CV and kidney benefits of nonsteroidal MRA irrespective of ASCVD history

Finerenone and Cardiorenal Outcomes By History Of Cardiovascular Disease In Patients With Type 2 Diabetes and Chronic Kidney Disease: Fidelity Analyses

Presented at ACC.22 by ** Gerasimos Filippatos, MD (Athens, Greece)

Introduction and methods

The selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone blocks MR overactivation, resulting in anti-inflammatory and anti-fibrotic effects on the CV system in animal models.

The FIDELIO-DKD and FIGARO-DKD trials showed that finerenone reduced risk of CV and kidney outcomes in patients with CKD and T2DM. In FIDELIO-DKD, patients with predominantly stage 3-4 CKD and moderate to severe albuminuria were enrolled, whereas a broader patient population was enrolled in FIGARO.

FIDELITY is a prespecified individual patient-data pooled analysis of the two trials including 13,171 patients with T2DM and a broad spectrum of CKD. Median follow-up was 3 years. Key outcomes were a CV composite outcome of time to CV death, nonfatal MI, nonfatal stroke or hospitalization for HF (HHF); and a kidney composite endpoint of time to kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney-related death.

This substudy examined the efficacy and safety of finerenone on CV and kidney outcomes in primary (n=7091) and secondary (n=935) prevention populations (by baseline ASCVD history).

Results

• CV benefit with finerenone was not modified by prevalent ASCVD status (in patients with a history of ASCVD: HR 0.83, 95%CI: 0.74-0.94; in patients without a history of ASCVD: HR 0.91, 95%CI: 0.78-1.06, Pinteraction=0.38).
• Finerenone reduced the risk of CV death and HHF compared with placebo irrespective of history of ASCVD status (in patients with a history of ASCVD: HR 0.82, 95%CI: 0.71-0.94; in patients without a history of ASCVD: HR 0.86, 95%CI: 0.71-1.04, Pinteraction=0.68).
• Also, the composite kidney outcome was reduced with finerenone compared with placebo irrespective of history of ASCVD status (in patients with a history of ASCVD: HR 0.71, 95%CI: 0.57-0.88; in patients without a history of ASCVD: HR 0.81, 95%CI: 0.66-0.97, Pinteraction=0.33).
• There was no significant risk reduction of all-cause mortality with finerenone in the overall FIDELITY population, and there was no modified effect by ASCVD status.
• Risk of hyperkalemia was higher in patients with finerenone, irrespective of ASCVD history.

Conclusion

In this subanalysis of FIDELITY, finerenone showed CV and kidney benefits in primary and secondary prevention groups in a patient population with CKD and T2DM. The safety profile of finerenone was similar between patients with and without a history of ASCVD.

Discussion

The discussant Rhonda Cooper-DeHoff (Gainesville, FL, USA) wondered whether there was a subset of patients on certain drugs that were more likely have adverse events to find out who to treat or not treat with finerenone in the future. Filippatos answered that the investigators did not see any drug with differential effects on outcomes. They specifically evaluated the subgroup of patients on SGLT2 inhibitors and saw no difference in outcomes.

Furthermore, he noted that it is important to evaluate these patients for UACR. 40% of patients in FIDELITY had eGFR >60, but these patients (especially those with CVD history) are at high risk of kidney outcomes. It is important for cardiologists and primary care physicians to evaluate UACR in those with preserved eGFR, but at high risk of kidney outcomes.

– Our coverage of ACC.22 is based on the information provided during the congress –