Spesialis Penyakit Dalam, FKUB/Pengurus BesarPerhimpunan Dokter Spesialis Penyakit Dalam Indonesia (PB PAPDI), 2010

Pengalaman kerja:

- Dokter Klinik 24 jam di Pasuruan dan Sidoarjo (2002-2003)

- Dokter Kontrak RSU Ngudi Waluyo, Wlingi, Blitar (2002-2003)

- Dokter PTT Depkes RI Brigade Siaga Bencana (2003-2004)

- Dokter PNS Kota Malang (2004-sekarang) RSUD Kota Malang

- Program Studi Pendidikan Dokter Spesialis Penyakit Dalam(PPDS) RSSA (2006-2010)

- Dokter SpPD di RSU Mitra Delima dan RSU Prasetya Husada KabMalang (2010-sekarang)

- Dosen Luar Biasa FK Universitas Islam Malang (2010-sekarang)

Measurement blood pressure

Persons seated quietly for at least 5 minutes in a chair , with feet on the floor, and arm supported at heart level.

Caffeine, exercise, and smoking should be avoided for at least 30 minutes prior to measurement.

An appropriately sized cuff (cuff bladder encircling at least 80 percent of the arm) should be used to ensure accuracy.

At least two measurements should be made and the average recorded.

For manual determinations,palpated radial pulse obliteration pressure

should be used to estimate SBP—the cuff should then be inflated 20–30 mmHg above this level

The cuff deflation rate for auscultatory readings should be 2 mmHg per second.

SBP is the point at which the first of two or more Korotkoff sounds is heard (onset of phase 1), and the disappearance of Korotkoff sound (onset of phase 5) is used to define DBP.

30/9/2549 CVD S&S Med 4

Blood pressure measurement

30/9/2549 CVD S&S Med 4

Korotkoff sound in BP measurement

Persistent elevation of arterial blood pressure (BP)

~72 million Americans (31%) have BP > 140/90 mmHg

RISKESDAS 2013 25,8% in Indonesia

Most patients asymptomatic

Increasing prevalence with aging of population and epidemic of overweight/obesity

28

3842

47 49 49

55

38

0

20

40

60

Italy Sweden England Spain Finland Germany

Adults aged 35–64 years (data are age- and sex-adjusted), except* (adults aged ≥ 30 years)

Hypertension defined as BP 140/90 mmHg or on treatment

Wolf-Maier et al. JAMA. 2003;289:23632369; Sekikawa, Hayakawa. J Hum Hypertens. 2004; 2004;18:911–912.

Pre

vale

nce o

f hypert

ensio

n (

%)

US Japan*

PREVALENSI HIPERTENSI DI INDONESIA

Source : Data Litbang Depkes 2008

H. + Komplikasi

H. + Keluhan +

Pengobatan tak baik

H. + Keluhan +

Pengobatan baik

H. Tanpa keluhan

Normotensi

Border line

FENOMENA GUNUNG ES

1970 - 1975 1975 - 1980 1980 - 1985 1985 - 1990

Aware (%) 51 64 73 84

Treated (%) 36 34 56 73

Control (%) 16 20 34 55

HIPERTENSION, AWARENESS,

TREATMENT, AND CONTROL RATES

Hypertension:

A Risk Factor for Cardiovascular Disease

9.5

3.3 2.45.0

2.03.5

2.1

45.5

21.3

12.4

6.2

9.97.3

13.9

6.3

22.7

0

5

10

15

20

25

30

35

40

45

50

Man Woman Man Woman Man Woman Man Woman

Normotensive

Hypertensive

Ratio

Risk: 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0

Kannel WB. JAMA 1996;275:1571-1576

Coronary

diseaseStroke

Peripheral artery

disease

Cardiac

failure

Bie

nn

ial a

ge

-ad

jus

ted

ra

te

pe

r 1

,00

0 s

ub

jec

ts

*Individuals aged 40-69 years, starting at blood pressure 115/75 mm Hg.CV, cardiovascular; DBP, diastolic blood pressure; SBP, systolic blood pressure.Chobanian AV et al. JAMA. 2003;289(19):2560-2572.Lewington S et al. Lancet. 2002;360(9349):1903-1913.

