ACE Inhibitors :

The Foundation of RAAS Blocker

in Combination Therapy

Presented by: Hendro Darmawan

1 November 2014

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%

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)

Hypertension causes end-organ damage

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

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.

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

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

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.”

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)

“Ask a simple & clinically relevant question”“Answer it reliably”

What to choose ?

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

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.

Both act on the renin-angiotensin system

But,,,

different pharmacology and mode of action

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

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.

Different Evidence based among RAAS-I

Perindopril: The most proven ACE-I

PERINDOPRIL

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

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

Perindopril provides better CV protection

Perindopril

Can we go further to protect our hypertension patients ?

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.

Thank You