A biomarker-driven risk model accurately stratified outcomes in patients with heart failure and preserved or mildly reduced ejection fraction, and baseline risk did not modify the relative effect of finerenone, according to a prespecified secondary analysis of a randomized trial.
Researchers analyzed 6,001 patients in the FINEARTS-HF trial (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), in which patients aged 40 years or older with symptomatic heart failure and left ventricular ejection fraction of 40% or greater were randomized to finerenone or placebo and followed for a median of 32 months. The analysis was led by Misato Chimura, MD, PhD, of the University of Glasgow, United Kingdom, and Osaka University Graduate School of Medicine, Japan, and colleagues.
Event rates increased stepwise across risk quintiles using the EMPEROR-Preserved risk model (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), which incorporates biomarkers and clinical variables. For the composite of first heart failure hospitalization or cardiovascular death, rates rose from 2.2 per 100 patient-years in the lowest-risk quintile to 25.0 per 100 patient-years in the highest-risk quintile, corresponding to an approximately 10-fold gradient in risk. Cardiovascular death showed a similar pattern, with an approximately 13-fold gradient between the highest- and lowest-risk groups.
The model demonstrated good discrimination and generally preserved calibration across outcomes, although estimated risk modestly exceeded observed risk in the highest-risk quintile. Similar graded associations were observed for total heart failure events and all-cause death across both categorical and continuous risk distributions.
Finerenone reduced the composite of heart failure hospitalization or cardiovascular death consistently across risk quintiles, with hazard ratios ranging from 0.93 in the lowest-risk group to 0.88 in the highest-risk group and no evidence of interaction across the risk spectrum.
Absolute benefit varied by baseline risk. Estimated absolute risk reduction for the primary outcome was 3.7 events per 1,000 patient-years in the lowest-risk quintile compared with 43.0 per 1,000 patient-years in the highest-risk quintile, corresponding to numbers needed to treat of 272 vs 23.
In the placebo group, the incidences of hyperkalemia and elevated creatinine increased across higher-risk quintiles. Overall, hypotension, elevated creatinine, and hyperkalemia were more common with finerenone than placebo, whereas hypokalemia was less common with finerenone. The magnitude of differences between treatment groups was consistent across all risk categories.
Patients in higher-risk categories were older and had lower ejection fraction, kidney function, body mass index, and symptom scores, along with higher prevalence of atrial fibrillation, stroke, and prior heart failure hospitalization.
Limitations included potential residual confounding or unmeasured heterogeneity, limited power for subgroup interaction analyses, and restricted generalizability due to trial selection criteria. One variable required for the risk model was unavailable and imputed, which may have affected predictive performance.
The researchers reported that “baseline risk did not modify the relative treatment effect of finerenone.”
The findings were also presented at the American College of Cardiology 75th Annual Scientific Session.
The study was funded by Bayer AG. Multiple researchers reported relationships with pharmaceutical companies, including consulting fees, grants, advisory roles, and employment with Bayer AG.
Source: JAMA Cardiology
