Finerenone, polypharmacy, and clinical outcomes in heart failure: pre-specified analysis from the FINEARTS-HF trial

AIMS: Patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high comorbidity burden, which may necessitate numerous medications. Patients and clinicians may be hesitant about initiating another medication, especially among those already experiencing polypharmacy. This pre-specified analysis sought to examine the efficacy and safety of adding finerenone based on the concomitant medication number. METHODS: In the FINEARTS-HF trial, baseline medication use was collected in all 6001 participants with HFmrEF/HFpEF. Clinical outcomes and treatment effects were assessed by the categories of total medication count ('non-polypharmacy': ≤4 medications; 'polypharmacy': 5-9 medications; and 'hyper-polypharmacy': ≥10 medications) and as continuous variables. The primary outcome was a composite of cardiovascular death and total HF events. RESULTS: Overall (age: 72 ± 10 years; 46% women), the total number of medications at baseline ranged from 0 to 29 (mean: 8.4 ± 3.6), with 3588 (60%) meeting polypharmacy and 1878 (31%) meeting hyper-polypharmacy. Incidence rates for the primary outcome increased across medication categories: non-polypharmacy, 10.2; polypharmacy, 12.3; and hyper-polypharmacy, 26.1 per 100 person-years. The treatment benefits of finerenone in reducing the primary outcome were consistent across the spectrum of total medication count (Pinteraction = 0.94). Any serious adverse events and study drug discontinuation were not more frequent with finerenone vs placebo, regardless of polypharmacy categories. CONCLUSION: In FINEARTS-HF, >90% of patients with HFmrEF/HFpEF met the criteria for polypharmacy or hyper-polypharmacy, and these patients faced excess risks of cardiovascular events. Finerenone safely reduced cardiovascular death and total HF events across a broad range of baseline medication use.