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ACE Inhibitors :
The Foundation of RAAS Blocker
in Combination Therapy
Presented by: Hendro Darmawan
1 November 2014
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Projected Increases in
Worldwide Hypertension prevalence
Kearney et al. Lancet. 2005; 365(9455):217-23.
Prevalensi Hipertensi RISKESDAS (2007) 31,7% RISKESDAS (2013) 25.8%
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37 % Indonesian people not treated
not treated
37%
treated
63%
Setiati S, Sutrisna S. Acta Med.Indones,2005 Jan-Mar;37(1):20-5
N=1814
Adult population over 40 years and above
Telah mendapat terapi atau minum obat antihipertensi 24.2 %
Yang terkontrol 18 %
Yang belum terjangkau pelayanan kesehatan 75.8 % (RISKESDAS 2013)
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Hypertension causes end-organ damage
Chobanian AV, et al. JAMA. 2003;289:2560-2572
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6
Initial Drug Therapy
BP
Classification
SBP*
(mm
Hg)
DBP*
(mm
Hg)
Lifestyle
Modification
Without
Compelling
Indications
With
Compelling
Indications
Normal <120 and <80 Encourage
No antihypertensive
drug indicated.
Drug(s) for
compelling
indications.Prehypertension 120–139 or 80–89 Yes
Stage 1
hypertension140–159 or 90–99 Yes
Thiazide-type diuretic
for most. May consider
ACEI, ARB, BB, CCB,
or combination.
Drug(s) for
compelling
indications.
Other
antihypertensive drugs
(diuretic, ACEI, ARB,
BB, CCB) as needed.
Stage 2
hypertension160 or 100 Yes
Two-drug combination
for most (usually
thiazide-type diuretic
and ACEI or ARB or
BB or CCB).
JNC 7: Classification and Management
of Blood Pressure for Adults
JNC 7. May 2003. NIH publication 03-5233.
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JNC-VII. Hypertension. 2003.
ACE inhibitors are recommended in a wide majority of patients – JNC 7 Guideline
Heart failure
Post myocardial
infarction
High coronary
disease risk
Diabetes
Chronic kidney
disease
Recurrent stroke
prevention
Diuretic Clinical trial basis-blocker ACEI ARB CCB Aldo ANT
Recommended Drugs
ACC/AHA Heart Failure
Guideline, MERIT-HF,
COPERNICUS, CIBIS, SOLVD,
AIRE, TRACE, ValHEFT, RALES,
CHARM
ACC/AHA Post-MI Guideline,
BHAT, SAVE, Capricorn,
EPHESUS
ALLHAT, HOPE, ANBP2, LIFE,
CONVINCE, EUROPA, INVEST
NKF-ADA Guideline, UKPDS,
ALLHAT
NKF Guideline, Captopril Trial,
RENAAL, IDNT, REIN, AASK,
PROGRESS
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What makes a good BP control pill?
Recommended by international
guideline
Get patients to goal
Provides 24 hour control
Has good tolerability
Has ‘added’ protection
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Hypertension Guidelines: an ultimate goal
Goals of treatment
“The primary goal of treatment of the hypertensive patient is
to achieve the maximum reduction in the long-term total risk
of cardiovascular morbidity and mortality.”
Therapeutic Management of Hypertension
“Antihypertensive treatment translates into significant
reductions of cardiovascular morbidity while having a
less significant effect on all cause mortality.”
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Bakris et al. Am J Kidney Dis. 2000;36:646-661; Bakris et al. Arch Intern Med. 2003;163:1555-1565; Lewis et al. N Engl J Med. 2001;345:851-860.
Number of BP Medications
Combination is needed to Achieve BP Goal
UKPDS (<85 mm Hg, diastolic)
4321
MDRD (<92 mm Hg, MAP)
HOT (<80 mm Hg, diastolic)
AASK (<92 mm Hg, MAP)
RENAAL (<140/90 mm Hg)
IDNT (135/85 mm Hg)
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“Ask a simple & clinically relevant question”“Answer it reliably”
What to choose ?
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Controls blood pressure
In hypertension:
newly diagnosed
or uncontrolled
with previous
therapy
Julius S, Cohn J, Neutel J, et al. Antihypertensive utility of perindopril in a large, general practice based clinical trial. J Clin Hypertens. 2004;6:10-17.
PERINDOPRIL
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Evidence versus conventional opinion
is the vision of a mean effect adapted
to the antihypertensive treatment?
Antihypertensive drugs are so different.
Even in the same drug class, there are huge
differences in terms of duration of action and
dosage.
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Both act on the renin-angiotensin system
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But,,,
different pharmacology and mode of action
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No class effect, but why ?
Different tissue affinity
Different effects on bradykinin (anti-
apoptoic) and angiotensin (proapoptoic)
Specific effects on typical apoptoic
inducer: TNF-α
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Different Effect even from same class inhibition
1. Ferrari R. Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. Expert Rev Cardiovasc Ther. 2005;3:15-29. 2. Ceconi C, Francolini G, Olivares A, et al.
Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol. 2007;577:1-6.
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Different Evidence based among RAAS-I
Perindopril: The most proven ACE-I
PERINDOPRIL
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Perindopril reduce cardiac and renal
events in diabetic patients
Per+Ind, perindopril+indapamide fixed combination†Non-fatal MI or death from coronary heart disease‡Unstable angina requiring hospitalisation, coronary revascularisation or silent MI
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Perindopril: Real BP Control (24-h BP Control)
1. Physicians’ Desk Reference. 55th ed. Montvale, NJ: Medical Economics Company; 2001. 2. Morgan T. Br J Cardiol. 1995;(suppl 1):57-59.
PERINDOPRIL
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Perindopril provides better CV protection
Perindopril
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Can we go further to protect our hypertension patients ?
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Conclusion
Not all antihypertensive (RAAS-I) is the same.
The right choice of antihypertensive will help doctor to
prevent target organ damage caused by hypertension.
Perindopril is the most proven ACE-I that is effective in
monotherapy and should be chosen as based in
combination therapy.
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Thank You