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: Patients had chronic kidney disease (eGFR of 25 ml/min/1.73 m2 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.