In patients with HFrEF, canrenone was the most effective MRA for reducing heart failure hospitalization compared to placebo (HR 0.47; 95% CrI 0.21-0.92).
Meta-Analysis (n=32,329)
Do different mineralocorticoid receptor antagonists (MRAs) reduce mortality and hospitalizations in patients with heart failure with reduced ejection fraction?
In a Bayesian network meta-analysis of HFrEF patients, canrenone emerged as the most effective MRA for reducing heart failure hospitalizations, while spironolactone ranked highest for cardiovascular mortality reduction.
Hazard Ratio: 0.47 (95% CI 0.21–0.92)
Abstract Background Mineralocorticoid receptor antagonists (MRAs) play a vital role in managing heart failure with reduced ejection fraction (HFrEF) by reducing neurohormonal activation and improving clinical outcomes. While spironolactone and eplerenone have demonstrated benefits, newer MRAs such as finerenone and canrenone offer potential advantages. This Bayesian network meta-analysis (NMA) evaluates and ranks the effectiveness of MRAs in patients with HFrEF. Purpose To compare the effectiveness of different MRAs in HFrEF using a Bayesian network meta-analysis and to rank them based on their efficacy in reducing all-cause mortality, cardiovascular mortality, heart failure hospitalization, and hospitalization due to cardiovascular (CVS) causes. Methods A systematic search was performed in PubMed, Embase, and Scopus to identify RCTs evaluating the effectiveness of MRAs, compared to placebo in HFrEF patients. Hazard ratios (HR) with 95% credible intervals (CrI) were estimated for time-to-event outcomes compared to placebo. A random-effects Bayesian model was used, and Surface Under the Cumulative Ranking Curve (SUCRA) values were calculated to rank interventions. Bayesian inference was conducted using Markov Chain Monte Carlo (MCMC) simulations, with model convergence evaluated through the Gelman-Rubin diagnostic. Results We analyzed data from 32,329 patients across 16 RCTs. For hospitalization due to heart failure (HF), Canrenone was ranked as the most effective (HR: 0.47, 95% CrI: 0.21 to 0.92; SUCRA: 89.58%), followed by Finerenone (HR: 0.68, 95% CrI: 0.42 to 1.07; SUCRA: 59.56%) and Spironolactone (HR: 0.70, 95% CrI: 0.47 to 1.01; SUCRA: 56.26%), and Eplerenone (HR: 0.75, 95% CrI: 0.63 to 0.86; SUCRA: 42.48%), compared to Placebo (SUCRA: 2.12%). For hospitalization due to cardiovascular (CVS) causes, Canrenone was the most effective (HR: 0.53, 95% CrI: 0.25 to 0.98; SUCRA: 92.83%), followed by Spironolactone (HR: 0.75, 95% CrI: 0.52 to 0.94; SUCRA: 65.07%) and Eplerenone (HR: 0.86, 95% CrI: 0.73 to 1.01; SUCRA: 40.03%). For all-cause mortality, Canrenone had the lowest associated risk (HR: 0.56, 95% CrI: 0.17 to 1.30; SUCRA: 83.43%), followed by Spironolactone (HR: 0.71, 95% CrI: 0.57 to 0.88; SUCRA: 71.29%) and Eplerenone (HR: 0.81, 95% CrI: 0.72 to 0.95; SUCRA: 42.02%). For cardiovascular mortality, Spironolactone ranked the highest (HR: 0.65, 95% CrI: 0.21 to 1.40; SUCRA: 73.99%), followed by Finerenone (HR: 0.74, 95% CrI: 0.17 to 2.27; SUCRA: 70.24%) and Eplerenone (HR: 0.94, 95% CrI: 0.58 to 1.70; SUCRA: 37.35%). Conclusions This study suggests that Canrenone is the most effective for reducing hospitalization due to heart failure and cardiovascular causes, while Spironolactone and Finerenone also demonstrate significant benefits in reducing all-cause and cardiovascular mortality. These findings highlight the comparative efficacy of MRAs in HFrEF, emphasizing the need for further head-to-head trials to confirm these results.League table of HF hospitalization SUCRA plots showing intervention ranking
Khalil et al. (Sat,) conducted a meta-analysis in heart failure with reduced ejection fraction (HFrEF) (n=32,329). Mineralocorticoid receptor antagonists (Canrenone, Finerenone, Spironolactone, Eplerenone) vs. Placebo was evaluated on hospitalization due to heart failure (HF) (HR 0.47, 95% CI 0.21-0.92). In patients with HFrEF, canrenone was the most effective MRA for reducing heart failure hospitalization compared to placebo (HR 0.47; 95% CrI 0.21-0.92).