Finerenone reduces CKD progression, CV risk

Treatment with the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone reduced chronic kidney disease (CKD) progression and cardiovascular (CV) event risk in patients with CKD and type 2 diabetes (T2D), according to the FIDELIO-DKD* study presented at ASN Kidney Week 2020.

This multinational, phase III, double-blind trial included 5,734 adults with CKD** and T2D on maximally tolerated renin-angiotensin system blockers, and with baseline serum potassium levels ≤4.8 mmol/L (mean 4.37 mmol/L). They were randomized 1:1 to receive finerenone (starting dose 10 mg QD for patients with eGFR 25 to <60 mL/min/1.73 m² and 20 mg QD for eGFR ≥60 mL/min/1.73 m²) or placebo and were followed up for a median 2.6 years. The final analysis included 5,674 patients (mean age 65.6 years, 70.2 percent male, 63.3 percent White). Mean baseline eGFR was 44.3 mL/min/1.73 m².

There was a significant reduction in the incidence of the primary composite outcome of kidney failure***, sustained (≥4 weeks) eGFR decrease of ≥40 percent from baseline, and renal-related mortality in the finerenone vs placebo group (17.8 percent vs 21.1 percent; hazard ratio [HR], 0.82, 95 percent confidence interval [CI], 0.73–0.93; p=0.001). [ASN Kidney Week 2020, abstract FR-OR51; N Engl J Med 2020;doi:10.1056/NEJMoa2025845]

The secondary composite outcome of CV-related death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization was also reduced with finerenone vs placebo (13.0 percent vs 14.8 percent; HR, 0.86, 95 percent CI, 0.75–0.99; p=0.03).

This translated to needing to treat 29 and 42 patients with finerenone to prevent one primary and secondary composite outcome, respectively.

All-cause mortality did not significantly differ between the finerenone and placebo groups (7.7 percent vs 8.6 percent; HR, 0.90). UACR change from baseline to month 4 was reduced with finerenone vs placebo (least squares [LS] mean change, 0.69). Fewer patients in the finerenone than placebo group experienced the kidney composite outcome of kidney failure, sustained (≥4 weeks) decrease in eGFR of ≥57 percent from baseline, or renal-related death (8.9 percent vs 11.5 percent; HR, 0.76).

Adverse events (AEs) occurred in a comparable proportion of finerenone and placebo recipients (87.3 and 87.5 percent, respectively). Serious AEs occurred in 31.9 and 34.3 percent, respectively, were related to the trial regimen in 1.7 and 1.2 percent, respectively, and led to discontinuation in 2.7 and 2.8 percent, respectively. Acute kidney injury-related AE rates were similar in the two groups. Hyperkalaemia incidence was more common with finerenone than placebo (18.3 percent vs 9.0 percent), and more often led to discontinuation with the former, though none of the incidents were fatal. Serum potassium elevation to >5.5 and >6.0 mmol/L was more common in the finerenone than placebo group.

“These results suggest that in patients with CKD and T2D, finerenone may be an effective treatment for kidney and CV protection,” said the researchers. “[T]he benefits of finerenone were observed after 12 months for the kidney outcome and as early as 1 month for the CV outcome, and … persisted throughout the trial.”

There could be multiple reasons behind these outcomes, they continued. “[S]ome benefits of finerenone may partly be mediated by natriuretic mechanisms,” they said, pointing out the early effects on albuminuria and the secondary outcome and modest reduction in systolic blood pressure (mean change, -3.0 and -2.1 mm Hg from baseline to month 1 and 12, respectively) without apparent effects on HbA_1c or body weight. However, the effects of finerenone on delaying CKD progression could also be due to an impact on tissue remodeling, they said.