- Question
- Does adding an aldosterone-receptor blocker (spironolactone) to standard therapy reduce morbidity and mortality in patients with severe heart failure?
- Design
- Randomized, double-blind, placebo-controlled trial of 1663 patients. It was stopped early after a mean follow-up of 24 months because an interim analysis showed spironolactone was efficacious.
- Population
- Patients with severe heart failure and a left ventricular ejection fraction of 35% or less, treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic and, in most cases, digoxin.
- Intervention
- Spironolactone 25 mg daily added to standard therapy (822 patients).
- Control
- Placebo added to standard therapy (841 patients).
- Primary outcome
- Death from all causes.
- Results
- There were 386 deaths in the placebo group (46%) and 284 in the spironolactone group (35%); relative risk of death 0.70 (95% CI 0.60 to 0.82; P<0.001). Hospitalization for worsening heart failure was 35% less frequent with spironolactone (relative risk 0.65; 95% CI 0.54 to 0.77; P<0.001).
- Safety
- Gynecomastia or breast pain occurred in 10% of men treated with spironolactone versus 1% with placebo (P<0.001). The incidence of serious hyperkalemia was minimal in both groups.
- Conclusion
- Aldosterone-receptor blockade with spironolactone on top of standard therapy substantially reduces morbidity and mortality in severe heart failure.
- Why it matters
- It established aldosterone antagonists as an additional cornerstone of treatment for heart failure with reduced ejection fraction, beyond ACE inhibitors.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 7, 2026