lecture 2_dr wurjanto

7/31/2019 Lecture 2_dr Wurjanto

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Pengelolaan Hipertensi

dr. Wuryanto, SpPD-KGH


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Topik

Latar Belakang; Mengapa harus diturunkan?

CV Assessment

Definisi hipertensi

Compelling indication Target tekanan darah

Algoritme

Pengobatan non-farmakologik

Pilihan obat hipertensi


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Mengapa tekanan darah

harus diturunkan ?


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Lewington S, et al. Lancet. 2002;360:1903-1913;

Chobanian AV, et al.JAMA. 2003;289:2560-2572.

Cardiovascular Mortality RiskIncreases as Blood Pressure Rises*

Cardiovascular

MortalityRisk

Systolic/Diastolic Blood Pressure (mm Hg)

0

1

2

3

4

5

6

7

8

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

2x

4x

8x

*Measurements taken in individuals aged 4069 years, beginning with a bloodpressure of 115/75 mm Hg.

Slide Source

Hypertension Onlinewww.hypertensiononline.org


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*Defined as death due to cardiovascular disease or as having recognizedmyocardial infarction, stroke, or congestive heart failure.

CumulativeIn

cidenceofM

ajor

CardiovascularEvents(%

) 16

12

10

8

6

4

2

0

14

0 2 4 6 8 10 12

Time (Years)

Optimal


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From Lewington S, Clarke R, Qizilbash N, et al: Age-specific relevance of usual blood pressure

to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospectivestudies. Lancet 360:19031913, 2002Slide Source



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Complicationsof Hypertension:End-Organ Damage

Chobanian AV, et al.JAMA. 2003;289:2560-2572.

Peripheral

VascularDisease Renal Failure,

Proteinuria

LVH, CHD, CHFHemorrhage,

Stroke

Retinopathy

CHD = coronary heart diseaseCHF = congestive heart failureLVH = left ventricular hypertrophy

Hypertension

Slide Source



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0

5

10

15

20

25

30

Antihypertensive Treatment Can Reduce Cardiovascular Events in DiabeticPatients

Hypertension Optimal Treatment Study

Hansson L, et al. Lancet. 1998;351:17551762.

EventsP

er1000Pa

tient-Years

P= 0.005

Events include all myocardial infarctions, allstrokes, and all other cardiovascular deaths.

Target

DBP

(mm Hg)

Achieved

SBP*

(mm Hg)

Achieved

DBP*

(mm Hg)

Patientswith

Diabetes

90 143.7 85.2 501

85 141.4 83.2 501

80 139.7 81.1 499

*Mean of all blood pressures for all studypatients in the blood pressure subgroups from6 months of follow-up to the end of the study.

DBP = diastolic blood pressure

SBP = systolic blood pressure

Slide Source



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Absolute and relative risk for a cardiovascular disease event in a high- and low-risk 55-year oldman by systolic blood pressure. See text. (From Lewington S, Clarke R, Qizilbash N, et al: Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data

for one million adults in 61 prospective studies. Lancet 360:19031913, 2002.) Slide SourceHypertension Online

www.hypertensiononline.org


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O2 Endothelial Cells and

H2O2 Vascular Smooth Muscle

Oxidative Stress: EndothelialDysfunction and CAD/Renal Risk Factors

Endothelial Dysfunction

Apoptosis

VasoconstrictionLeukocyteadhesion

Lipiddeposition

ThrombosisVSMCgrowth

HypertensionSmokingDiabetes LDL

Homocysteine Estrogendeficiency

Slide Source



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2009 Canadian Hypertension Education ProgramRecommendations

Over 90% of hypertensive have other cardiovascularrisks

Assess and manage hypertensive patients fordyslipidemia, dysglycemia (e.g. impaired fasting

glucose, diabetes) abdominal obesity, unhealthyeating and physical inactivity

Assessment of the overall cardiovascular risk

Slide Source



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2009 Canadian Hypertension Education ProgramRecommendations

Search for target organ damage

Cerebrovascular disease- transient ischemic attacks

- ischemic or hemorrhagic stroke

- vascular dementiaHypertensive retinopathy

Left ventricular dysfunction

Left ventricular hypertrophy

Coronary artery disease

- myocardial infarction

- angina pectoris

- congestive heart failure

Chronic kidney disease

-hypertensive nephropathy (GFR < 60ml/min/1.73 m2)

- albuminuria

Peripheral artery disease

- intermittent claudication

- ankle brachial index < 0.9


Slide SourceHypertension Onlinewww.hypertensiononline.org


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2009 Canadian Hypertension Education Program

Recommendations

Search for exogenous potentially modifiable factors that caninduce/aggravate hypertension

Prescription Drugs:

