Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial.

BACKGROUND

Patients with heart failure (HF) and a recent worsening heart failure (WHF) event are known to be at high risk of recurrent hospitalization and death, regardless of ejection fraction.

OBJECTIVES

This study examined the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in relation to the recency of a WHF event.

METHODS

FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. In this prespecified analysis, we assessed the risk of cardiovascular (CV) events and response to finerenone vs placebo in relation to the time from WHF to randomization (during or within 7 days, 7 days to 3 months, >3 months, or no prior WHF). The primary outcome was a composite of total (first and recurrent) WHF events and CV death, analyzed using a proportional rates method.

RESULTS

Of 6,001 patients validly randomized to finerenone or placebo, 1,219 (20.3%) were enrolled during (749 [12.5%]) or within 7 days (470 [7.8%]), 2,028 (33.8%) between 7 days and 3 months, and 937 (15.6%) >3 months from a WHF event; 1,817 (30.3%) had no prior history of WHF. Rates of the primary composite outcome varied inversely with time since WHF, with >2-fold higher risk in those enrolled during or within 7 days of WHF compared with those enrolled >3 months from WHF or without prior WHF (risk ratio [RR]: 2.13; 95% CI: 1.82-2.55). Compared to placebo, finerenone appeared to lower the risk of the primary composite to a greater extent in those enrolled within 7 days of WHF (RR: 0.74; 95% CI: 0.57-0.95) or between 7 days and 3 months of WHF (RR: 0.79; 95% CI: 0.64-0.97) than in those >3 months from WHF or without prior WHF (RR: 0.99; 95% CI: 0.81-1.21); however, no definitive treatment-by-time interaction could be confirmed (P = 0.07). Greater absolute risk reductions with finerenone were accordingly seen in those with recent WHF (P = 0.011). The risk of adverse events including hyperkalemia and worsening renal function among patients assigned to finerenone was not increased in those with recent WHF.

CONCLUSIONS

Compared with those without recent WHF, patients with HF and mildly reduced or preserved ejection fraction who have experienced a recent WHF event are at higher risk for recurrent HF events and CV death; a possible signal of enhanced absolute treatment benefit with finerenone in this population requires further confirmation in future studies. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure EudraCT 2020-000306-29).