Articles
Science Matters
In our monthly series, editorial team member Dr. Michael Katsnelson MD, PhD, FACC provides a summary of recently published clinical research article.
About the Author: Michael Katsnelson MD, PhD, FACC is currently a research fellow at Washington University in St. Louis School of Medicine. He specializes in advanced heart failure/transplant cardiology and his main research interest lies in studying the role of the innate immune system in the progression of ischemic cardiomyopathy.
Background: The development of novel pharmacologic therapies for heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmEF) remains a topic of intense research interest. Patients with HFpEF and HFmEF who experience an acute congestive heart failure (CHF) exacerbation are at increased risk for adverse outcomes including future hospitalization for heart failure exacerbation, cardiovascular death and all-cause mortality. Effective medical treatment of patients in the period immediately following an acute CHF exacerbation may result in a substantial decrease in morbidity and mortality. The current armamentarium of therapies for use in HFpEF and HFmEF patients is limited to diuretics, SGLT2 inhibitors, and management of comorbidities such as hypertension, diabetes and obesity. In a recent publication in JACC, Desai et al conducted a post-hoc analysis of the FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) trial to investigate the efficacy of the non-steroidal mineralocorticoid receptor antagonist Finerenone in patients with a recent CHF exacerbation.
Study Design: The authors utilized data from the FINEARTS-HF trial, which was a recent study comparing Finerenone vs Placebo in a population of patients with HFpEF and HFmEF. The primary outcome included cardiovascular-related death and worsening heart failure (WHF) event, which was defined as a CHF exacerbation treated in either the inpatient or outpatient setting. The authors stratified the FINEARTS-HF patients according to proximity of WHF event prior to enrollment in the trial and initiation of Finerenone therapy. The groups included those patients enrolled during or <7 days following a WHF event, >7 days but <3 months following a WHF event, and patients who either experienced a WHF event >3 months prior to enrollment or never experienced a WHF event. A key secondary endpoint included adverse renal events defined as sustained decline in GFR >50%, sustained decline in GFR to <15 ml/min/m, initiation of chronic dialysis or need for renal transplant.
Results: The authors noted that patients with HFpEF and HFmEF who were enrolled in the trial either during a WHF event or <7 days following a WHF event were at a nearly 2-fold higher risk for the composite primary outcome of subsequent acute CHF exacerbation or cardiovascular-related death compared to those patients enrolled in the trial >3 months following a WHF event or those who had no prior episodes of acute HF exacerbation. Treatment with Finerenone resulted in a larger absolute reduction in the primary outcome in those patients who were enrolled in the trial following a recent WHF event compared to those patients with a remote WHF event or no events prior to enrollment. Furthermore, there was no apparent increase in adverse events related to Finerenone in those patients enrolled in the trial <7 days following a WHF event. Specifically, rates of hyperkalemia, renal dysfunction, and systemic hypotension were similar in patients with a recent WHF event compared to those with a remote WHF event following initiation of Finerenone therapy.
Significance of Findings: The results of the FINEARTS-HF trial indicate that Finerenone is a valuable addition to diuretics and SGLT2 inhibitors in our toolkit for pharmacologic management of HFpEF and HFmEF. Furthermore, initiation of Finerenone therapy either during or soon after an episode of CHF exacerbation appears to be beneficial and safe. Patients started on Finerenone within 7 days of a CHF exacerbation derive a greater absolute benefit from mineralocorticoid receptor antagonism compared to those patients with a more remote CHF exacerbation or no prior CHF exacerbation. These findings highlight the importance of acute HF exacerbations as sentinel events and harbingers of increased risk of morbidity/mortality in patients with HFpEF and HFmEF. The study highlights the importance of intensifying medical therapy in those patients who were either recently hospitalized for congestive heart failure exacerbation or were recently seen in the clinic for worsening heart failure symptoms.
Article Link - https://www.jacc.org/doi/10.1016/j.jacc.2024.09.004
