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"Enalapril in Severe Congestive Heart Failure". The New England Journal of Medicine. 1987. 316(23):1429-1435. PubMed

Links to original sources: Wiki Journal Post Full Journal Article

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 Criticisms 10 Funding 11 Further Reading

Clinical Question


Does the addition of the angiotensin-converting-enzyme inhibitor enalapril to conventional therapy in patients with severe congestive heart failure improve survival and symptoms?

Bottom Line


In patients with severe congestive heart failure (NYHA class IV), enalapril reduces mortality and improves symptoms when added to conventional therapy.

Major Points


The prognosis of severe congestive heart failure is poor, but the utility of angiotensin-converting-enzyme inhibitors (ACE inhibitors) on survival was previously unknown. This landmark randomized controlled trial established that enalapril significantly improved both survival and clinical symptoms in patients with severe heart failure.

Guidelines


Modern guidelines recommend ACE inhibitors as part of standard therapy for heart failure with reduced ejection fraction.

Design


- Multicenter, double-blind, placebo-controlled, parallel-group trial - N=253 patients with NYHA class IV heart failure - Enalapril (n=127) - Placebo (n=126) - Follow-up averaged 188 days, up to 20 months - Primary endpoint: Crude mortality at six months - Secondary endpoints: 12-month and overall mortality during the entire trial period

Population


Inclusion Criteria

- Severe congestive heart failure (NYHA class IV) - History of heart disease with symptoms of dyspnea or fatigue or both, along with signs of fluid retention and no evidence of primary pulmonary disease - Enlarged heart size radiologically (more than 600 ml/m² in men or more than 550 ml/m² in women)

Exclusion Criteria

- Acute pulmonary edema, significant valve stenosis, recent myocardial infarction, unstable angina, planned cardiac surgery, right heart failure due to pulmonary disease, serum creatinine above 300 μmol/L

Baseline Characteristics

- Similar clinical characteristics between enalapril and placebo groups

Interventions


- Enalapril or placebo started with a dose of 5 mg twice a day in the hospital, increased to 10 mg twice daily after one week as tolerated, and further increased up to 20 mg twice a day - Protocol adjusted for high-risk patients to start at 2.5 mg daily

Outcomes


Primary Outcome

- Six-month mortality was 26% in the enalapril group vs. 44% in the placebo group

Outcomes


- Mortality at one year and end of the study was reduced by 31% and 27%, respectively, with enalapril - Sudden cardiac death incidence was similar between groups - Deaths from progression of heart failure reduced by 50% in enalapril group

Criticisms


- The trial's dosage and administration adjustments may not reflect current practice - The study did not provide long-term data on the duration of the beneficial effect or its effects in less severe forms of heart failure

Funding


- Supported by a grant from Merck Sharp and Dohme Research Laboratories

Further Reading


More detail can be found in the original publication in The New England Journal of Medicine.