Pengobatan Hipertensi Dgn ARB

7/28/2019 Pengobatan Hipertensi Dgn ARB

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PENGOBATAN HIPERTENSIDENGAN ARB

Prof. Dr. WH Sibuea, Sp.PD


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BLOOD PRESSURE (mmHg)

DiastolicSystolicCATEGORY

DEFINITION AND CLASIFICATION OF BLOOD PRESSURE LEVELTHE 7th REPORT OF THE JOINT NATIONAL COMMITTEE

ON PREVENTION, DETECTION, EVALUATION, AND TREATMENT OF HIGH BLOOD PRESSURE

(2003)

Normal 100


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Classification of hypertension

according to aetiologyPrimary (essential) hypertension

Secondary hypertensionRenal hypertension Renoparenchymal hypertension; renovascular hypertension;

post-kidney transplant hypertension

Endocrine hypertension Pheochromocytoma; primary hyperaldosteronism (Conns

syndrome); deoxycorticosterone-producing tumours;

adrenogenital syndrome; Cushing's syndrome; primary

hyperrenism; acromegaly; hyperparathyroidism; endothelin-

producing tumours; hypo- and hyperthyroidism

Pregnancy-specific (Pre-) eclampsia; transient hypertension

hypertension

Cardiovascular hypertension Coarctation of the aorta; hyperkinetic heart syndrome;

aortic valve insufficiency; sclerosis of the aorta; severe

bradycardia; arteriovenous fistulae

Drug-/alimentation-induced Oral contraceptives; high-dose mineralcorticoids or

hypertension glucocorticoids; erythropoietin; cyclosporine; alcohol

licorice

Neurogenic hypertension Sleep apnoea syndrome; neurological disorders

Stimpel. Arterial Hypertension, 1996; Walter de Gruyter Berlin, New York.


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AUTOREGULATION

BLOOD PRESURE = CARDIAC OUTPUT

HYPERTENSION = INCREASED CO

PERIPHERAL RESISTANCE

INCREASED PR

Preload ContractilityFunction

constrictionStructural

hypertrophy

Fluid Volume Venous

Contractility

Renal

sodium

retention

Decreasedfibration

suface

Sympathetic

nervous system

over activity

Renin

angiotensin

excess

Cell

membrane

alteration

Hyper

Insullinemia

Excess

sodium

intakeGenetic

alteration

Stress Obesity

Endothelium

derrived

factors

X

AND / OR

Genetic

alteration


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Risk factors for the development

of hypertension

Hyperlipidaemia

Black race

Geneticpredisposition

Diabetes

mellitus

Lack of

exercise

Alcohol

Distress (?)

Obesity


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Pada pasien normotensif terdapat variasitekanan darah di urnal.

Pada malam hari tekanan darah turun 10 -20%

Tekanan darah dipengaruhi oleh saraf simpatis

dan sistim renin-angiotensin -aldosteron.


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J Clin Endocrinol Metab 1985;60:1210-1215


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Horm Metab Res 1990;22:636-639


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0

2

4

6

8

10

Blood Pressure & Risk of Stroke


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Effect of SBP and DBP on

Age-Adjusted CAD Mortality: MRFIT

CAD Death Rate per 10,000 Person-Years

100+ 90-99 80-89 75-79 70-74


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Target Organ Damage caused by

Hypertension

Jantung

LVH PJK

Angina pektoris Gagal Jantung

Otak

Stroke, TIA

Demensia

Penyakit Ginjal Kronik (CKD)

Penyakit Arteri perifer

Retinopati


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Hypertension & Risk for ESRD

Compared with BP < 120/80 mmHg,

the adjusted relative risksfordeveloping ESRDin subject without baseline renal disease:

Hsu CY, et al. Arch Intern Med. 2005; 165:923-928.

RR CI BP

1,62 95% CI (1,27 - 2,07) 120-129 / 80- 84

1,98 95% CI (1,55 2,52) 130-139 / 85-89

2,59 95% CI (2,07-3,25) 140-159 / 90-99

3,86 95% CI (3,00 4,96) 160-179 / 100-109

3,88 95% CI (2,82- 5,34) 180-209 / 110-119

4,25 95% CI (2,63-6,86) 210 / 120


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Diastolic BP (mm Hg)

76 84 91 98 105

4.0

3.0

2.0

1.0

Stroke

Risk ratio

Diastolic BP (mm Hg)

76 84 91 98 105

4.0

3.0

2.0

1.0

Myocardial Infarction

Risk Ratio

MacMahon S. J Hypertens. 1990;8(suppl):239-244.

