Finerenone-Related Risk of Hypotension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.

Abstract

BACKGROUND: The nonsteroidal mineralocorticoid receptor antagonist finerenone reduces clinical events in heart failure with mildly reduced ejection fraction/preserved ejection fraction; however, the implications of treatment-related hypotension are unknown. OBJECTIVES: The authors investigated predictors of systolic blood pressure (SBP) <100 mm Hg and investigator-reported hypotension and their associations with randomized treatment and clinical outcomes in the FINEARTS-HF (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke]) trial. METHODS: FINEARTS-HF was a randomized, placebo-controlled trial of finerenone in symptomatic patients with chronic heart failure (left ventricular ejection fraction &#x2265;40%). Predictors of SBP <100 mm Hg and hypotension were identified using Cox models. Associations between SBP <100 mm Hg and hypotension, treatment, and clinical outcomes were evaluated using time-updated Cox models. The primary outcome was a composite of total heart failure events and cardiovascular death. RESULTS: Among the 5,815 participants with available data, post-baseline SBP <100 mm Hg occurred in 899 (538 with finerenone vs 361 with placebo; odds ratio: 1.60; 95% CI: 1.38-1.85) and investigator-reported hypotension in 364 patients (225 with finerenone vs 139 with placebo; odds ratio: 1.67; 95% CI: 1.34-2.08). Participants experiencing SBP <100 mm Hg had lower baseline SBP, were older, had higher N-terminal pro-B-type natriuretic peptide levels, a history of smoking, and no diabetes. Treatment-related risk of the primary endpoint was reduced in patients with no/before SBP <100 mm Hg (rate ratio: 0.78; 95% CI: 0.67-0.90) and appeared to attenuate afterwards (rate ratio: 0.99; 95% CI: 0.70-1.39), although no formal statistical interaction was observed (Pinteraction = 0.33). CONCLUSIONS: In this prespecified analysis of the FINEARTS-HF trial, finerenone led to higher rates of post-baseline SBP <100 mm Hg and investigator-reported hypotension. Although hypotension should not prompt automatic treatment discontinuation, these patients should be carefully monitored. (Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone 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).