"Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both".
The New England Journal of Medicine. 2003. 349:1893-1906.PubMed•Full text•PDF

Contents

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 Outcome
8.2 Secondary Outcomes
9 Noninferiority
10 Tolerability and Safety
11 Discussion
12 Funding
13 Further Reading

Clinical Question

In high-risk patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both, how does the efficacy of valsartan, captopril, or the combination of both compare in terms of mortality?

Bottom Line

Valsartan is as effective as captopril for improving survival and reducing cardiovascular morbidity in high-risk patients following myocardial infarction. The combination of valsartan and captopril does not improve survival and increases the rate of adverse events.

Major Points

Guidelines

International guidelines recommend ACE inhibitors as first-line therapy for patients with myocardial infarction complicated by heart failure or left ventricular dysfunction.

Design

- Randomized, double-blind trial
- N=14,703
- Valsartan (n=4909)
- Valsartan plus captopril (n=4885)
- Captopril (n=4909)
- Median follow-up: 24.7 months

Population

Inclusion Criteria
- Age ≥18 years
- Acute myocardial infarction (0.5 to 10 days before)
- Complicated by heart failure, left ventricular systolic dysfunction (ejection fraction ≤0.35 or ≤0.40 depending on ventriculography method), or both

Exclusion Criteria
- Intolerance or contraindication to ACE inhibitors or angiotensin-receptor blockers
- Significant valvular disease or other severely limiting diseases

Baseline Characteristics
- Similar across all groups

Interventions

- Valsartan initiated at 20 mg, goal to reach 160 mg twice daily
- Valsartan + captopril initiated at combined doses, goal to reach valsartan 80 mg twice daily and captopril 50 mg three times daily
- Captopril initiated at 6.25 mg, goal to reach 50 mg three times daily

Outcomes

Primary Outcome
- Similar mortality rates across all groups

Secondary Outcomes
- Rates of secondary composite cardiovascular outcomes were similar across groups

Noninferiority
- Valsartan demonstrated noninferiority to captopril regarding mortality

Tolerability and Safety
- The combination group experienced the most drug-related adverse events
- With monotherapy, valsartan associated with more hypotension and renal dysfunction, while captopril associated with cough, rash, and taste disturbance

Discussion

Funding

Supported by a grant from Novartis Pharmaceuticals.

Further Reading

For additional information on this trial, read the full text available at: [NEJM URL].