NSAIDs, including COXIBS (e.g. celecoxib)

Corticosteroids and anabolic steroids

Oral contraceptive and sex hormones

Vasoconstricting/sympathomimetic decongestants

Calcineurin inhibitors (cyclosporin, tacrolimus)

Erythropoietin and analogues

Monoamine oxidase inhibitors (MAOIs)

Other sympathomemetics e.g. Midodrine

Other:

Licorice root

Stimulants including cocaine

Salt

Excessive alcohol use

Sleep apnea


Slide SourceHypertension Online



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Category Systolic Diastolic

120 and 80

120-129 and/or 80-84

High Normal 130-139 and/or 85-89

Grade 1 Hypertension 140-159 and/or 90-99

Grade 2 Hypertension 160-179 and/or 100-109

Grade 3 Hypertension 180 and/or 110

Isolated SystolicHypertension

140 and 90

ESH/ESC Definition and Classification of Blood

Pressure Levels (mm Hg)

Mancia G, et al. J Hypertens 2007;25:1105-1187

Optimal

Normal

Slide SourceHypertension Onlinewww.hypertensiononline.org


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Very highadded risk

Highadded risk

Highadded risk

Highadded risk

Moderateadded risk

3 risk factors,mets, organ

damage, or diabetes

Very highadded risk

Very highadded risk

Very highadded risk

Very highadded risk

Very highadded risk

Established CV orrenal disease

Very highadded risk

Moderateadded risk

Moderateadded risk

Low addedrisk

Low addedrisk

1-2 risk factors

High addedrisk

Moderateadded risk

Low addedrisk

Averagerisk

Averagerisk

No other risk factors

Grade 3 HTGrade 2

HTGrade 1

HTHigh

normalNormal

Other risk factor,organ damage, ordisease

Blood pressure (mm Hg)

HT: hypertension; mets: metabolic syndrome; CV: cardiovascular

Mancia G, et al. 2007 ESH/ESC Guidelines for the Management of Arterial Hypertension. J Hypertens 2007;25:1105-1187

Cardiovascular Risk Stratification


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A gradual reduction in blood pressure is

desirable in hypertensive patients in

general, particularly in elderly patients,

Target control level should be achieved

within a few weeks in high-risk patients,

such as those with grade III hypertensionand multiple risk factors.

Japan Society of Hypertension 2009

Target Pengobatan


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mm Hg

UncomplicatedHypertension

Chronic Kidney DiseaseCoronary Artery Disease

Diabetes

140

90

130

80

SystolicBlood

Pressure

DiastolicBloodPressure

Current Blood Pressure Targets for VariousChronic Conditions

American Diabetes Association. Diabetes Care. 2003;26:S80-S82;Hansson L, et al. Lancet. 1998;351:1755-1762; National KidneyFoundation.Am J Kidney Dis. 2002;39(2 Suppl 1):S1-S266;

Rosendorff C, et al. Circulation. 2007;115:2761-2788.

Slide Source



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TERAPI HIPERTENSI

Non-farmakologik

Farmakologik

JNC VII 2004: berjenjang dan compelling indications

BHS-NICE 2006 : terapi sekuensial

Pengobatan awal dan kombinasi :

ESH-ESC 2009, CHEP 2009, JHS 2009

M difik i hid k


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Modifikasi gaya hidup untukpengendalian Hipertensi

Modifikasi Rekomendasi Penurunan Tekanan DarahSistolik kurang lebih

Menurunkan berat

badan

Pelihara berat badan normal

(BMI 18.5-24.9)5-20 mm Hg utk setiappenurunan 10 kg BB

Menjalankan menuDASH

Konsumsi makanan kaya buah,sayur, susu rendah lemak danrendah lemak jenuh

8-14 mm Hg

Mengurangi asupan

garam/sodium

Kurangi natrium sampai tidak

lebih dari 2.4 g/hari atau NaCl 6

g/hari

2-8 mm Hg

Meningkatkan aktifitasfisik

Berolahraga erobik teraturseperti misalnya berjalan kaki

(30 men/hari 4-5 hari

seminggu)

4-9 mm Hg

Kurangi konsumsi

alkohol

Batasi konsumsi alkohol,jangan

lebih dari 2 /hari utk pria dan 1

/hari utk perempuan.

