Hipertensi
Hipertensi
Lukman Muliadi
Hipertensi bisa menyerang anak-anak atau orang dewasa, namun umumnya pada orang dewasa di atas 35 tahun
BP CLASSIFICATION
ESH-ESC & WHO-ISH 2003 BP Classification Optimal Normal High normal Grade 1 Hypertension (mild) Grade 2 Hypertension (moderate) Grade 3 Hypertension (severe) Isolated Systolic Hypertension Systolic BP <120 / <80 120-129 / 80-84 130-139 / 85-89 140-159 / 90-99 160-179 /100-109 > 180 / >110 Isolated Systolic Hypertension Diastolic BP <120/<80 120-129 /80-84 130-139 / 85-89 140-159 / 90-99 >160 / >100 Stage 1 Hypertension Stage 2 Hypertension JNC VII Bp Classification Normal Prehypertension
> 140
< 90
Hypertension Syndrome Its More Than Just Blood Pressure (Tidak hanya tekanan darah yang meningkat)
Decreased Arterial Compliance
Obesity
Hypertension
Neurohormonal Dysfunction
Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens. 1991;5:417-423. Dzau VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5.
Hypertension Linked To Chronic Renal Disease Among 332,544 Men Screened for MRFIT
250 250 200 200
<80
hipertensi
(patogenesis)
TEKANAN DARAH = CURAH JANTUNG x RESAISTENSI PERIFERA
Hipertensi
Preload K ontraktilitas
Peningkatan CJ
Peningkatan RP
Hipertrofi struktural
Konstriksi Fungsional
Volume Cairan
Redistribusi Cairan
RAS
Hiper insulinemi
Obesitas
EDF
Normotensi
HIPERTENSI DINI
HIPERTENSI (KLINIS)
TANPA KOMPLIKASI
DENGAN KOMPLIKASI
Hipertensi Maligne
Age Group
x3
x4.5
x9 x16
.x1,6 Smoking
x6
x4
Serum cholesterol level (8.5 mmol/L, 330 mg/dL)
Systolic BP is a better indicator of CAD risk than diastolic blood pressure (DBP)
MRFIT*: CAD death and BP
Age-adjusted CAD death rate per 10,000 person-years
100 90 80 70 60 50 40 30 20 10 0
Systolic BP
DBP
150 90
*Multiple Risk Factor Intervention Trial. Adapted from Neaton et al, Arch Intern Med, 1992.
170 100 mm Hg
190 110
210 120
8 7 6 5 4 3 2 1 0
Systolic BP DBP
Systolic BP DBP
<112 <71
11271-
11876-
12179-
12581-
12984-
13286-
13789-
14292-
151 98
mm Hg
300
CVD deaths per 10,000 person-years
250
Patients without diabetes
200
150
100
50
0
<120 120-139 140-159 160-179 180-199 Systolic BP (mm Hg)
Stamler et al, Diabetes Care, 1993.
200
prevent 1 death
for every 11 patients treated.
JNC VII 2003
Millimetres matter
Millimetres matter
A 2-mmHg reduction in DBP would result in a 6% reduction in the risk of CHD and a 15% reduction in the risk of stroke and TIAs
DBP, diastolic blood pressure; CHD, coronary heart disease; TIA, transient ischaemic attack
Cook NR, et al. Arch Intern Med 1995;155:701-709
Relative importance of SBP and DBP as predictors of CHD risk as a function of age
1.0 0.5 0.0 p=0.008 Favours DBP 45 55 Age (years)
Favours SBP
25
35
65
75
* The difference between SBP and DBP proportional hazard regression coefficients, ie, (SBP) - (DBP), was estimated for each age group SBP, systolic blood pressure; DBP, diastolic blood pressure; CHD, coronary heart disease
Myocardial Ischemia
Coronary Artery Disease LV Hypertrophy Atherosclerosis
Remodelling
Sudden Death
Ventricular Dilatation
Heart Failure
Risk factor :
Hypertension Hyperlipidemia Diabetes Insulin resistance
Death
Dzau & Braunwald , 1991
Kidney
Renal Insufficiency ESRD / Gagal Gnjal
Heart
Left Ventricular Hypertrophy
Chronic Heart Failure Myocardial Infarction Congestive Heart Disease Arrhythmia
Hypertension
Brain
Stroke
Vessel
Arteriosclerosis Peripheral Vascular Disease Coronary Heart Disease
The pioneers
Vasodilation treatment with fever-producing or antimalarial agents : Fries 1940s:
This was the first time we had seen reversal of the signs of malignant hypertension following an antihypertensive drug. It was an exciting experience
Page
1949 :
I need hardly say this an unpleasant treatment butconsidering the danger of the diseaseto the life of the patient it is a small price to pay for the benefits
Year
1935 1937 19371941
Blood pressure
162/98
Complications Treatment
136/78 (age 53) Phenobarbital Low salt and low fat diet/massages/digitalis
170-180/90-100
1941
188/105
186/108 180-230/110-126
TDS(mmHg)
+20.2 +16.0 +12.0 +11.5 +9.5 +8.8 +5.9 +1.9 +0.3 0.0 -10.0
TDD(mmHg)
+15.0 +13.0 +9.2 +5.5 +7.2 +9.6 +5.3 +2.2 +1.1 0.0 -7.6
Dapat dimodifikasi
Kegemukan Asupan garam berlebih Kurang bergerak/beraktivitas Stress Merokok
Proof of Benefit
1960s to 1980s several major clinical trials establish the facts that early treatment of hypertension would prevent complication and prolong life
VAS, USPHS, HDFP
Benefits of therapy :
Complications Control No. % Treated No. % % Improvement
563
342 140 79
9.0
5.4 2.2 1.2
417
252 76 46
6.6
4.1 1.2 0.7
27
24 50 42
Data from a subset of patients in VACS, USPHCS, HDFP, AustS, Oslo Study
Relative risk reduction of fatal events and combined fatal and nonfatal events in patients on active treatment versus placebo or no treatment
P
<0.01 <0.001 ns -13% -18% -1%
<0.02 <0.01 ns
- 30% - 23%
<0.001 <0.001
ESH-ESC 2003
BP Control Rates
Trends in awareness, treatment, and control of high blood pressure in adults ages 1874
National Health and Nutrition Examination Survey, Percent II 197680 51
Awareness
Treatment Control
31 10
II (Phase 1) 198891 73 55 29
II (Phase 2) 199194 68 54 27
19992000 70
59 34
Sources: Unpublished data for 19992000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC6.
