Efficacy and Tolerability of Finerenone According to the Use and Dosage of Diuretics

Importance Given their kidney actions, it is important to evaluate the efficacy and safety of mineralocorticoid receptor antagonists when combined with other diuretics and whether they have a so-called diuretic-sparing effect in patients with heart failure (HF). Objective To examine the efficacy and tolerability of finerenone related to background diuretic treatment in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Design, Setting, and Participants This study is a prespecified secondary analysis of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) randomized clinical trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with HFmrEF/HFpEF, who were randomized between September 2020 and January 2023. Data analysis was conducted from December 1, 2024, to January 30, 2025. Intervention Finerenone (titrated to 20 mg or 40 mg) or placebo. Main Outcomes and Measures The primary outcome was the composite of total HF events and cardiovascular death. Outcomes were compared between finerenone and placebo according to the following baseline diuretic categories: only a nonloop diuretic (thiazide or thiazide-like); loop diuretic (≤40 mg vs >40 mg furosemide-equivalent dose); and combined nonloop and loop diuretic use. Results Among 5438 patients, 2496 (45.9%) were female, and mean (SD) age was 72.1 (9.6) years. A total of 684 patients (12.6%) were receiving a nonloop diuretic, 3040 (55.9%) less than or equal to 40 mg furosemide equivalent, 1145 (21.1%) 40 mg or greater furosemide equivalent, and 569 (10.5%) both nonloop and loop diuretics. Compared with placebo, finerenone reduced the risk of the primary end point across all diuretic subgroups: rate ratios were 0.84 (95% CI, 0.47-1.51), 0.86 (95% CI, 0.72-1.02), 0.98 (95% CI, 0.78-1.24), and 0.54 (95% CI, 0.35-0.83) for patients in the nonloop, 40 mg or less loop, more than 40 mg loop, and combined nonloop and loop categories, respectively ( P for interaction = .18). Compared with placebo, finerenone reduced loop diuretic dose and dose intensification, but not loop diuretic initiation. Safety was consistent across diuretic categories. Conclusions and Relevance In this secondary analysis of the FINEARTS-HF randomized clinical trial, the efficacy and safety of finerenone were consistent across all diuretic subgroups. Compared with placebo, finerenone reduced the use of diuretics in patients with HFmrEF/HFpEF; however, finerenone did not reduce the initiation of new loop diuretic in participants not receiving a loop diuretic at baseline. Trial Registration ClinicalTrials.gov Identifier: NCT04435626