3 Hipertensi

Bag-Bag-SMF KardiologiSMF Kardiologi & Kedokteran Vaskular & Kedokteran Vaskular

FK Universitas Cendrawasih

HipertensiHipertensi

Franklin, S.S., J Hypertens 1999; 17 (suppl 5): S29-S36

0

10

20

30

40

50

60

70

18-29 30-39 40-49 50-59 60-69 70-79 80+

SBP > 140 mm Hg DBP > 90 mm Hg

age (yrs)

pre

vale

nce

of

hyp

erte

nsi

on

(%

)

4 11

21

4454

64 65

Prevalensi HipertensiPrevalensi Hipertensi

Prevalensi :Prevalensi :

Berdasar kriteria Hipertensi WHO 1968 (tekanan darah > 160/95 mmHg), prevalensi hipertensi di dunia sekitar 5-18 %. Prevalensi hipertensi di Indonesia tidak jauh berbeda yaitu sekitar 6-15 %, walaupun dilaporkan adanya prevalensi yang rendah yaitu :

- Ungaran 1,8 %- Lembah Balim 0,6 %

serta adanya prevalensi yang tinggi :- Silungkang 19,4 %- Talang 17,8 %

Prevalensi Hipertensi di Jawa Timur hampir sama yaitu :- Sumberpucung (1976) 10 %- Lawang (1987) 11 %- Kampak (1987) 17 %

23%

16%

42%19%

Hypertensive patients who are treated but uncontrolled

Hypertensive patientswho are treated and controlled

Hypertensive patients who are unaware

Patients who are awarebut remain untreated

and uncontrolled

22 % of American adults 18 to 70 years of age have hypertension20 % of Indonesian adults have hypertension

New Criteria (WHO-ISH 1999) ≥ 140 / 90 mmHg

Source : Joffres et al. (1997) Am. J. Hypertension 10: 1097-1102

>>100100atauatau>> 160 160 Stage 2Stage 2

90-9990-99atauatau140-159140-159 Stage 1Stage 1


80-8980-89atauatau120-139120-139Pre HipertensiPre Hipertensi

<80<80dandan<120<120NormalNormal

DiastolicDiastolic(mm Hg)(mm Hg)

SystolicSystolic(mm Hg)(mm Hg)CategoryCategory

Klasifikasi Hipertensi (JNC 7 - 2003)Klasifikasi Hipertensi (JNC 7 - 2003)


Berdasarkan penyebabnya dapat dibedakan :

• Primer (essential)– tidak ada penyebab yang spesifik yang dapat

diidentifikasi– 90-95% dari kasus hipertensi

• Sekunder– diketahui penyebabnya– 5-10% dari kasus hipertensi– penyakit ginjal merupakan penyebab tersering

kasus hipertensi sekunder

Etiology HypertensionEtiology Hypertension• Secondary Hypertension :

– Renal disease :• Renal arterial disease• Renal parenchymal disease• Renal tumors• Arteritis (polyarteritis nodosa, neurofibromatosis)

– Endocrine Disorders• Cushing’s syndrome• Acromegaly• Primary aldosteronism• Pheochromocytoma

– Coarctation of the aorta– Neurologic disorders

• Increased intra cranial pressure (tumor)– Drug-induced hypertension

• Corticosteroids• Amphetamines• Oral contraceptives

– Psychogenic disorders

PATOPHYSIOLOGY

The factors affecting cardiac output: - sodium intake, renal function, & mineralocorticoids - the inotropic effects occur via extracellular fluid volume augmentation - an increase in heart rate and contractility

Peripheral vascular resistance is dependent upon the sympathetic nervous system, humoral factors, and local autoregulation

(Sharma, 2003)

Neurohormonal control of blood pressureBlood pressure = Cardiac output (CO) x Peripheral resistance (PR)

Hypertension = Increased CO and/or Increased PR

Preload

Fluid volume

Renal sodiumretention

Contractility

Fluid volume

Vasoconstriction

Sympatheticnervoussystem

Renin-angiotensin-aldosterone

system

Geneticfactors

Excesssodiumintake

(Adapted from Kaplan, 1994)

Hypertension :The Disease Continuum

Hypertension :The Disease Continuum

Early Paradigm

Elevated BP Target Organ Damage

Natural History of CVD ProgressionNatural History of CVD Progression

More Recent Paradigm

Vascular Dysfunction Elevated BP Target Organ Damage

A Proposed Future Paradigm

EndothelialDysfunction

LVHRenal

DamageMI Stroke

AnginaPectoris

VascularDysfunction

Elevated BP Target OrganDamage

?

