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"Captopril in Patients with Left Ventricular Dysfunction After Myocardial Infarction". The New England Journal of Medicine. 1992. 327(10):669-677. PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with left ventricular dysfunction but not overt heart failure following myocardial infarction (MI), does treatment with the ACE inhibitor captopril reduce morbidity and mortality?

Bottom Line

In patients with left ventricular dysfunction after MI, long-term administration of captopril was associated with improved survival, reduced cardiovascular mortality, fewer major cardiovascular events, and attenuated ventricular remodeling.

Major Points

The study randomized 2231 patients to either captopril or placebo. Patients had an ejection fraction (EF) ≤40% and were within 3 to 16 days post-MI, without symptoms of ongoing ischemia or manifest heart failure. The results over the mean 42-month follow-up showed a 19% reduction in all-cause mortality and significant reductions in cardiovascular mortality and morbidity in the captopril group compared to placebo.

Guidelines

Current guidelines recommend ACE inhibitors in patients with systolic dysfunction, both symptomatic and asymptomatic, following MI to improve survival.

Design

- Multicenter, double-blind, placebo-controlled randomized clinical trial
- N=2,231
- Captopril: 1,115
- Placebo: 1,116
- Setting: 112 hospitals in the United States and Canada
- Enrollment: January 1987 - January 1990
- Follow-up: Average of 42 months
- Analysis: Intention-to-treat
- Primary outcome: All-cause mortality

Population

Inclusion Criteria
- Survived the first 3 days post-MI
- Left ventricular ejection fraction ≤40%
- Age ≥21 and <80

Exclusion Criteria
- Contraindication to ACE inhibitor use
- Need for an ACE inhibitor for other indications (heart failure, hypertension)
- Serum creatinine >2.5 mg/dL
- Unstable post-MI course
- Inability to consent or comply with follow-up

Baseline Characteristics
- No significant differences between groups at baseline.

Interventions

- Captopril: Initial dose of 12.5 mg (or 6.25 mg in select cases) with a target of 25 mg three times daily by end of hospital phase, and up to 50 mg three times daily as tolerated.
- Placebo: Administered following the same schedule as captopril.

Outcomes

Primary Outcomes
- 19% reduction in all-cause mortality (captopril group 20% vs. placebo group 25%; P=0.019)

Secondary Outcomes
- 21% reduction in cardiovascular mortality (P=0.014)
- 37% reduction in development of severe heart failure (P<0.001)
- 22% reduction in congestive heart failure requiring hospitalization (P=0.019)
- 25% reduction in recurrent myocardial infarction (P=0.015)
- Less deterioration in ejection fraction (captopril group 13% vs. placebo group 16%; P=0.168)

Criticisms

- The potential impact of newer treatments and strategies for MI developed after the study period is not assessed.

Funding

The trial was supported by a grant from the Bristol-Myers Squibb Institute for Pharmaceutical Research, which had no role in data management or unblinded information access.