Blood Pressure, Stroke, & CAD


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Hypertension and the risk of

further disease

Disease Relative risk(hypertensives versus normotensives)

Coronary artery disease 2- to 3-fold

Stroke 7-fold

Heart failure 2- to 3-fold

Peripheral vascular disease 2- to 3-fold


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Achieved SBPmm Hg

Risk of a major cardiovascular event reduced

by 22% in the HOT Study

0

5

10

15

20

25

30

170 160 150 140 130

% risk reduction

Optimal SBPreduction in theHOT Study


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Achieved DBPmm Hg

Risk of a major cardiovascular event reduced

by 30% in the HOT Study

0

5

10

15

20

25

30

105 100 95 90 85 80

% risk reduction

Optimal DBPreduction in theHOT Study


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Management of Hypertension

Assess the risk

Treat to target

Lifestyle

Combination therapy

Compliance

Important messages


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Reduce CVD and renal morbidity andmortality.

Treat to BP


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History of antihypertensive drugs

Direct

vasodilators

Alpha-

blockers

Peripheral

sympatholytics

Ganglion

blockers

Veratrum

alkaloids

Central 2agonists

Calcium

antagonists-

non-DHPs

Beta-

blockers

Thiazide

diuretics

Calcium

antagonists-

DHPs

ARBs

1940s 1950 1957 1960s 1970s 1980s 1990s 2000

ACE

inhibitors

DHP, dihydropyridine;ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker

Effectiveness and general tolerability


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Treatment Algorithm for Adults with Systolic-Diastolic

Hypertension withoutanother compelling indication

TARGET


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Hypertension

Without

Compelling indication

Stage 1 Hypertension

Syst. 140 159 OR

Diast. 80 90 mmHg

Thiazide type diuretics

for mostMay consider ACE inh,

ARB, CCB, Betablocker

Or Combination

Stage 2 Hypertension

Syst. > 160 mmHg OR

Diast > 100 mmHg

2 Drug Combination

for mostUsualy thiazide type with

ACE inh. orARB or Beta

Blocker or CCB

JNC VII2003

JAMA. 2003;289


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Possible Combination of Difference Classes of Antihypertensive Agents2003 European Society of Hypertension-European Society of Cardiology

Guidelines for management of arterial hypertension

Calcium

antagonists

AT1-receptors

blockers-blockers

-blockers

Diuretics

ACE inhibitorsThe most rational combinations

Classes of antihypertensive

agents proven to be beneficial

in controlled interventional trial


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Anti-hypertensive effects of

ARBs RAA cascade, ACEIs & ARBs

Various ARBs

Valsartan Antihypertensive Long-

Term Use Evaluation (VALUE)


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Classical "circulating" system (RAAS):

Renin-Angiotensin Systems (I)

Angiotensin II

Angiotensin I

Angiotensinogen

Aldosterone

Na+-retentionK+-loss

glomerular zone

ACE

Renin

Blood pressure

Na+

Sympathetic system

Renin

maculadensa

adrenalglands

adapt. from Dominiak & Unger (eds.) in Ang II-AT1-Receptor Antagonists, Steinkopff (1997)


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t-PA = tissue plasminogen activatoCAGE = chymostatin-sensitiveangiotensin generating enzyme

Local "tissue-bound" system (RAS):

Renin-Angiotensin Systems (II)

AT1 AT2

Bradykinin

inactive fragments

B2B1

Angiotensin II

Angiotensin I

Angiotensinogen

ACE

Renin

specific cellular response

ChymasesCathepsin G

CAGE

t-PACathepsin GTonin

specific cellular response

adapt. from Dominiak & Unger (eds.) in Ang II-AT1-Receptor Antagonists, Steinkopff (1997)


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Distribution ofACE:

Renin-Angiotensin Systems (III)

mod. from Dzau V, Arch Intern Med 153 (1993)

R A S

circulating (plasma) local (tissue)

10 % 90 %

Acute and short-term effectscardiovascular/

renal homeostasis

Long-term effectslocal "organ adaptation"

renal-independent activation


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Angiotensin II generating systems/organs:

Local Renin-Angiotensin-Systems

Tissue/Compartment

HeartBrain

KidneyBlood vessels

atherosclerotic plaquesTestisUterus

Nebenniere

Cell systems (e.g.)