2-4 mm Hg

Source: The Seventh Report of the Joint National Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure JNCVII. JAMA. 2003;289:2560-2572.
http://c/Documents%20and%20Settings/Administrator/Local%20Settings/Temp/DASH.txthttp://c/Documents%20and%20Settings/Administrator/Local%20Settings/Temp/DASH.txt


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Choose between:

Single agentat low dose

Two-drug combinationat low dose

If goal BP not achieved

Previous agentat full dose

Switch to differentagent at low dose

Previous combinationat full dose

Add a third drugat low dose

Two-three-drug combinationat effective doses

Two- to three-drugcombination

Full-dosemonotherapy

If goal BP not achieved

BP, blood pressure

Mild BP elevationLow/moderate CV risk

Conventional BPtarget

Marked BP elevationHigh/very high CV risk

Lower BP target

ESH/ESC Guidelines 2007

European Heart Journal. 2007;28:1462-1536

Hypertension treatment strategy: ESH/ESC 2007


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Follow-up of blood pressureabove targets

Patients with blood pressure above target arerecommended to be followed at least every 2nd month

Follow-up visits are used to increase the intensity of

lifestyle and drug therapy, monitor the response totherapy and assess adherence


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History of antihypertensive drugs

Directvasodilators

Alpha-blockers

Peripheralsympatholytics

Ganglion

blockers

Veratrumalkaloids

Central 2agonists

Calciumantagonists-non-DHPs

Beta-blockers

Thiazidediuretics

Calciumantagonists-

DHPs

ARBs

1940s 1950 1957 1960s 1970s 1980s 1990s 2000 2007

ACEinhibitors

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

Effectiveness and general tolerability

DRI


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Main classes of antihypertensive drugs

Diuretics Inhibit the reabsorption of salts and water from kidney tubules into thebloodstream

Calcium-channel antagonists

Inhibit influx of calcium into cardiac and smooth muscle

Beta-blockers

Inhibit stimulation of beta-adrenergic receptors

Angiotensin-converting enzyme (ACE) inhibitors

Inhibit formation of angiotensin II

Angiotensin II receptor blockers (ARBs)

Inhibit binding of angiotensin II to type 1 angiotensin II

Receptors

Vasodilators

Direct renin inhibitors


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JAPAN HYPERTENSION SOCIETY 2009Treatments of Hypertension

1. The antihypertensive drug to be first administered alone orconcomitantly with other drugs should be selected from Cachannel blockers, angiotensin-receptor blockers(ARBs),angiotensin-converting enzyme (ACE) inhibitors, diureticsand b-blockers.

2. Appropriate antihypertensive drugs should be selectedconsidering positive indications, contraindications, conditionsthat require the careful use of drugs and the presence or absenceof complications.

3. Administered once a day, but as it is more important to control theBP over 24 h, splitting the dose into twice a day is desirable insome situations.


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1-blockers

2007 ESH/ESC Guidelines

CCBs

Diuretics

ACE inhibitors

AT1-receptorblockers-blockers


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Treatment of hypertension

Each drug class has contraindications aswell favorable effects in specific clinicalsettings. The choice of drug(s) should bemade according to this evidence.

The traditional ranking of drugs into first,second, third, and subsequent choice, withan average patient as reference, has nowlittle scientific and practical justificationand should be avoided

Mancia et al. Reappraisal of ESH-ESC Guidelines 2009


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Thiazide Diuretics

Thiazides

Veins

Mechanism: inhibit Na/K pumps in

the distal tubule

Examples:

Hydrocholorthiazide 12.5-25 mg daily

Chlorthalidone 12.5-50 mg daily

Effective first line agent and

provides synergistic benefit

As single agent more effective if

CrCl >30 ml/min

Compelling indications: HF, High

CAD risk, Diabetes, Stroke, ISH


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Loop Diuretics

ThiazidesLoops

Veins

Mechanism: Inhibit Na/K/Cl ATPase

in ascending loop of henle

Examples:

Furosemide 20 mg BID

Typically only beneficial in patientswith resistant HTN and evidence of

fluid; effective if CrCl


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Aldosterone Receptor Antagonists

ThiazidesLoops

Aldosterone Ant.

Veins

Mechanism: inhibit aldosterones

effect at the receptor, reducing Naand water retention

Examples:

Spironolactone 25 mg daily

Can provide as much as 25 mmHg

BP reduction on top of 4 drug

regimen in resistant hypertension

Monitor SCr and K

Compelling indications: HF

Am J Hypertension. 2003; 16:925-930.


