Abstract
Background: An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF).
Objectives: The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone.
Methods: In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo. The primary outcome was the composite of total HF events and cardiovascular death.
Results: Among 5,587 patients with an eGFR measurement at both baseline and 1 month, 1,018 (18.2%) experienced a ≥15% decline in eGFR. The proportion of patients experiencing a ≥15% decline in eGFR was 23.0% with finerenone and 13.4% with placebo (OR: 1.95; 95% CI: 1.69-2.24; P < 0.001). After adjustment, an eGFR decline was associated with a higher risk of the primary outcome in patients assigned to placebo (adjusted rate ratio: 1.50; 95% CI: 1.20-1.89) but not in those assigned to finerenone (adjusted rate ratio: 1.07; 95% CI: 0.84-1.35; Pinteraction = 0.04). By contrast, the efficacy of finerenone was consistent across the range of change in eGFR from baseline to 1 month (Pinteraction = 0.50 for percent change in eGFR), and safety, including hyperkalemia, was similar regardless of an early eGFR decline.
Conclusions: Although an initial decline in eGFR was associated with worse outcomes in patients assigned to placebo, this relationship was not as strong in those treated with finerenone. An early decline in eGFR can be anticipated with finerenone and should not automatically lead to the discontinuation of this disease-modifying therapy (FINEARTS-HF Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure [NCT04435626]; A Multicenter, Randomized, Double-Bline, Parallel-Group, Placebo-Controlled Study to Evaluate the efficacy and safety of finerenone on morbidity and mortality in participants With Heart Failure [NYHA II-IV] and left ventricular ejection fraction ≥40% [EudraCT 2020-000306-29]).