MyocytesNeurons

Mesangium,TubuleEndothelium

Macrophages?Smooth muscle?Glomerulosa cells

mod. from Dzau V, Arch Intern Med 153 (1993)


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GFR

Proteinuria

Aldosterone releaseGlomerular sclerosis

Angiotensin II plays a central role

in organ damage

A II AT1

receptor

Atherosclerosis*

Vasoconstriction

Vascular hypertrophy

Endothelial

LV hypertrophy

Fibrosis

Remodeling

Apoptosis

Stroke

DEATH

*preclinical dataLV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate

Hypertension

Heart failure

MI

Renal failure

dysfunction


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Effects of Angiotensin II at AT1 and AT2Receptors

Blocked by ARBs

AT2AT1

- Vasoconstriction

- Aldosterone release

- Oxidative stress

- Vasopressin release

- SNS activation- Inhibits renin release

- Renal Na+ and H2O reabsorption

- Cell growth and proliferation

- Vasodilation

- Antiproliferation

- Apoptosis

- Antidiuresis/antinatriuresis

- Bradykinin production- NO release

Siragy H.Am J Cardiol. 1999;84:3S8S.


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AngiotensinII

Abnormalvasoconstriction

Activate SNS

AldosteroneVasopressin

Collagen

ContractilityPAI-1/

thrombosis

Plateletaggregation

Superoxideproduction

EndothelinVascular smooth

muscle growth

Myocyte growth

Burnier M, Brunner HR. Lancet. 2000;355:637645.

Pathophysiologic Effects of Angiotensin II


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Actions of Angiotensin II via AT1

Receptor Stimulation

Sistemic (endocrine) effects of circulating angiotensin II-vasoconstictive (preferentially coronary, renal, cerebral)

- Steroidogenic (aldosterone)

- Dipsogenic (CNS effect)

- Renin-supressing (negative feedback)

Tissue-specific effects of angiotensin II as local hormone-Tropic/mitogenic (cardiac and vascular myocytes)

-Inotropic/contractile (cardiomyocytes)

-Chronotropic/arrhythmogenic (cardiomyocytes)

-Thrombogenic (plasminogen actifator inhibitor)

-Oxidative (generation of reactive oxygen species)

-Ion transport channels (myocytes, renal cells)

-Neuroexciation (sympathetic nerve terminals)

-Endothelin stimulation (endothelial cells)


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Various ARBs

Losartan = Cozaar (MSD)

Valsartan = Diovan (Novartis)

Candesartan = Blopress (Takeda)

Irbesartan = Aprovel (Sanofi)

Telmisartan = Micardis (Boehringer Ingelheim)

Eprosartan not available in Indonesia

Olmesartan = Olmetec (Pfizer)


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Comparisons of ARB-Based

Regimens With Control Regimens

BP Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.

0.5 1.0 2.0FavoursControl

FavoursARB

Relative Risk

Stroke

CHD

Heartfailure

Major CVevents

CV death

Totalmortality

4

4

3

4

4

4

Relative Risk(95% CI)

0.79 (0.690.90)

0.96 (0.851.09)

0.84 (0.720.97)

0.90 (0.830.96)

0.96 (0.851.08)

0.94 (0.861.02)

396/8412

435/8412

302/5935

1135/8412

491/8412

887/8412

500/8379

450/8379

359/5919

1268/8379

511/8379

943/8379

Diff. in BP(mean,mmHg)

2 / 1

2 / 1

2 / 1

2 / 1

2 / 1

2 / 1

P

0.46

0.43

0.26

0.78

0.34

0.59

Events/ParticipantsTrials


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VALUE

Valsartan Antihypertensive

Long-Term Use Evaluation


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VALUE: Significance

First trial to compare ARB valsartan, themost to calcium channel blocker,

amlodipine

Designed to evaluate effectiveness of a

valsartan-based regimen vs an

amlodipine-based regimen on overallcardiac outcomes

Mann J, Julius S. Blood Press. 1998;7:176183.