Kematian akibat Kardiovaskular Meningkat Dua Kali

Lipat tiap Peningkatan

20-mm Hg TDS atau 10-mmHg TDD*

Cardiovascular

mortality

risk

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

2x

4x

8x

Penurunan Tekanan Darah sebesar 2 mm Hg

Menurunkan Resiko Kardiovaskular hingga 10%

Meta-analysis of 61 prospective, observational studies

1 million adults

12.7 million person-years

Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

2 mm Hg

decrease in

mean SBP 10% reduction

in risk of stroke

mortality

7% reduction

in risk of CHD

mortality

JNC 7 blood pressure classification

in adults aged ≥18 years

BP

Classification

SBP

(mm HG)

DBP

(mm HG)

Normal <120 and <80

Prehypertension 120-139 or 80-89

Stage 1

hypertension140-159 or 90-99

Stage 2

hypertension160 or 100

National Heart, Lung, and Blood Institute. JNC 7 Express. The Seventh Report of the Joint National Committee on

the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2003.

Lifestyle Modification

Modification Approximate SBP reduction

(range)

Weight reduction 5–20 mmHg/10 kg weight loss

Adopt eating plan 8–14 mmHg

sodium reduction 2–8 mmHg

Physical activity 4–9 mmHg

Moderation of

alcohol consumption

2–4 mmHg

Multiple antihypertensive agents

are needed to achieve target BP

AASK MAP <92

Target BP (mmHg)

Number of antihypertensive agents

1

UKPDS DBP <85

ABCD DBP <75

MDRD MAP <92

HOT DBP <80

Trial 2 3 4

DBP, diastolic blood pressure; MAP, mean arterial pressure;

SBP, systolic blood pressure

IDNT SBP <135/DBP <85

ALLHAT SBP <140/DBP <90

1) Bakris GL, et al. Am J Kidney Dis 2000;36:646-661; 2) Lewis EJ, et al. N Engl J Med 2001;345:851-860;

3) Cushman WC, et al. J Clin Hypertens 2002;4:393-404

Combining drugs is better than high

dose monotherapy in BP control

Wald et al. Am J Med 2009;122:290–300

Conclusions from a meta-analysis comparing combination antihypertensive therapy with monotherapy in

over 11,000 patients from 42 trials

‘The extra BP reduction from combining drugs from 2 different classes is

approximately 5 times greater than doubling the dose of 1 drug’

?

2013 ESH-ESC Guideline for Arterial

Hypertension: Choice of Antihypertensive Drugs

Mancia et al. ESH/ESC Guidelines July 2013, Journal of Hypertension : Vol. 31: Nu.7;1285-1357

James PA et al. JAMA 2014;311:507–20;

JNC 8:

Hypertension Management Algorithm

Target BP Recommendation

CKD: chronic kidney disease

1. James PA et al. JAMA 2014;311:507–20; 2. Weber M et al. J Hypertens 2014;32:3–15; 3. Go AS et al. Hypertension

2013;[in press]; 4. Wright Jr JT et al. Annals Intern Med 2014;[in press]

≥80 years:

<150/90 mmHg

≥60 years*:

<150/90 mmHg

Not specified

<60 years:

<140/90 mmHg

<140/90 mmHg

<140/90 mmHg

Not specified

Not specified

<130/80 mmHg

<140/90 mmHg

Not specified but

suggests a lower

target may be

appropriate

with albuminuria

<130/80 mmHg

<140/90 mmHg

Not specified

Not specified but

suggests a lower

target may be

appropriate

General population Elderly populationYoung population (<50 years) CKD Diabetes

<50 yrs

JN

C 8

1A

SH

/IS

H2

AH

A/

AC

C/C

DC

3

*Disputed recommendation4

Treatment Algorithm for Adults with Systolic-Diastolic

Hypertension without another compelling indication

TARGET <140/90 mmHg

Beta-blocker

Long-actingDHP-CCBARBThiazide ACE-I

INITIAL TREATMENT AND MONOTHERAPY

Alpha-blocker

as initial

monotherapy

Lifestyle modification

therapy

2003 Canadian Hypertension Education Program Recommendations.

1950

1960

1970

1980

Diuretics

Beta blockers

CCBs

1-blockers

ACE-inhibitors 1990

2010AT1-antagonists

DRI

Reserpin (1949)

