Cardiovascular Benefits of Finerenone Beyond Renal Protection: A Meta-Analysis of Renal and Cardiovascular Phase 3 Randomized Trials

Background Mineralocorticoid receptor (MR) overactivation promotes inflammation, fibrosis, and adverse cardiac remodelling, contributing to the progression of heart failure and cardiovascular disease. Finerenone is a non-steroidal MR antagonist characterized by high MR selectivity, balanced heart–kidney tissue distribution, and a favourable safety profile. Although phase 3 trials have shown cardiovascular benefit, it remains uncertain whether these effects reflect direct cardio-protection or are predominantly mediated through renal mechanisms. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials comparing finerenone with placebo or standard therapy. PubMed, Embase, and Cochrane CENTRAL were searched through December 31, 2025. Outcomes included a composite cardiovascular endpoint, heart failure hospitalization (HFH), and cardiovascular (CV) death. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using random-effects models. Treatment effects were compared between renal-focused trials and a dedicated cardiovascular trial, with exploratory meta-regression analyses. Results Four phase 3 trials including 19,827 patients were analysed. Finerenone significantly reduced the composite cardiovascular endpoint (OR 0.81, 95% CI 0.74–0.89) and HFH (OR 0.76, 95% CI 0.69–0.83), with low heterogeneity and consistent effects across trial populations. A non-significant trend toward reduced CV death was observed (OR 0.89, 95% CI 0.79–1.00). No effect modification by trial type or baseline characteristics was detected. Conclusions The consistency of heart failure risk reduction across renal and cardiovascular trial settings supports a direct cardioprotective effect of finerenone, likely mediated through attenuation of MR-driven inflammation and fibrosis, rather than a purely renal-dependent mechanism.