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VALUE: Rationale for Endpoints

Strokes seem to be mostly BP dependent,

whereas coronary and other cardiac events

might be related, to excess of angiotensin II

Consequently, composite cardiac events

were designated as primary endpoints and

stroke was classified as a secondaryendpoint


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In hypertensive patients at high cardiovascular

risk, for the same level of blood pressure

control, valsartan will be more effective than

amlodipine in reducing cardiac morbidity and

mortality

VALUE: Primary Hypothesis

Julius S et al. Lancet. June 2004;363:202231.


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VALUE: Primary Endpoint

Composite cardiac morbidity and mortality sudden cardiac death

fatal/nonfatal MI

evidence of recent MI on autopsy

emergency thrombolytic/fibrinolytic treatment and/or

emergency PTCA/CABG to avoid MI

death during/after PTCA/CABG

new or chronic CHF requiring hospital management

heart failure death

Mann J, Julius S. Blood Press. 1998;7:176183.

VALUE S d E d i t d


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VALUE: Secondary Endpoints and

Pre-specified Analyses

Secondary Endpoints:

fatal/non-fatal myocardial infarction

fatal/non-fatal stroke fatal/non-fatal heart failure

Pre-specified Analyses:

all-cause mortality

new-onset diabetes



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VALUE: DesignElective titration to target BP (


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VALUE: Number of Antihypertensive Medications

Taken Before Randomisation

Data on file. Novartis Pharmaceuticals.

Valsartan (n = 7649)Amlodipine (n = 7596)

%ofPatients

3 or MoreMedications

2Medications

1Medication

None0

10

20

30

40

50


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VALUE: Blood Pressure Changes FromBaseline to the End of the Study

Valsartan-Based Therapy

Amlodipine-Based Therapy

SBPDBP

20

15

10

5

0

mmHg



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BeforeRandomisation Study End

Valsartan-BasedRegimen

Amlodipine-BasedRegimen

VALUE: Trends in SBP Control(


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VALUE: Systolic Blood Pressure in Study

Julius S et al. Lancet 2004;363:202231.

Valsartan(N= 7649)

Amlodipine(N = 7596)

135

140

145

150

155

mmHg

Months (or final visit)

Sitting SBP by Time and Treatment Group

Baseline 1 24 482 3 4 6 12 18 30 36 42 54 60 66

0

1.02.0

3.0

4.0

1 24 48

mmH

g

2 3 4 6 12 18 30 36 42 54 60 66


5.0Difference in SBP Between Valsartan and Amlodipine

1.0

4.0(p


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VALUE: Diastolic Blood Pressure in Study

Valsartan

(N= 7649)

Amlodipine

(N = 7596)

mmHg


Sitting DBP by Time and Treatment Group

mm

Hg

Baseline 1 24 482 3 4 6 12 18 30 36 42 54 60 66

75

85

80

90

0

1.02.0

1 24 482 3 4 6 12 18 30 36 42 54 60 66

Months(or final visit)

3.0

Difference in DBP Between Valsartan and Amlodipine

1.0

4.0

5.0

Julius S et al. Lancet 2004;363:202231.

2.1(p


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VALUE:

Primary Endpoint Results


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VALUE: Primary CompositeCardiac Endpoint

14

12

10

8

64

2

0

Time (months)

0 6 12 18 24 30 36 42 48 54 60 66

ProportionofPatients

WithFir

stEvent(%) Valsartan-based regimenAmlodipine-based regimen

HR = 1.03; 95% CI = 0.941.14; P= 0.49


Number at risk

Valsartan

Amlodipine 7596

7649

7469

7459

7424

7407

7267

7250

7117

7085

6772

6732

6955

6906

6576

6536

5959

5911

3725

3765

1474

1474

6391

6349

O d S iff


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VALUE: Outcome and SBP Differences atSpecific Time Periods: Primary Endpoint

Time Interval(months)

Overall study

3648

2436

1224612

03

48end

Favours amlodipine

1.0 2.00.5

PRIMARY ENDPOINTOdds Ratios and 95% CIs

DSBPmmHg

1.4

1.6

1.82.0

3.8

1.7

2.2

36 2.3

Favours valsartan

4.0



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VALUE:

Total Mortality Result


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VALUE: All-cause Death

Number at risk

Valsartan

Amlodipine 7596

7649

7520

7527

7484

7496

7385

7383

7276

7267

7025

6994

7155

7136

6874

6843

6312

6273

3961

3981

1582

1563

6729

6682

Time (months)0 6 12 18 24 30 36 42 48 54 60 66


WithFirstEvent(%)

