Spironolactone in the Treatment of Heart Failure with Mildly Reduced or Preserved Ejection Fraction: Design and Baseline Characteristics of the SPIRIT-HF-DZHK08 Trial.
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.
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.
SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.
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.
SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.
Authors
Zurkan Zurkan, Pieske Pieske, Petutschnigg Petutschnigg, Verheyen Verheyen, Khan Khan, Ferreira Ferreira, Girerd Girerd, Biegus Biegus, Felix Felix, Hasenfuß Hasenfuß, Mosterd Mosterd, Pitt Pitt, Ponikowski Ponikowski, Shah Shah, Trippel Trippel, Zannad Zannad, Placzek Placzek, Friede Friede, Anker Anker, Edelmann Edelmann
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