RALES
Trial question
What is the role of spironolactone in patients with severe HF and a LVEF < 35% who were being treated with ACEi?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
27.0% female
73.0% male
N = 1663
1663 patients (446 female, 1217 male).
Inclusion criteria: patients with severe HF and an LVEF < 35% who were being treated with ACEi.
Key exclusion criteria: congenital heart disease, unstable angina, primary hepatic failure, active cancer, or any life-threatening disease (other than HF), or heart transplantation.
Interventions
N=822 spironolactone (25 mg daily).
N=841 placebo (matching placebo daily).
Primary outcome
Death at 24 months
35%
46%
46.0 %
34.5 %
23.0 %
11.5 %
0.0 %
Spironolactone
Placebo
Significant
decrease ▼
NNT = 9
Significant decrease in death at 24 months (35% vs. 46%; RR 0.7, 95% CI 0.6 to 0.82).
Secondary outcomes
Significant decrease in frequency of hospitalization for worsening HF (26% vs. 35%; RR 0.65, 95% CI 0.54 to 0.77).
Significant increase in gynecomastia or breast pain (10% vs. 1%; RR 10, 95% CI 4.07 to 15.93).
Safety outcomes
No significant difference in serious hyperkalemia.
Significant differences in gynecomastia or breast pain (10% vs. 1%, p < 0.001).
Conclusion
In patients with severe HF and an LVEF < 35% who were being treated with ACEi, spironolactone was superior to placebo with respect to death at 24 months.
Reference
Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17.
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