Year: 2025
Type: article
Abstract: Importance: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these. Objective: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). Design, Setting, and Participants: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries. Patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of 40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized between September 2020 and January 2023. Data analysis was conducted from October 1 to November 30, 2024. Intervention: Addition of once-daily finerenone or placebo to usual therapy. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death and total worsening HF events. Frailty was measured using the Rockwood cumulative deficit approach. Results: Of the 6001 patients randomized in FINEARTS-HF, a frailty index (FI) was calculable in 5952 patients (mean [SD] age, 72.0 [9.6] years; 3241 [54.4%] male). In total, 1588 patients (26.7%) had class I frailty (FI ≤0.210 [not frail]), 2141 (36.0%) had class II frailty (FI 0.211-0.310 [more frail]), and 2223 (37.3%) had class III frailty (FI ≥0.311 [most frail]). Compared with patients with class I frailty, those with class II and III frailty had a higher risk of the primary outcome (unadjusted rate ratio [RR], 1.88 [95% CI, 1.54-2.28] for class II and 3.86 [95% CI, 3.22-4.64] for class III). The effect of finerenone on the primary outcome did not vary significantly by frailty class (class I: RR, 1.07 [95% CI, 0.77-1.49]; class II: RR, 0.66 [95% CI, 0.52-0.83]; class III: RR, 0.91 [95% CI, 0.76-1.07]; P for interaction = .77). Frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. The effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class. Conclusions and Relevance: In FINEARTS-HF, finerenone reduced the risk of total worsening HF events and cardiovascular death, and it improved symptoms; these effects were not modified by frailty status. In addition, the effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status. Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.
Source: JAMA Cardiology
Authors: Jawad H. Butt, Pardeep S. Jhund, Alasdair D. Henderson, Brian L. Claggett, Chern-En Chiang, Gerard C. M. Linssen, Clara I. Saldarriaga, Jose F. K. Saraiva, Naoki Sato, Morten Schou, Dirk von Lewinski, James Lay-Flurrie, Andrea Scalise, Katja Rohwedder, Akshay S. Desai, Carolyn S. P. Lam, Michele Senni, Sanjiv J. Shah, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John J. V. McMurray
Institutions: University of Glasgow, Brigham and Women's Hospital, Harvard University, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, Ziekenhuis Groep Twente, Clínica Santa María, Herlev Hospital, Gentofte Hospital, Medical University of Graz, Bayer (United Kingdom), Bayer (Germany), National University of Singapore, National Heart Centre Singapore, Ospedale Papa Giovanni XXIII, University of Milano-Bicocca, Northwestern University, Inserm, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, University of Michigan
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4411413487