"Spironolactone for Severe Heart Failure".The New England Journal of Medicine. 1999. 341(10):709-717.
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Contents 1Clinical Question 2Bottom Line 3Major Points 4Guidelines 5Design 6Population 6.1Inclusion Criteria 6.2Exclusion Criteria 6.3Baseline Characteristics 7Interventions 8Outcomes 8.1Primary Outcome 8.2Secondary Outcomes 9Criticisms 10Funding 11Further Reading
In patients with severe heart failure and a left ventricular ejection fraction of 35% or less being treated with an ACE inhibitor, does the addition of spironolactone reduce mortality and morbidity?
In patients with severe heart failure and a left ventricular ejection fraction of no more than 35%, addition of spironolactone to standard therapy including an ACE inhibitor significantly reduces mortality and hospitalization for cardiac reasons, improves symptoms, and is well-tolerated.
Aldosterone has a key role in the progression of heart failure, and standard therapy with an ACE inhibitor may not adequately suppress aldosterone production. Previous research indicated that low doses of spironolactone, an aldosterone-receptor antagonist, in conjunction with standard heart failure treatment, might be effective and safe without leading to serious hyperkalemia.
At the time of this study's publication, guidelines did not reflect the study's findings and would presumably be updated to accommodate the new evidence on spironolactone's effect on heart failure management.
- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial - N=1,663 patients with recent severe heart failure - Spironolactone (n=822) - Placebo (n=841) - Mean follow-up: 24 months - Analysis: Intention-to-treat
Inclusion Criteria - NYHA class IV heart failure within six months before enrollment - NYHA class III or IV at the time of enrollment - Diagnosis of heart failure at least six weeks before enrollment - Treatment with an ACE inhibitor and loop diuretic - Left ventricular ejection fraction of no more than 35%
Exclusion Criteria - Primary operable valvular heart disease, congenital heart disease - Unstable angina, primary hepatic failure, active cancer - Waitlisted or undergone heart transplantation - Serum creatinine >2.5 mg/dL, serum potassium >5.0 mmol/L
Baseline Characteristics - Balanced characteristics between placebo and treatment groups
- Patients were randomized to receive 25 mg of spironolactone daily or matching placebo.
Primary Outcome - All-cause mortality: 35% reduction in the spironolactone group compared to placebo (relative risk 0.70; P<0.001).
- Cardiac mortality and hospitalization for cardiac reasons were significantly reduced in the spironolactone group. - Improvement in symptoms based on NYHA functional class (P<0.001).
- The long-term safety and efficacy of spironolactone in a broader range of heart failure patients or in those at lower risk were not assessed in this study.
- Supported by a grant from Searle (manufacturer of spironolactone).
- The preliminary data from this study were presented at the AHA meeting in Dallas, November 8–11, 1998.