Finerenone and polypharmacy in heart failure with mildly reduced or preserved ejection fraction: a marker of risk, not a barrier to therapy

This Editorial Comment refers to ‘Finerenone, polypharmacy, and clinical outcomes in heart failure: pre-specified analysis from the FINEARTS-HF trial’, by Y. Hamatani, https://doi.org/10.1093/ejhf/xuag030. Patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) are typically older, multimorbid, and exposed to a substantial burden of medications.1 Polypharmacy is therefore not the exception but the norm in this population, raising persistent concerns among clinicians regarding treatment complexity, compliance, drug–drug interactions, and tolerability when introducing additional disease-modifying therapies. In contrast to heart failure with reduced ejection fraction (HFrEF), for which a well-established four-pillar pharmacological strategy exists, therapeutic options for HFpEF have historically been limited, with sodium–glucose cotransporter-2 inhibitors representing the first clearly indicated disease-modifying treatment.2 More recently, finerenone, a non-steroidal mineralocorticoid receptor antagonist, has demonstrated efficacy and safety in patients with HFpEF.3 As additional therapies, including glucagon-like peptide-1 receptor agonists,4,5 are actively being investigated, patients with HFpEF are likely to be exposed to an expanding armamentarium of disease-modifying drugs, increasingly resembling the therapeutic landscape of HFrEF. Against this backdrop, the clinical meaning and implications of polypharmacy are becoming increasingly relevant across the entire heart failure spectrum.6 In this context, understanding whether background medication burden meaningfully alters the benefit–risk profile of emerging therapies is of substantial clinical importance.