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.
D. Zurkan, B. Pieske, J. Petutschnigg et al.· European Journal of Heart Fa...· 1 citation
BACKGROUND AND AIM
Randomized trials conducted in the early 2000s established the survival benefit of primary prevention implantable cardioverter-defibrillator (ICD) therapy in patients with reduced left ventricular ejection fraction (LVEF) after myocardial infarction. However, management of myocardial infarction and heart failure has substantially evolved since that time. We investigated whether the estimated association between primary prevention ICD implantation in post-myocardial infarction patients with reduced LVEF and mortality reduction has changed over time.
METHODS
We analyzed individual participant data from 32,214 patients with LVEF ≤35% after myocardial infarction included in the PROFID pooled cohort, comprising 7,477 patients carrying a primary prevention ICD (ICD patients) and 24,737 patients without an ICD (non-ICD patients). The primary endpoint was all-cause mortality. Propensity scores were estimated using multivariable logistic regression including age, sex, LVEF, renal function, and diabetes, and overlap weighting was applied to balance treatment groups. Time period-specific analyses were performed across three prespecified time periods defined by inclusion year: 1995-2004, 2005-2014, and 2015-2020. Weighted cumulative mortality curves were generated for each time period. Temporal changes in the estimated association between ICD implantation and mortality reduction were assessed using a weighted Cox proportional hazards model.
RESULTS
A total of 12,097 deaths occurred during a mean follow-up of 43.7 months. The estimated association between ICD implantation and mortality changed significantly across time (P for interaction <0.001). In weighted time period-specific analyses, the estimated mortality reduction associated with ICD implantation progressively decreased over more recent periods. The hazard ratio for ICD versus non-ICD patients was 0.54 (95% CI 0.47-0.62; P<0.001) in 1995-2004, 0.67 (95% CI 0.62-0.72; P<0.001) in 2005-2014, and 0.89 (95% CI 0.73-1.07; P=0.221) in 2015-2020, with negligible separation of the weighted cumulative mortality curves in the most recent time period.
CONCLUSIONS
In this analysis including a large cohort of post-myocardial infarction patients with reduced LVEF, the estimated mortality reduction associated with primary prevention ICD implantation progressively decreased over time.
A. Sepehri Shamloo, T. Chiba, J. G. Tijssen et al.· European Heart Journal· 0 citations
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