Authors
The CONSENSUS Trial Study Group
Title
Effects of enalapril on mortality in severe congestive heart failure
References
N Engl J Med 1987;316:1429-35
Background
At the time of the initiation of the study, the impact of ACE inhibitors on survival in patients with HF is not yet known.
Purpose
To determine if the addition of enalapril to standard heart failure treatment (digitalis and diuretics) improves clinical outcomes in patients with severe HF (NYHA Class IV).
Design
Randomized, double-blind, placebo-controlled trial 253 patients with NYHA class IV symptoms (mean age of 70 years) and a heart size >600 mL/m² in men and >550 mL/m² in women Receiving conventional HF treatment, including digitalis, diuretic and vasodilators
Exclusion Criteria
acute pulmonary edema, MI within previous two months, UA, hemodynamically important aortic or mitral valve stenosis, planned cardiac surgery, right heart failure due to pulmonary disease or serum creatinine >300 µmol/L
Follow-Up
Average of 188 days (range from 1 day to 20 months). Trial discontinued early due to survival benefits with enalapril.
Treatment Regimen
Enalapril 5 mg PO twice daily x 1 week, then 10 mg twice daily, then target dose of 20 mg twice daily (dose titrated in the absence of hypotension and other side effects) high risk hypotension patients (serum sodium <130 mmol/L, serum creatinine 150-300 µmol/L, an increase in diuretic doses within the previous week, treatment with potassium sparing agents) were initiated on enalapril 2.5 mg once daily and titrated to target dose patients were evaluated at 1, 2, 3, 6, and 16 weeks, 6, 9, and 12 months and at the end of the study additional vasodilators were recommended for patients with worsening symptoms in the orders of isosorbide dinitrate, hydralazine or prazosin
Results
Primary Endpoints Death at 6 months: 26% (enalapril) vs. 44% (placebo); RRR 40%, p=0.002. Causes of death: Progression of congestive heart failure: 50% reduction with enalapril compared to placebo, p=0.001 Sudden cardiac death: no difference in the incidence between the two groups, p>0.25 Soncondary Endpoints (see study for complete list) Death at 12 months: 36% (enalapril) vs. 52% (placebo); RRR 31%, p=0.001. Total death: 39% (enalapril) vs. 54% (placebo); RRR 0.73, p=0.003. NYHA Classification improvement: 42% (enalapril) vs. 22% (placebo); p<0.001
Summary
When added to the then standard therapy for patients with severe HF, enalapril improves symptoms and improves survival rates by specifically reducing death from worsening heart failure as compared to placebo.