Abstract Body (Do not enter title and authors here):
Background: The nonsteroidal mineralocorticoid receptor antagonist finerenone has been shown to reduce adverse clinical outcomes in persons with heart failure (HF) and chronic kidney disease (CKD) with type 2 diabetes. However, the relative timing of these benefits has not been evaluated.

Research Question: What is the timing of cardiovascular and kidney protection with finerenone?

Methods: In this participant-level analysis of randomized, placebo-controlled, phase 3 outcomes trials evaluating finerenone in persons with HF (FINEARTS-HF) and CKD with type 2 diabetes (FIGARO-DKD and FIDELIO-DKD [FIDELITY]), we evaluated the cumulative number and type of clinical outcomes (time-to-first) prevented over time post-randomization. The timing of first statistically significant benefit of finerenone on selected clinical outcomes was additionally assessed. Estimates of events prevented (per 10,000 treated participants) were calculated using the difference in observed events between treatment arms, and were displayed graphically.

Results: In both trial populations, benefits with finerenone occurred early and accrued over time (Figure). In both FIDELITY and FINEARTS-HF, HF hospitalization appeared to be the earliest type of event prevented. In FIDELITY, time to first nominal statistical significance for HF hospitalization was 6.1 months (HR, 0.65; 95% CI, 0.43 to 0.999), compared with 10.2 months (HR, 0.59; 95% CI, 0.35 to 0.98) for the composite kidney outcome (Figure). Similarly, first statistical significance for HF hospitalization in FINEARTS-HF was attained after 0.9 months (HR, 0.55; 95% CI, 0.32 to 0.96). At 12 months, we estimated 67 and 140 HF hospitalizations per 10,000 patients would be prevented with finerenone vs. placebo, based on findings from FIDELITY and FINEARTS-HF, respectively (Figure). While kidney benefits in FIDELITY were initially slower to accumulate compared with cardiovascular benefits, the number of kidney events prevented (216 per 10,000 patients) exceeded the number of cardiovascular events prevented (180 per 10,000 patients) by 43 months (Figure).

Conclusions: These findings underscore the high short-term risks of HF events in persons with cardiovascular, kidney, and/or metabolic conditions, which are modifiable with finerenone. When used in CKD management, finerenone prevents cardiovascular events even prior to modifying longer-term risks of kidney disease progression.