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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
Hypertension Onlinewww.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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
Assessment of the overall cardiovascular risk
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
Assessment of the overall cardiovascular risk
Slide SourceHypertension Online
www.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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.txt7/31/2019 Lecture 2_dr Wurjanto
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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
Compelling indications: HF, post-MI,
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
Slide SourceHypertension Online
www.hypertensiononline.org
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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
Compelling indications: HF, post-MI,
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
Slide SourceHypertension Online
www.hypertensiononline.org
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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
Hypertension Onlinewww.hypertensiononline.org
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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