Real-world effectiveness and safety of finerenone in patients with chronic kidney disease and type 2 diabetes in the United States: A FOUNTAIN platform analysis

Background Finerenone is a selective, nonsteroidal mineralocorticoid receptor antagonist for treating chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). Although pivotal trials demonstrated efficacy of finerenone, evidence about real-world cardiovascular (CV) effectiveness and safety is lacking. Purpose To assess effectiveness and safety of finerenone in patients with CKD and T2D by estimating the risk of key clinical and safety outcomes in finerenone initiators compared with nonusers. Methods A new user cohort study identified adults with CKD and T2D in linked, closed administrative claims, electronic health records, and laboratory data from the US. Finerenone initiators were propensity-score matched with nonusers (nonusers anchored on the date of a recorded CKD diagnosis; multiple dates per individual allowed). Patients were followed until study end, loss to follow-up, or deviation from the treatment strategy. Effectiveness outcomes included composite CV outcome (hospital diagnosis of acute myocardial infarction [AMI] or hospitalization for heart failure [HF]); individual components of the composite outcome; new-onset HF; and all-cause mortality. The safety outcome was hyperkalemia. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in matched cohorts using Cox proportional hazards models with inverse probability of censoring (IPC) weights. Time-specific risk ratios (RRs) and risk differences (RDs) were estimated from the IPC-weighted cumulative incidence function. Subgroup analyses were performed by key demographic and clinical factors. Results We identified 14,287 eligible finerenone initiators and 57,148 matched nonusers overall (mean age, 66 years; male, 53%). After matching, baseline characteristics were well balanced between treatment groups (e.g., 28% in each group with congestive HF; 24% with cerebrovascular disease). Finerenone initiators had lower risk of the composite CV outcome (HR, 0.89; 95% CI, 0.79-1.00), driven by a lower risk of HF hospitalization (HR, 0.84; 95% CI, 0.73-0.96). HRs for AMI, new-onset HF, and all-cause mortality were attenuated or null. Finerenone initiators were more likely to experience hyperkalemia (HR, 1.47; 95% CI, 1.31-1.65). Time-specific RR estimates closely aligned with the HR estimates. RD estimates demonstrated reduction in risk of composite CV and HF hospitalization outcomes throughout follow-up. Results were generally consistent across subgroups. Conclusions In real-world patients with CKD and T2D, finerenone initiators had a reduced risk of HF hospitalizations. Finerenone was associated with an increased risk of hyperkalemia.