16

14

12

10

8

6

4

2

0

Valsartan-based regimen

Amlodipine-based regimen

HR = 1.04; 95% CI = 0.94-1.14; P= 0.45



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VALUE:

Secondary Endpoint Results


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VALUE: Fatal and Non-fatal Stroke


Number at risk

Valsartan

Amlodipine 7596

7649

7499

7494

7455

7448

7334

7312

7195

7170

6918

6877

7055

7022

6744

6692

6163

6093

3846

3859

1532

1516

6587

6515

6

5

4

3

2

1

0

Time (months)0 6 12 18 24 30 36 42 48 54 60 66

Proportio

nofPatients

WithFirstEvent(%)



HR = 1.15; 95% CI = 0.981.35; P= 0.08


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VALUE: Outcome and SBP Differencesat Specific Time Periods: Stroke


Odds Ratios and 95% CIs

Favours valsartan Favours amlodipine

1.0 2.00.5


Overall study

3648

2436

1224

612

03

48end

D SBP(mmHg)

1.4

1.6

1.8

2.0

3.8

1.7

2.2

36 2.3

0.25 4.0

STROKE

VALUE: Fatal and Non Fatal


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Time (months)Number at risk

Valsartan

Amlodipine 7596

7649

7497

7499

7458

7458

7332

7319

7205

7177

6905

6853

7065

7016

6727

6680

6141

6078

3840

3864

1532

1520

6562

6504


WithFirstEvent(%)

7

6

5

4

3

2

1

0

VALUE: Fatal and Non-FatalMyocardial Infarction

0 6 12 18 24 30 36 42 48 54 60 66

Valsartan-based regimenAmlodipine-based regimen

HR = 1.19; 95% CI = 1.02-1.38; P= 0.02


VALUE O t d SBP Diff


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VALUE: Outcome and SBP Differencesat Specific Time Periods: Myocardial Infarction



Overall study

48end

1.0 2.00.5

Myocardial InfarctionOdds Ratios and 95% CIs

DSBP(mmHg)

1.4

1.6

1.8

2.0

3.8

1.7

2.2

2.3

4.00.25

3648

2436

1224

612

03

36

Favours amlodipineFavours valsartan

VALUE: Hazard Ratios for Fatal and


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VALUE: Hazard Ratios for Fatal and

Non-fatal Myocardial Infarction



Hazard RatioValsartan/Amlodipine

Fatal and non-fatal

Fatal

Non-fatal

0.5 1 2

Myocardial Infarction

VALUE: Heart Failure


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Number at risk

Valsartan

Amlodipine 7596

7649

7486

7485

7444

7444

7312

7312

7176

7169

6874

6852

7033

7012

6702

6671

6100

6072

3823

3860

1511

1513

6534

6498

VALUE: Heart Failure

Time (months)0 6 12 18 24 30 36 42 48 54 60 66

9

87

6

5

4

3

2

1

0



HR = 0.89; 95% CI = 0.77-1.03; P= 0.12Proportion

ofPatients

WithFirstEvent(%)


Hospitalisation for HF or death from HF


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VALUE: Outcome and SBP Differencesat Specific Time Periods: Heart Failure

Time interval(months)

Overall study

48end

1.0 2.00.5

Heart FailureOdds Ratios and 95% CIs

D SBP(mmHg)

1.4

1.6

1.8

2.0

3.8

1.7

2.2

2.3

0.25 4.0

3648

2436

1224

612

03

36

Favours amlodipineFavours valsartan


Heart Failure: Hospitalisation for HF or death from HF.

VALUE I id f N t Di b t


62/75

VALUE: Incidence of New-onset Diabetes

New-OnsetDiabetes

(%ofpa

tientsin

treatmen

tgroup)


0

2

4

6

8

10

12

14

Valsartan-basedRegimen

(n = 5254)

Amlodipine-basedRegimen

(n = 5168)

13.1%

16.4%

23% Risk ReductionWith Valsartan

16

18

P< 0.0001

CV Events in Treated


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100

90

80

70

60

50

40

30

Probab

ilityof

Event-FreeS

urvival(%)

Time to Event (years)

0 3 6 9 12 15

Hypertensive Diabetic Patients

Verdecchia P et al. Hypertension. 2004;43:963969.