Komplikasi HipertensiKomplikasi Hipertensi

Kerusakan yang disebabkan oleh hipertensi tergantung :

• Besarnya peningkatan tekanan darah

• Lamanya kondisi tekanan darah yang tidak terdiagnosis dan tidak diobati

Kerusakan Target Organ!!Eyesretinopathy

Kidneysrenal failure

Brainstroke

Heartischaemic heart disease

left ventricular hypertrophyheart failure

Peripheral arterial disease

Effects of blood pressure on the risk of cardiovascular disease

Average annual incidence rate per 10.000

Source : Framingham study (after Gorlin)

100

90

80

70

60

50

40

30

20

10

0

<100 120 140 180 >180

Systolic blood pressure (mmHg)

CHD

Stroke

CHF

SymptomsSymptoms

• Headache

• Dizziness

• Fatigue

• Pounding of the heartSymptoms are not specific and no more frequent than in patients with normotension.

• Symptoms of complications : heart failure, chest pain, claudication, vision

Evaluasi Klinis Hipertensi : Evaluasi Klinis Hipertensi :

Tujuan :

1. Konfirmasi hipertensi dan tingkatnya

2. Menyingkirkan & menemukan hipertensi sekunder

3. Menentukan kerusakan organ target

4. Mencari faktor risiko kardiovaskuler dan kondisi

klinik lain

Riwayat Klinis :Riwayat Klinis :

• Riwayat keluarga HT, DM, dislipidemia, PJK, stroke atau sakit ginjal

• Lama & tingkat TD sebelumnya & hasil Tx. serta efek

• Adanya PJK, gagal jantung, penyakit serebrovaskuler, ginjal, perifer, DM, pirai, dislipidemia, asma bronkhiale, & informasi obat

• Faktor risiko (diet lemak, Na & alkohol, rokok, aktifitas fisik, & BB)

• Riwayat obat-obatan (kontrasepsi, NSAID, kokain & amfetamin) dapat TD.

• Faktor pribadi, psikososial dan lingkungan.

Pemeriksaan Fisik :Pemeriksaan Fisik :

• Pemeriksaan fisik & TD yang teliti• Tinggi, berat, & BMI (Body mass Index) • Sistem kardiovaskuler : ukuran jantung,

gagal jantung, arteri perifer (carotis, aorta, renal)

• Paru (ronkhi & bronkhospasme), bising abdomen. • Fundus optikus & sistim syaraf (mengetahui

kerusakan serebro-vaskuler).

Technique of blood pressure measurement recommended by the British Hypertension Society

Technique of blood pressure measurement recommended by the British Hypertension Society

2.The patient should be relaxed and the arm must be supported. Ensure no tight clothing constricts the arm

3.The cuff must be level with the heart. If the circumference exceeds 33cm, a large cuff must be used (2/3 of arm). Place stethoscope diaphram over brachial artery

4.The column of mercury must be vertical. Inflate to occlude the pulse (>30 mmHg). Deflate at 2-3 mm/s. measure systolic ( first sound / Korotkoff I ) & diastolic (disappearence / Korotkoff IV or V ) to nearest 2 mmHg

(From British Hypertension Society 1985)

1.Several time, rest 5 minutes before

Recommended Technique for Measuring Blood Pressure

Standardized technique:

• Have the patient rest for 5 minutes

• Use an appropriate cuff size

• Use a mercury manometer or a recently calibrated electronic device

• Position cuff appropriately

• Increase pressure rapidly

• Support arm with antecubital fossa or heart level

• To exclude possibility of auscultatory gap, increase cuff pressure rapidly to 30 mmHg above level of diseappearance of radial pulse

• Place stethoscope over the brachial artery

Recommended Technique for Measuring Blood Pressure (cont.)

Recommended Technique for Measuring Blood Pressure (cont.)

