6/29/23, 12:43 AM RALES Pathway Feedback Search Clinical Topics Home Studies RALES RALES Disease Heart failure 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 N = 1663 73.0% male 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 https://web.pathway.md/studies/rec1TTi3U6insNBVH 1/2 6/29/23, 12:43 AM RALES Pathway 46.0 % 46 35 34.5 % 23.0 % Significant decrease 11.5 % NNT = 9 0.0 % Spironolactone Placebo 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. Open reference URL https://web.pathway.md/studies/rec1TTi3U6insNBVH 2/2