Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a fidelity analysis

Presented at the ESC congress 2022 by: Prof. Gerasimos Filippatos, MD- Athens, Greece

Introduction and methods

The life expectancy of patients with both T2DM and CKD is about 16 years shorter than that of those without these diseases. Most of these deaths can be attributed to CVD. Although steroidal MRAs have been shown to reduce CV mortality in HF patients, their use is limited by off-target side effects.

The previous FIDELITY analysis showed CV and kidney benefits of the selective, nonsteroidal MRA finerenone over placebo in 13,026 T2DM patients with CKD during a median follow-up time of 3 years. The current exploratory subanalysis assessed the causes of mortality, its key outcomes being all-cause mortality and CV mortality (including sudden cardiac death).

Main results

• In the intention-to-treat analysis, finerenone did not change the risk of all-cause mortality compared with placebo (hazard ratio (HR): 0.89; 95%CI: 0.79–1.00; P=0.051) or the CV mortality risk (HR: 0.88; 95%CI: 0.76–1.02; P=0.092), but it did reduce the risk of sudden cardiac death (relative risk reduction (RRR): 25%; HR: 0.75; 95%CI: 0.57–0.996; P=0.046).
• In the prespecified on-treatment analysis, finerenone decreased the all-cause mortality risk compared with placebo (RRR: 18%; HR: 0.82; 95%CI: 0.70–0.96; P=0.014) and the CV mortality risk (RRR: 18%; HR: 0.82; 95%CI: 0.67–0.99; P=0.040).
• The effect of finerenone on mortality outcomes was consistent irrespective of eGFR or urine albumin-to-creatinine ratio at baseline, although it was seemingly more pronounced in patients with a higher baseline eGFR.

Conclusion

In the prespecified exploratory FIDELITY subanalysis, finerenone showed no reduction of the incidence of all-cause and CV mortality in the intention-to-treat analysis, but a reduction on these two endpoints was observed in the on-treatment analysis. The analysis further showed that finerenone reduced the risk of sudden cardiac death in theintention-to treat analysis compared with placebo in T2DM patients across a broad spectrum of CKD severity.

-Our reporting is based on the information provided at the ESC Congress-