• Drop pressure by 2 mmHg / beat:

- appearance of sound (phase I Korotkoff)

= systolic pressure

- disappearance of sound (phase V

Korotkoff) = diastolic pressure

• Take 2 blood pressure measurements, 1 minute apart

Diagnosis of Hypertension

Hypertension is defined as:

- BP 140/90 mm Hg- during 1-5 visits- with an average of 2 readings per visit

Pengukuran tekanan darah ambulatoryPengukuran tekanan darah ambulatory

Sekarang terdapat alat otomatis untuk mengukur tekanan darah selama 24 jam atau lebih.

Indikasi pemeriksaan tersebut (ABPM = Ambulatory Blood Pressure Monitoring) ialah sebagai berikut :

1. Adanya variasi tekanan darah yang besar

2. Office hypertension

3. Dicurigai adanya episode hipotensi

4. Hipertensi yang resisten terhadap pengobatan

Pemeriksaan lain-lainPemeriksaan lain-lain

• Laboratorium :• Urinalisis & mikroskopik urin• Serum kalium, kreatinin, gula darah puasa & 2 jam dan profil lemak,

asam urat• Pemeriksaan tambahan :

– Pemeriksaan hormonal seperti pengukuran aktifitas renin plasma, aldosteron plasma dan katekolamin urine atas indikasi khusus (hipertensi sekunder)

• EKG & Foto polos dada• Ekhokardiografi (curiga kerusakan organ target /LVH / lainnya)• Ultrasonografi vaskuler (curiga penyakit arteri karotis, aorta atau

perifer lain)• Ultrasonografi renal (curiga penyakit ginjal)• Angiografi

Minimal BP Goal of TherapyMinimal BP Goal of Therapy

Recommendations (SBP/DBP mmHg)

Patient Type

Uncomplicated HTN

Hypertension with diabetes mellitus

Heart failure

Hypertension with renal impairment†

JNC VI

< 140/90

< 130/85 < 130/80*

< 130/85

< 125/75

(Bakris GL, et al for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000) (JNC VI. Arch Intern Med. 1997)

*National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.†Proteinuria > 1 g/24h.

Terapi HipertensiTerapi Hipertensi

• Terapi Non-farmakologis

– Menurunkan berat badan (5-20 mmHg/10 kg)

– Latihan dan olah raga (4-9 mmHg)

– Menghindari alkohol yang berlebihan

– Mengurangi asupan garam (2-8 mmHg)

– Stop merokok

– Menurunkan asupan lemak jenuh

Lifestyle Modification

Modification Approximate SBP

reduction (range)

Weight reduction 5–20 mmHg/10 kg loss

Adopt DASH eating plan 8–14 mmHg

Dietary sodium reduction 2–8 mmHg

Physical activity 4–9 mmHg

Moderation of alcohol

consumption 2–4 mmHg

Terapi HipertensiTerapi Hipertensi

• Terapi Farmakologis– tujuan terapi antihipertensi

• Memperbaiki fungsi endothel• untuk menurunkan resistensi vaskular sistemik• mempertahankan curah jantung• mempertahankan suplai darah ke organ dan

jaringan– Pengobatan diberikan seumur hidup– Kepatuhan yang buruk merupakan penyebab

kegagalan terapi antihipertensi yang paling besar

Pilihan terapi antihipertensiPilihan terapi antihipertensi

Diuretik

Beta-blocker

Antagonis kalsium

ACE-inhibitor

Angiotensin II receptor antagonis (AIIRA / ARB)

Alpha1-blocker (sentral & perifer)

Possible combinations of different classes of antihypertensive agents. The most rational combinations are represented as thick lines.ACE, angiotensin-converting enzyme; AT1, angiotensin II type 1.

ACE inhibitorsACE inhibitors

DiureticsDiuretics

11-blockers-blockers

-blockers-blockersATAT11 receptor receptor

blockersblockers

CalciumCalciumantagonistsantagonists

Algorithm for Treatment of HypertensionAlgorithm for Treatment of Hypertension

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140–159 or DBP 90–99

mmHg) Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.

Consider consultation with hypertension specialist.

