Treatment with the novel selective, nonsteroidal mineralocorticoid receptor antagonist finerenone has been shown to reduce the risk for clinically important cardiovascular (CV) and kidney outcomes across the spectrum of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), according to a study published in the European Heart Journal.
The FIDELITY pooled efficacy and safety analysis combined data from 2 phase 3, randomized, double-blind, placebo-controlled, multicenter trials — FIDELIO-DKD (ClinicalTrials.gov identifier: NCT02540993) and FIGARO-DKD (ClinicalTrials.gov identifier: NCT02545049). The investigators sought to conduct an individual patient-level analysis, to provide more robust estimates of the safety and efficacy of finerenone compared with placebo.
Patients with CKD and T2D were randomly assigned 1:1 to treatment with finerenone or placebo, and the results of the FIDELIO-DKD and the FIGARO-DKD trials were combined. The main time-to-event efficacy outcomes were a composite of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for heart failure, along with a composite of kidney failure, a sustained ≥57% reduction in estimated glomerular filtration rate (eGFR) from baseline over 4 weeks or longer, or renal death.
Between September 2015 and October 2018, a total of 33,292 patients from 48 countries were screened and 13,171 were randomly assigned to treatment. Ultimately, 145 patients were excluded from the study, with a total of 13,026 participants included in the analysis. The mean eGFR was 57.6 mL/min/1.73 m2 and the median urine albumin-to-creatinine ratio (UACR) was 515 mg/g. Of the study cohort, 10.2%, 41.0%, and 48.3% had moderate, high, and very high Kidney Disease Improving Global Outcomes risk scores, respectively.
The composite CV outcome occurred in 12.7% of finerenone-treated patients vs 14.4% of placebo-treated participants (hazard ratio [HR], 0.86; 95% CI, 0.78-0.95; P=.0018). Significantly lower rates of hospitalization for heart failure were reported with finerenone compared with placebo (HR, 0.78; 95% CI, 0.66-0.92; P=.0030). Incidences of CV death and nonfatal MI were directionally consistent with the CV composite outcome; the incidence of nonfatal stroke was similar in the finerenone and placebo groups. Based on a between-group risk difference of 2.2% after 3 years, 46 patients (95% CI, 29-109) would need to be treated with finerenone to prevent 1 composite CV outcome event.
The incidence of the composite kidney outcome was significantly lower with finerenone than with placebo, reported in 5.5% of finerenone-treated patients compared with 7.1% of placebo-treated patients (HR, 0.77; 95% CI, 0.67-0.88; P=.0002). Based on a between-group risk difference of 1.7% at 3 years, the number needed to treat was 60 (95% CI, 38-142). When the sustained ≥57% decrease in the eGFR component was analyzed, a 30% risk reduction was observed (HR, 0.70; 95% CI, 0.60-0.83; P<.0001). Analysis of the end-stage kidney disease component revealed a 20% risk reduction with finerenone vs placebo (HR, 0.80; 95% CI, 0.64-0.99; P=.040).
Further, the composite kidney outcome of kidney failure, sustained ≥40% eGFR decrease, or renal death was reported in 13.1% of participants in the finerenone arm and 15.3% of those in the placebo arm (HR, 0.85; 95% CI, 0.77-0.93; P =.0004). Incidences of all-cause mortality and hospitalization for any cause did not differ significantly between the finerenone and placebo groups (P =.051 and P=.087, respectively). Mean change in UACR from baseline to 4 months was 32% lower with finerenone than with placebo (95% CI, 0.66-0.70).
This study was limited by a lack of racial and ethnic diversity within the cohort, as only 4% of patients identifying as Black were included in the analysis. Additionally, patients with nonalbuminuric CKD were not included.
“The results highlight the importance of early treatment before CKD has progressed to improve outcomes in this patient population,” the investigators noted.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Agarwal R, Filippatos G, Pitt B, et al; FIDELIO-DKD and FIGARO-DKD investigators. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. Published online November 22, 2021. doi:10.1093/eurheartj/ehab777