Spironolactone is being evaluated in 730 patients with HFpEF/HFmrEF (median age 77.8 years, 52% women, 46.4% with recent HF hospitalization) for effects on HF hospitalizations and CV death.
RCT (n=730)
Double-blind
1:1
Sí
Does spironolactone reduce the rate of total HF hospitalizations and cardiovascular death in patients aged ≥50 years with HFpEF/HFmrEF?
The SPIRIT-HF trial enrolled 730 high-risk patients with HFpEF/HFmrEF to evaluate the efficacy of spironolactone on total HF hospitalizations and cardiovascular death.
Abstract Aims This report describes the design and baseline characteristics of the SPIRIT-HF trial and compares them with prior heart failure with mildly reduced or preserved ejection fraction (HFpEF/HFmrEF) trials. Methods and Results In this multicenter, double-blind, placebo-controlled phase III trial, 730 patients aged ≥50 years with left ventricular ejection fraction (LVEF) ≥40%, New York Heart Association (NYHA) class II-IV symptoms, and either elevated N-terminal-pro-B-type natriuretic peptide (NT-proBNP) or HF hospitalization within 12 months were randomized 1:1 to spironolactone or placebo. The primary endpoint is a composite of rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months from randomization, which will be analyzed using the LWYY model. Secondary endpoints in a hierarchical order include total HF hospitalizations, CV hospitalizations, all hospitalizations, and cardiovascular death within 24 months from randomization. Results will first be analyzed based on the SPIRIT-HF dataset only. Then, a pre-specified individual participant data meta-analysis combining SPIRIT-HF and TOPCAT Americas will be conducted to refine treatment effect estimates. The median age of the patients enrolled in the SPIRIT-HF was 77.8 years, and 52% were women. The median LVEF was 55% (50-60), with 18% of patients having a LVEF between 40-49%. In SPIRIT-HF, prior HF hospitalization was similarly frequent (46.4% vs. 55%), but NT-proBNP was slightly higher (970 vs. 900 pg/ml) compared to TOPCAT Americas. However, the proportion of patients with NYHA class III (33% vs. 35%), patients with comorbidities such as atrial fibrillation at baseline electrocardiogram (25% vs. 25%) and chronic kidney disease (50% vs. 48%); and background therapy, such as beta-blockers (76% vs. 79%), and diuretics (83% vs. 89%), including loop diuretics (69% vs. 78%), were similar between SPIRIT-HF and TOPCAT Americas. Compared with prior HFpEF/HFmrEF trials, SPIRIT-HF patients demonstrated a higher risk with a similar proportion of patients with recent HF hospitalization (46.4%) and slightly higher NT-proBNP concentrations (970 pg/ml) at baseline. Conclusion SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.
Zurkan et al. (Mon,) conducted a rct in Heart failure with mildly reduced or preserved ejection fraction (HFpEF/HFmrEF) (n=730). Spironolactone vs. Placebo was evaluated on Composite of rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months from randomization. Spironolactone is being evaluated in 730 patients with HFpEF/HFmrEF (median age 77.8 years, 52% women, 46.4% with recent HF hospitalization) for effects on HF hospitalizations and CV death.