Reasons of inadequate BP ControlReasons of inadequate BP Control

• Acceptance of inadequate control by physician

• Difficulty achieving BP control with one agent/suboptimal

regimens

• BP goals are more aggressive than in previous years

• Lack of compliance due to :

– perceived side effects of antihypertensive

medication(s)

– frequency of dosing/multiple agents to attain control

(Adapted from JNC VI. Arch Intern Med. 1997)

Presentasi pasien hipertensi yang terkontrol

Presentasi pasien hipertensi yang terkontrol

Adapted from G. Mancia / L. Ruilope

USA: JNC VI. Arch Intern Med 1997Canada: Joffres et al. Am J Hypertens 1997 England: Colhoun et al. J Hypertens 1998France: Chamontin et al. Am J Hypertens 1998

< 140/90 mmHg< 140/90 mmHg

Canada

16

USA

27

England6

France

24

Marques-Vidal P et al. J Hum Hypertens 1997

< 160/95 mmHg< 160/95 mmHg

Finland

20.5

Spain

20

Australia

19

Germany

22.5

> 65 years

Scotland

17.5

India

9

WHO-ISH (1999) WHO-ISH (1999)

Klasifikasi Derajat Tekanan Darah menurut WHO-ISH 1999 yang diadaptasi dari JNC VI 1997

Kategori Sistolik Diastolik (mmHg) (mmHg)

1 Optimal 120 80

2 Normal 130 85

3 Normal Tinggi 130 - 139 85 - 89

4 Hipertensi derajat 1 (ringan) 140 - 159 90 - 99Subgrup : perbatasan 140 - 149 90 - 94

5 Hipertensi derajat 2 (sedang) 160 - 179 100 - 109

6 Hipertensi derajat 3 (berat) 180 110

7 Hipertensi Sistolik 140 90(Isolated Systolic Hypertension)

HipertensiHipertensi• Secondary Hypertension :

Renal diseaseRenal disease Interference with renal control systems over cardiovascularInterference with renal control systems over cardiovascularsystem - activation of renin-angiotensin-aldosterone (RAA)system - activation of renin-angiotensin-aldosterone (RAA)system, leading to increased blood volume & hence hypertensionsystem, leading to increased blood volume & hence hypertension

Renal arteryRenal artery Atherosclerotic narrowing of decreased vasodilatory mechanismsAtherosclerotic narrowing of decreased vasodilatory mechanismsstenosisstenosis leading to reduced renal blood flow and activation of RAA systemleading to reduced renal blood flow and activation of RAA system

Endocrine disordersEndocrine disordersHyperaldosteronismHyperaldosteronism Excessive aldosterone production leading to salt and waterExcessive aldosterone production leading to salt and water(Conn’s syndrome)(Conn’s syndrome) retention and increased blood volumeretention and increased blood volumeCushing’s syndromeCushing’s syndrome Excessive ACTH secretion leading to salt and water retention andExcessive ACTH secretion leading to salt and water retention and

increased blood volumeincreased blood volume

PhaeochromocytomaPhaeochromocytoma Tumour of the adrenal medulla producing excessive adrenaline,Tumour of the adrenal medulla producing excessive adrenaline,causing vasoconstrictioncausing vasoconstriction

PregnancyPregnancy Complex, involving fluid volume and hormonal fluctuationsComplex, involving fluid volume and hormonal fluctuations

Coarctation of theCoarctation of the Congenital localised narrowing of the aortic lumen, causingCongenital localised narrowing of the aortic lumen, causingaortaaorta increased afterload and peripheral resistance in the upper bodyincreased afterload and peripheral resistance in the upper body

Certain drugs,Certain drugs, Complex and variousComplex and variouse.g. corticosteroids,e.g. corticosteroids,oral contraceptivesoral contraceptivesand vasoconstrictorsand vasoconstrictors

Renin inhibitorsRenin inhibitors

AII receptor blockersAII receptor blockers

Angiotensin IIAngiotensin II

ReninRenin

Converting enzymeConverting enzyme

Angiotensinreceptors

AngiotensinogenAngiotensinogen

ACE inhibitorACE inhibitor

Angiotensin IAngiotensin I

LiverLiver TissueTissueCirculatingCirculating LocalLocal

Non Renin pathways - t-PA - Cathepsin G - Tonin

Non-ACE pathways - Chymase - CAGE - Cathepsin G

The Renin-Angiotensin SystemThe Renin-Angiotensin SystemAlternate PathwayAlternate Pathway