England 6%
France 24%
India 9%
> 65 yr only
Goals of treatment
JNC VII ( 2003 ) :
@ < 140 / 90 mmHg or < 130 / 80 mmHg for those with Diabetes or Chronic Kidney disease. @ Achieve SBP goal especially in persons >50 years of age.
ESH ( 2003 ) :
@ At least below 140 / 90 mmHg ( lower values if tolerated ) @ Below 130 / 80 mmHg in Diabetics. @ Keeping in mind, however, that systolic below 140 mmHg may be difficult to achieved in elderly( more flexible )
Goals BP
BP Threshold & Target BP (mmHg) Low and medium risk >140/90 <140/90
High risk
DM
<160/90
<140/90
<130/<80
Number of antihypertensive agents Target BP (mmHg) 1 2 3 4 DBP <85 DBP <75 MAP <92 DBP <80 MAP <92 SBP <135/DBP <85
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure
Bakris GL, et al. Am J Kidney Dis 2000;36:646-661; Lewis EJ, et al. N Engl J Med 2001;345:851-860; Cushman WC, et al. J Clin Hypertens 2002;4:393-404
Not at BP goal
Full dose of single agent Switch to different agent at low dose Full dose of 2-drug combination Add a third drug at low dose
Not at BP goal
23 drug combination at full dose Full-dose single agent
Full doses of 23-drug combination
Task Force for ESHESC. J Hypertens 2007;25:110587
Step 2
Step 3
ACEI (or ARB*) + CCB + diuretic Add further diuretic therapy, -blocker, or -blocker. Consider seeking specialist advice
Step 4
Yes
2-AHDs combination for most (usually thiazide-type D and ACEI or ARB or BB or CCB
No BP intervention
No BP intervention
Lifestyle changes for several months, then drug treatment if preferred by the patient and resources available Lifestyle changes for several months, then drug treatment
Lifestyle changes
Lifestyle changes
Lifestyle changes
ESHESC Recommendations for Combining BP-lowering Drugs and Availability as Single-pill Combinations
Diuretics
-blockers
a-blockers
Tekanan darah diastolik (angka yang lebih rendah) lebih penting dari sistolik
FAKTA:
Tekanan darah sistolik dan diastolik samasama penting, bahkan pada usia lanjut, tekanan darah sistolik lebih harus dikontrol
Pada orang tua, sudah biasa tekanan darahnya tinggi, sehingga tidak perlu diobati (100 + umur mmHg adalah wajar)
FAKTA:
Baik orang muda maupun orang tua, tekanan darah HARUS di bawah 140/90 mmHg untuk mencegah komplikasi
Jika saya minum obat hipertensi dan tekanan darah saya terkontrol baik, obat tersebut tidak perlu diminum lagi
FAKTA:
Tekanan darah terkontrol tsb. karena disebabkan oleh obat. Jika obat dihentikan maka tensi akan meningkat kembali. Hipertensi tidak dapat disembuhkan, hanya dapat dikendalikan. Jadi obat hipertensi harus terus diminum sesuai instruksi dokter
Jika kita pusing-pusing dan leher terasa kaku, itu berarti tensi kita sedang naik. Jika tidak terasa apa-apa, tensi kita normal
FAKTA:
Hipertensi itu penyakit yang umumnya tidak bergejala. Untuk mengetahui apakah tensi kita naik atau tidak hanyalah mengukur dengan tensi meter. Periksalah tekanan darah secara teratur untuk mengetahui berapa tekanan darah kita.