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Beta Blockers

Beta Blockers

Heart

Mechanism: Competitively inhibitthe binding of catecholamines to

beta-adrenergic receptors

Examples:

Atenolol 25-100 mg QD, Metoprolol 25 -100 mg BID, Bisoprolol 2.5 10 mg QD

Carvedilol 6.25-50 mg (alfa+Beta)BID

Monitor: HR, Blood Glucose in DM

Not contraindicated in asthma or

COPD but use caution

Compelling indications: HF, post-MI,

High CAD risk, Diabetes


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Calcium Channel Blockers Non-Dihydropyridine:Diltiazem and Verapamil

DiltiazemVerapamil

Heart

Mechanism: Decrease calcium

influx into cells of vascular smoothmuscle and myocardium

Examples:

Diltiazem Long acting; CD 100 -400 mg

Verapamil 60-480 mg, long acting SR

Monitor: HR

Verapamil causes constipation

Relatively contraindicated in heart

failure

Compelling indications: Diabetes,

High CAD risk

Arteries


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Calcium Channel Blockers: Dihydropyridine

DihydropyridineCCBs

Arteries

Mechanism: Decrease calcium

influx into cells of vascular smoothmuscle

Examples:

Amlodipine 2.5-10 mg PO daily

Felodipine 2.5-10 mg PO daily

OROS/GITS. Do not use immediate

release nifedipine

Monitor: Peripheral edema, HR (cancause reflex tachycardia)

Good add on agent if cost is not an

issue


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ACEI

ACEI

Mechanism: Inhibit vasoconstriction by

inhibiting synthesis of angiotensin II;provides balanced vasodilation

Examples:

ACEI: Captopril 12.5 -50 BID, Enalapril 2.5-40 mg dailyBID, Lisinopril 5 40 mg daily,

Imidapril 5-10 QD, Perindopril 4-8 mg QD,

Ramipril 2.5-20 mg

Monitor: S Cr, K


High CAD risk, Diabetes, CKD, Stroke

Arteries Veins


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Renin-Angiotensin Cascade

Angiotensinogen

Angiotensin I

Angiotensin II

AT1 AT2 ATn

Bradykinin

Inactivepeptides

Non-renin(eg tPA)

Non-ACE(eg chymase) ACE

Renin




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ARBs

ARB

Mechanism: Inhibit vasoconstriction by

blocking action of angiotensin II;provides balanced vasodilation

Examples:

ARB: Irbesartan 150-300 mg QD, Losartan25-100 mg BID, Olmesartan 20-40 mg,

Telmisartan 20-80 mg, Valsartan 90-160

mgQD

Monitor: S Cr, K


High CAD risk, Diabetes, CKD, Stroke

Arteries Veins


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Angiotensin II (Ang II) generatedin the afferent arteriole interactswith AT1 receptors on cellularcomponents of the nephron

Angiotensinogen Ang I

Renin

ACEAng II

AT1R

= AT1 Receptor




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Pathologic Processes Leading toGlomerular Injury and Proteinuria

Ang II

Increasedglomerularpressure

Ang II

Urinary proteinGlucose

AGEs

Glycoxidation(glycation)

Efferentarteriolarconstrictio

n

=angiotensinAT1 receptor

Slide Source



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Alpha1 Blockers

Alpha1 Blockers

Arteries

Mechanism: Inhibit peripheral post-

synaptic alpha1 receptors causingvasodilation

Examples:

Terazosin 1 20 mg daily

Doxazosin 1 16 mg daily

Cause marked orthostatic

hypotension, give dose at bedtime

Consider only as add on therapy

Can be beneficial in patients with

BPH


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Central Acting Agents

Central ActingMechanism:

Clonidine

Heart Mechanism: false neurotransmittersreduce sympathetic outflow

reducing sympathetic tone

Examples:

Clonidine 0.75-0.6 mg bid, Methyldopa

250 mg-1000 mg BID (Pregnancy),

Reserpin 0,1 -0,25 mg QD

Monitor: HR (bradicardia)

Side effects often limiting: Dry

mouth, orthostasis, sedation

Withdrawal/Rebound effect


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Vasodilators

DihydropyridineCCBs

Hydralazine

Minoxidil

Arteries

Mechanism: Direct vasodilation of

arterioles via increased intracellularcAMP

Examples:

Hydralazine 20-400 mg BID-QID

Minoxidil 2.5-40 mg PO daily-BID

Monitor: HR (can cause reflex

tachycardia), Na/Water retention

Hydralazine is an alternative in HF ifACEI contraindicated

Consider minoxidil in refractory

patients on multi-drug regimens

NEW ANTIHYPERTENSIVE


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Direct Renin Inhibitor; ALISKIRENMonotherapy effective in lowering SBP and DBP

in hypertensive patients

Effective also in combination with a thiazidediuretic, a CCB and an ACE inhibitor or an ARB

Protect against subclinical organ damage when

combined with an ARB= the available evidence justifies its use in hypertension, in

combination with other agents.

Mancia et al.Reappraisal of ESC Hypertension Guidelines 2007

NEW ANTIHYPERTENSIVEAGENTS


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Aliskiren reduces Ang I, Ang II and PRA

AliskirenARBACEI

PRAReninAng IIAng I

Feedback Loop

AT1 Receptor

ReninAng I

Angiotensinogen

Ang II

Direct renin inhibitor

ARBs

ACE

Non ACE pathways

ACEIs