No diabetes

New-onsetdiabetes

Previouslyknowndiabetes

Patients with new or prior diabetes were 3-times more likely to have a CVevent than those without diabetes.


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VALUE: Incidence of Endpoints

*Fatal and non-fatal.


Valsartan (n = 7649)Amlodipine (n = 7596)

%ofPa

tients

MyocardialInfarction*

CardiacMorbidity

CardiacMortality

PrimaryComposite

0

10

20

30

HeartFailure*

Stroke* All-causeDeath

New-onsetDiabetes

P= 0.49

P= 0.90

P= 0.71

P= 0.02 P= 0.12 P= 0.08

P= 0.45

P< 0.0001

VALUE: Hazard Ratios


65/75


Hazard Ratio

Valsartan/Amlodipine

Primary cardiac composite endpoint

cardiac mortality

cardiac morbidity

All myocardial infarction

All congestive heart failure

All stroke

All-cause death

New-onset diabetes

0.5 1 2

VALUE: Hazard Ratiosfor Pre-specified Analyses


i l


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VALUE: Main Results

BP decrease in the amlodipine group

was more pronounced, particularly

early in the trial

Despite BP differences, the primary

composite cardiac endpoint in both

groups was not different


VALUE: Other Results


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VALUE: Other Results

Total mortality was not different

Incidence of stroke was lower in theamlodipine group

Incidence of non-fatal MI was significantly

lower in the amlodipine group

There was a positive trend in favour ofvalsartan for less heart failure

There was a lower rate of new-onset diabetesin the valsartan group



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The observed difference in stroke ratesappears to be strongly related todifferences in achieved BPs

The benefits of valsartan in heart failureprevention emerged later in the study whenBP differences were smaller, indicating thatthere is a potential beneficial effect of

valsartan beyond BP control

VALUE: Interpretations


VALUE: Conclusions


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Prompt blood pressure control inhypertensive patients at highcardiovascular risk is very important

The between-group differences in heartfailure and diabetes suggest that

valsartan may offer benefits beyond BPcontrol

VALUE: Conclusions



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VALUE: Analysis of ResultsBased on Serial Median Matching

Rationale:

Differences in achieved BP levels in VALUE

precluded valid comparisons of drug effects onoutcomes. Therefore, a statistical technique thatadjusts for BP differences was applied post hoc tocreate treatment cohorts with closely similarcharacteristics

Weber MA et al. Lancet. 2004;363:2047

49.

VALUE: Analysis of Results


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Description:

The novel computerised procedure of Serial Median Matchingwas applied at 6 months, following the treatment adjustmentsintended to achieve BP control.

The programme selected the most median patient (by achievedsystolic BP) in the valsartan group; this patient was paired withone from the amlodipine group ( 2 mmHg) and was matchedalso for age, sex and the presence or absence of prior coronarydisease, stroke and diabetes.

The newly created patient pair was moved to a new database,and the procedure repeated serially until all possible patientpairs were matched.


49.

VALUE: Major Study Endpoints in 5006 Patient


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Composite cardiac events

Stroke

Death

Myocardial infarction

Heart failure

0.6 0.8 1.0 1.2 1.4


Pairs (N = 10,012) on Valsartan- or Amlodipine-

Based Therapies Using Serial Median Matching

Hazard Ratio(95% CI)

P

0.90 (0.791.03) 0.111

1.02 (0.811.28) 0.899

0.96 (0.841.10) 0.566

0.97 (0.801.19) 0.791

0.81 (0.660.99)* 0.040

*P< 0.05.

Weber MA et al. Lancet. 2004;363:204749.

VALUE A l i f R lt


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Serial median matching created valsartan-amlodipine patient pairs matched exactly forsystolic BP and demographic and clinical

characteristics excluding the high and lowextremes of achieved BPs.

It allowed us to address the original studyhypothesis, and demonstrated that for the same

achieved BPs, valsartan in an intermediate dosehad effects similar to amlodipine on most CVendpoints, and was more effective in reducingheart failure hospitalisations.

Conclusions:


49.

l f l


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VALUE: Analyses of ResultsBased on BP Control

Blood pressure control, and rapidity of response,are critical for reducing events in high-risk

hypertension

The significant between-group differences in heartfailure and diabetes suggest that valsartan mayoffer benefits beyond BP control

Overall Conclusions:


49.


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