Menunnggu sampai gejala dan tanda penyakit jantung koroner timbul baru diberi terapi sudah tidak benar . Pada beberapa keadaan, timbulnya atau telah adanya gejala justru menggambarkan kegagalan tindakan medis, bukan saat baru mulai terapi.
William B. Kannel, MD Department of Medicine Boston University Medical Center
Obat-obat anti-hipertensi
Bersikap sabar dalam menjalani pengobatan, tidak mengharapkan terapi yang ajaib yang cepat menurunkan tekanan darah Memberi kesempatan pada tubuh untuk menyesuaikan dengan obat yang mungkin memerlukan waktu untuk mengendalikan tekanan darah Obat diminum sesuai dengan anjuran dokter. Tidak menghentikan pengobatan sendiri atau merubah dosis dan segera mengunjungi dokter jika ditemukan adanya efek samping
Obat-obat anti-hipertensi
Diuretik Beta bloker Antagonis kalsium ACE inhibitor Alfa bloker Angiotensin II antagonis Central agonist dan vasodilator Anti Renin
Tolerability
1940s 1950
Direct vasodilators Peripheral sympatholytics Ganglion blockers Veratrum alkaloids
1957
1960s
1970s
1980s
1990s
ARBs
2005+
Renin Inh
ACE Alpha blockers inhibitors Thiazide diuretics Central alpha2 DHP CCBs agonists Non-DHP CCBs
The primary goal of treatment is to achieve maximum reduction in total CV risk, through treatment of Beta blockers elevated BP and all associated reversible risk factors DHP, dihydropyridine; CCB, calcium channel blocker; ARB, angiotensin II receptor blocker. ESH/ESC 2007
AMLODIPINE
Obat yang mempunyai masa kerja panjang dari generasi kedua antagonis kalsium Mempunyai waktu paruh 35-48 jam T/P Ratio >50% Dosis sekali sehari Menurunkan tekanan darah secara gradual
Pharmacokinetics: Olmesartan Olmesartan medoxomil is a prodrug, which is hydrolyzed to its active metabolite, olmesartan Absolute bioavailability 25.6% Time to Cmax ~2 hours t1/2 ~10-15 hours Dual elimination:
40% renal 60% hepatobiliary
Schwocho LR, et al. J Clin Pharmacol 2001;41:515-527; Laeis P, et al. J Hypertens 2001;19(Suppl 1):S21-S32
Pharmacokinetics: Summary (cont.) Not metabolized by cytochrome P450 system; interactions with drugs metabolized by CYP450 unlikely Can be administered with or without food No dosage adjustment necessary for the elderly or in patients with renal or hepatic impairment
BUT not recommended for patients with severe renal or hepatic impairment
Schwocho LR, et al. J Clin Pharmacol 2001;41:515-527; Laeis P, et al. J Hypertens 2001;19(Suppl 1):S21-S32; von Bergmann K, et al. J Hypertens 2001;19(Suppl 1):S33-S40
Olmesartan may give more prolonged AT1 blockade than irbesartan or valsartan
p vs placebo <0.0001 0.005 0.028 0.058 (NS) 0.002 0.004 0.036
p vs olmesartan
n=20
1.84
Valsartan 320 mg
Change in SeSBP
Losartan 50 mg/d Valsartan 80 mg/d
Olmesartan 20 mg/d
0 -2 Change in BP (mmHg)
-4
-6 -8
-10
-12 -14 -13.0
-8.9 **
-9.2 **
-10.8 *
* p0.05 ** p0.005
n=588
Results at Week 8
Change in SeDBP
Losartan 50 mg/d Valsartan 80 mg/d
n=588
Irbesartan 150 mg/d
Olmesartan 20 mg/d
Change in BP (mmHg)
-4
-8 -8.2 **
-7.9 ** -9.9 *
-11.5
40%
46%
16%
Oparil S, et al. J Clin Hypertens 2001;3:283-291; Brunner HR. J Hypertens 2003;21(Suppl 2):S43-S46
64 * 58 50 43
38
10
0 Diuretics Beta- blockers CCBs ACE inhibitors ARBs
ACE, angiotensin-converting enzyme; CCB, calcium-channel blocker; ARB, angiotensin II receptor blocker
ACEI + CCB
Less peripheral oedema Less cough Potentiation of the BP lowering effect Greater reduction of CV events Greater organ protection Antiinflamatory vasc effect Anti atherogenic properties Anti diabetogeniceffects Neutral effects on lipid profile and uric acid
Summary
Regardless of the blood pressure level, all patients should adopt appropriate lifestyle modifications A low dose of a diuretic should be considered as the first choice of therapy for the majority of patients without a compelling indication for another class of drug
2003 WHO/ISH Statement on Hypertension. J Hypertens 2003;21:1983-1992
Summary
Specific drug classes may differ in their effects Main benefits are due to BP lowering Drugs are not equal in adverse-event profiles Major drug classes are suitable for initiation and maintenance of therapy Choice of drug will be influenced by patient experience and preference, and cost and risk profile Long-acting drugs that provide once-daily, 24-hour efficacy are preferable
Thank You