Brown, M.J., Lancet 2000;355:653-4

Risiko Infark Miokard dan Stroke Risiko Infark Miokard dan Stroke

Systolic blood pressure (mm Hg)

5-ye

ar r

isk

(%)

0

5

10

15

0 100 200 300

StrokeStrokeMIMI

CHFCumulativeIncidence

(%)

Years From Baseline Exam

5 10 15

20

15

10

5

0

Lenfant C, Roccella EJ. J Hypertens Suppl. 1999;17:S3-S7.Data from Levy D et al. JAMA. 1996;275:1557-1562.

Stage 2+ hypertension

Stage 1+ hypertension

Normal BP

Cumulative Incidence of CHF : Normotensives and Stage 1 and 2 Hypertensives

Cumulative Incidence of CHF : Normotensives and Stage 1 and 2 Hypertensives

Effects of Angiotensin II at ATEffects of Angiotensin II at AT11 and AT and AT22 ReceptorsReceptors

Blocked by ARB s

ATAT2AT1

- 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;84:3S–8S.

Role of A II in Vascular Disease

Reprinted with permission from Dzau VJ. Hypertension. 2001;37:1047-1052.

Diabetes Smoking

Oxidative Stress

Endothelial Dysfunction and Smooth Muscle Activation

Growth FactorsCytokines

Matrix

Proteolysis Inflammation

VCAM/ICAMCytokines

EndothelinCatecholamines

BP LDL

NO • ∆ Local Mediators • Tissue ACE, AII

PAI-1, Platelet Aggregation, Tissue Factor

Vasoconstriction Thrombosis Inflammation Plaque RuptureVascular Lesion and Remodeling

Clinical Sequelae

Risk Factors

Target Organ Damage Target Organ Damage

Heart• Left ventricular hypertrophy• Angina or prior myocardial infarction• Prior coronary revascularization• Heart failure

Brain• Stroke or transient ischemic attack

Chronic kidney disease

Peripheral arterial disease Retinopathy

Khattar, R.S. et al. Circulation 1999; 100:1071-4

Assessment of the 24-hour blood pressure load isa good clinical method to identify high-risk patients

even

ts/1

00 p

t/yr

s

200+

mm Hg

< 140 140-159 160-179 180-199

1

2

3

4

5

6

7

Systolic Blood PressureSystolic Blood Pressure

Total Mortality and Continuous Ambulatory Blood Pressure

Total Mortality and Continuous Ambulatory Blood Pressure

1

2

3

4

5

Diastolic Blood PressureDiastolic Blood Pressure

mm Hg

< 80 80-89 90-99 100-109 110+

Benefits of Lowering BPBenefits of Lowering BP

Average Percent Average Percent

ReductionReduction

Stroke incidence Stroke incidence 35–40% 35–40%

Myocardial infarction Myocardial infarction 20–25% 20–25%

Heart failureHeart failure 50% 50%

Goals of Therapy(JNC-VII)

Goals of Therapy(JNC-VII)

Reduce CVD and renal morbidity and mortality.

Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.

Achieve SBP goal especially in persons >50 years of age.

Hypertension Prevalence and Treatment :

North America and EuropePrevalence of Hypertension

0

5

10

15

20

25

30

35

40

45

50

55

Country

%

USCanada

Germany

ItalySwedenEnglandSpainFinland

0

10

20

30

40

50

60

70

80

90

100

Country

%

Wolf-Maier K et al. JAMA. 2003;289:2363-2369.

