Efficacy and safety of finerenone in patients with an acute change in estimated glomerular filtration rate in the prespecified FIDELITY pool analysis

INTRODUCTION: The efficacy and safety of finerenone (a nonsteroidal mineralocorticoid receptor antagonist) versus placebo were assessed according to different changes in estimated glomerular filtration rate (eGFR) using data from FIDELITY, a pooled individual-level analysis of two clinical trials. METHODS: or greater) and type 2 diabetes with optimized renin-angiotensin system blockade. Risk of composite cardiovascular and composite kidney outcomes was analyzed by baseline eGFR change at month one in the total population and by treatment group. RESULTS: Of 12,798 patients, 25.1% had a >10% eGFR decline, 31.2% had a >0-10% decline, 26.8% had a 0-10% increase, and 16.8% had a >10% increase after one month of treatment. Factors associated with acute eGFR decline included higher baseline urine albumin-to-creatinine ratio, eGFR, systolic blood pressure, diuretic or beta-blocker use, and finerenone use. Finerenone significantly reduced composite cardiovascular and kidney outcomes overall and had similar beneficial effect across eGFR subgroups of >10% decline, >0-10% decline, 0-10% increase, and >10% increase for composite cardiovascular (hazard ratio 95% Confidence Interval of 0.74 0.61-0.90, 0.87 0.73-1.04, 1.06 0.87-1.28, and 0.78 0.61-0.99, respectively) and kidney outcomes (0.67 0.53-0.85, 0.78 0.61-1.01, 0.56 0.40-0.77, and 0.75 0.50-1.14, respectively) (P interaction 0.048 and 0.23, respectively). When modeled as a continuous variable, finerenone reduced the risk of cardiovascular and kidney outcomes, irrespective of acute eGFR change (P interaction 0.58 and 0.36, respectively). CONCLUSIONS: The cardiovascular and kidney benefits of finerenone were not modified by an acute eGFR change after drug initiation.