HEART FAILURE BENEFITS FROM ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS

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HEART FAILURE BENEFITS FROM ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS

Clinical Bottom Lines:

ACE inhibition is first line therapy for the entire spectrum of CHF, whether asymptomatic or severe.

Drug therapy in most trials was titrated to captopril 50mg tid or enalapril 20 mg od as BP tolerated.

ACE inhibition should be started 72 h after any acute MI with symptoms or echocardiographic evidence of systolic dysfunction[5].

It is unclear if digoxin will have an additive therapeutic effect to ACE-I in patients in sinus rhythm.

Concomitant use of diuretics may be necessary.

ACE inhibition should not be started within the first 24 h of an acute MI.

Consider Isosorbide Dinitrate/Hydralazine if ACE inhibition is not tolerated[9].

Appraiser: HN Lee, October 5th 1992

The Evidence:

Trial/Study

Control

RRR

ARR

NNT

CONSENSUS¹: NYHA Class IV

Mortality (1 yr)

placebo

.52

enalapril

.36

.31

.16

V-HeFT II² : NYHA Class II-III

(2 year mortality)

ISDN / Hyd

.38

enalapril

.33

.14

.05

SOLVD I³: NYHA II - III

(1 year mortality)

(3 year mortality)

placebo

.16

.40

enalapril

.12

.35

.25

.16

.04

.05

Munich M.H.F¹⁰: NYHA I-III

(3 yr progression to class IV)

(Approx 3 yr mortality)

placebo

.27

.25

captopril

.11

.26

.59

-.05

.16

-.01

n/a

SOLVD II⁴: NYHA I/II

Heart failure

Rehospitalization

3 year mortality

placebo

.30

.05

.16

enalapril

.21

.03

.15

.37

.40

.06

.09

.02

.01

100

SAVE⁵: NYHA I post MI (3-16)d

CHF hospitalization

Recurrent MI

3.5 year mortality

placebo

.17

.15

.25

captopril

.14

.12

.20

.18

.20

.19

.03

.05

Comments:

1. There are also published meta-analyses on ACE inhibition therapy⁶ and digoxin use in CHF patients who

remain in sinus rhythm⁷. Basically, they support the conclusions listed above.

2. ACE-inhibition has additive therapeutic efficacy over aspirin and thrombolytics post MI.

3. The results of CONSENSUS II⁸ do not support the use of IV enalapril within the 1st 24h of an MI.

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REFERENCES:

[1] CONSENSUS. NEJM 1987;316:1429-1435.

[2] VeHeft II. NEJM 1991; 325(5):303-310.

[3] SOLVD I. NEJM 1991; 325(5):293-302.

[4] SOLVD II. NEJM 1992; 327(10):685-691.

[5] SAVE. NEJM 1992; 327(10):669-677.

[6] Mulrow CD et al. Meta analysis of RCT's of vasodilator therapy in CHF. JAMA 1988;(259):3422-3426.

[7] Jaeschke et al. Meta analysis of RCT's of digoxin therapy of CHF and sinus rhythm. American J Med 1990;88:279-286. (Most of the RCT's were of pre-ACE inhibition era).

[8] CONSENSUS II. NEJM 1992; 327(10)678-685.

[9] V-Heft I. NEJM 1986;314;(24):1547-1552.

[10] Munich Mild Heart Failure Trial. Br Heart J 1992(67):289-296.

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