HCT (1958)

Verapamil (1963)

Furosemide (1964)

Propanolol (1965)

Nifedipin (1975)

Prazosin (1977)

Captopril (1981)

Losartan (1995)

Development of Antihypertensive Drugs

Aliskiren (2005)

INDICATIONS FOR INDIVIDUAL DRUG CLASSES

••Strokeprevention

••Chronickidney disease

•••••Diabetes

••••High coronarydisease risk

••Post-MI

••••Heart failure

CCBARBACE inhibitor

-blockerDiureticCompelling

indications

The JNC VII Report. JAMA 2003;289:2560-2572

INDICATIONS FOR INDIVIDUAL DRUG CLASSES

••Strokeprevention

••Chronickidney disease

•••••Diabetes

••••High coronarydisease risk

••Post-MI

••••Heart failure

CCBARBACE inhibitor

-blockerDiureticCompelling

indications

The JNC VII Report. JAMA 2003;289:2560-2572

Dihydropyridine :

1. Nifedipin

2. Amlodipin

Non Dihydropyridine :

1. Diltiazem

2. Verapamil

CCB HR AV & SA node

Myocardial Contractility

Peripheral Contractility

CO CBF

Nifedipine - -

Amlodipin - -

Diltiazem V

Verapamil V

Dosis : 10-40mg

Onset of action : < 20 menit/ SL 3 menit

Metabolism : First pass metabolism in liver

No active metabolit

Excretion : 20 -40% fecal

50-80% renal

Acute neurohormonal effects on blood

pressure homeostasis

Heart rate and cardiac output

Perfusion

Sodium and water retention

Blood pressure

RAA SNS

Mengapa Harus Adalat® OROS?

Dihydropiridine (DHP) CCBs

DHP CCBs : nifedipine & amlodipine

Nifedipine is widely used to treat angina and

hypertension.

Short-acting formulations of nifedipine possibly

harmful. Thus..

Long-acting Nifedipine : GITS / OROS

BHS, Drug Classes, CCBs, Dec 2008

Nifedipine Retard (20 mg)

Nifedipine GITS (60 mg)

Nifedipine Capsule (20 mg)

200

150

100

50

0

Pla

sm

a c

onc

(ng/m

L)

Effect of Nifedipine Formulation on Concentration –Time Profiles: Hypertensive Patients

Meredith & Elliott 2004.

0 4 8 12 16 20 24Time (h)

Nifedipine GITS (60 mg)

Nifedipine Retard (20 mg)

Nifedipine Capsule (20 mg)

50

40

30

20

10

0

-10

Heart

Rate

(beats

/m

in)

Effect of Nifedipine Formulation on Heart Rate Responses: Hypertensive Patients

Meredith & Elliott 2004.

0 4 8 12 16 20 24Time (h)

Pla

sm

a N

ora

dre

naline (pg/m

l)

0 1 2 3 94 5 7 86Time (h)

200

300

400

500

200

300

400

500

amlodipine

Nifedipine GITS

Efek peningkatan kadar plasma Noradrenalin pada pasien setelahpenggunaan Adalat OROS vs Amlodipine

de Champlain et al 1998

1st dose steady state

0.3

0.2

0.1

0

-0.1

-0.2

Chnge in Q

OL r

esponsiv

enes improves

worsen

OverallQOL

Mental Health Index Psychological

Well-Being

PsychologicalDistress

Perceived Health

amlodipine nifedipine GITS

* p<0.05 versus amlodipine

**

Change from Baseline in Quality of Life Summary Scales for Patients Taking Nifedipine GITS or Amlodipine

Testa et al 1998

Incidence of Peripheral Edema

Julius, et. al., VALUE trial, Lancet, June 2004Brown, et. al., INSIGHT study, Lancet 2000

28 %32.9 %

0

10

20

30

40

NifedipineGITS

Amlodipine

VALUE Study(vs. Valsartan)

INSIGHT Study(vs. Thiazide)

Perc

enta

ge o

f Patients

w

ith E

dem

a

Most common side effect of CCBs

Greater incidence in DHPs than non-DHPs (due to its greater vascular selectivity)

THANK YOU !!!