Patients on Therapy

25% 12.5%

12.5%

50%

Hypertensive patients who are treated but uncontrolled

Hypertensive patientswho are treated and controlled

Hypertensive patients who are unaware

Patients who are awarebut remain untreated

and uncontrolled

Source : Joffres et al. (1997) Am. J. Hypertension 10: 1097-1102

RULE OF HALF

BP Control Rates

Trends in awareness, treatment, and control of high blood pressure in adults ages 18–74

National Health and Nutrition Examination Survey

Percent

II

1976–80

III(Phase 1)1988–91

III(Phase 2)1991–94 1999–2000

Awareness 51 73 68 70

Treatment 31 55 54 59

Control 10 29 27 34

Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

Antihypertensive Agents Combination

ACE INHIBITOR

DIURETIC

AT-2 RB

Ca-ANTAGONIST-BLOCKER

-BLOCKER

ESC-ESH 2003

CVD Risk FactorsCVD Risk Factors

Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus* Microalbuminuria or estimated GFR <60 ml/min Age (older than 55 for men, 65 for women) Family history of premature CVD

(men under age 55 or women under age 65)

* Components of the metabolic syndrome.

Classification and Management of BP for adults

Classification and Management of BP for adults

* Treatment determined by highest BP category.† Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

Two-drug combination for mostTwo-drug combination for most†† (usually thiazide-type diuretic (usually thiazide-type diuretic and ACEI or ARB or BB or and ACEI or ARB or BB or CCB).CCB).

YesYes or or >>100100 >>160160 Stage 2 Stage 2 HypertensionHypertension

Drug(s) for the Drug(s) for the compelling indications.compelling indications.‡‡

Other antihypertensive Other antihypertensive drugs (diuretics, ACEI, drugs (diuretics, ACEI, ARB, BB, CCB) as ARB, BB, CCB) as needed. needed.

Thiazide-type diuretics for most. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, May consider ACEI, ARB, BB, CCB, or combination.CCB, or combination.

YesYes or 90–99or 90–99 140–159140–159 Stage 1 Stage 1 HypertensionHypertension

Drug(s) for compelling Drug(s) for compelling indications. indications. ‡‡

No antihypertensive drug No antihypertensive drug indicated.indicated.

YesYes or 80–89or 80–89 120–139120–139 PrehypertensionPrehypertension

EncourageEncourage and <80and <80 <120<120 NormalNormal

With compelling With compelling indicationsindications

Without compelling Without compelling indication indication

Initial drug therapyInitial drug therapy Lifestyle Lifestyle

modificationmodification DBP* DBP*

mmHgmmHg SBP* SBP*

mmHgmmHg BP classificationBP classification

Compelling Indications for Individual Drug Classes


Clinical Trial BasisClinical Trial BasisInitial Therapy OptionsInitial Therapy Options Compelling IndicationCompelling Indication

ALLHAT, HOPE, ALLHAT, HOPE, ANBP2, LIFE, ANBP2, LIFE, CONVINCECONVINCE

ACC/AHA Post-MI ACC/AHA Post-MI Guideline, BHAT, Guideline, BHAT, SAVE, Capricorn, SAVE, Capricorn, EPHESUSEPHESUS

ACC/AHA Heart Failure ACC/AHA Heart Failure Guideline,Guideline, MERIT-HF, MERIT-HF, COPERNICUS, CIBIS, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, SOLVD, AIRE, TRACE, ValHEFT, RALESValHEFT, RALES

THIAZ, BB, ACE, CCBTHIAZ, BB, ACE, CCB

BB, ACEI, ALDO ANTBB, ACEI, ALDO ANT

THIAZ, BB, ACEI, ARB, THIAZ, BB, ACEI, ARB, ALDO ANTALDO ANT

High CAD riskHigh CAD risk

PostmyocardialPostmyocardialinfarctioninfarction

Heart failureHeart failure



Recurrent stroke Recurrent stroke preventionprevention

Chronic kidney diseaseChronic kidney disease

DiabetesDiabetes

Clinical Trial BasisClinical Trial BasisInitial Therapy OptionsInitial Therapy Options Compelling IndicationCompelling Indication

PROGRESSPROGRESS

NKF Guideline, NKF Guideline, Captopril Trial, Captopril Trial, RENAAL, IDNT, RENAAL, IDNT, REIN, AASKREIN, AASK

NKF-ADA Guideline,NKF-ADA Guideline, UKPDS, ALLHATUKPDS, ALLHAT

THIAZ, ACEITHIAZ, ACEI

ACEI, ARBACEI, ARB

THIAZ, BB, ACE, ARB, THIAZ, BB, ACE, ARB, CCBCCB

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3 Hipertensi