Cardiovascular (CV) outcomes were improved with finerenone therapy among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), according to a study published in The New England Journal of Medicine.
Researchers conducted a phase 3 clinical trial, FIGARO-DKD (ClinicalTrials.gov Identifier: NCT02545049), of patients (N=7352) with T2D and CKD in 48 countries between 2015 and 2019. Eligible participants for the study had CKD stage 1 or 2 with severely elevated albuminuria or CKD stage 2-4 with moderately elevated albuminuria. During a run-in period, patients were adjusted upward to the maximum dose of an angiotensin-converting-enzyme inhibitor or receptor blocker. Patients with no unacceptable side effects were randomly assigned 1:1 to receive 10 or 20 mg oral finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, or placebo daily. The 10 mg dose was given to patients with an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml/min/1.73 m2. The 20 mg dose was given to patients with an estimated eGFR of at least 60 ml/min/1.73 m2. From month 1, patients on the low dose were adjusted to the high dose. CV and renal outcomes were assessed through a median follow-up of 3.4 years.
The patient population comprised 69.4% men; participants had a mean age of 64.1±9.8 years; 71.8% were White; glycated hemoglobin was 7.7%±1.4%; eGFR was 67.8±21.7 ml/min/1.73 m2;and 45.3% had a history of cardiovascular disease.
The primary composite outcome of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure (HF) occurred among fewer finerenone recipients (12.4% vs 14.2%; hazard ratio [HR], 0.87; 95% CI, 0.76-0.98; P =.03).
Stratified by specific events in the primary outcome, only HF hospitalization was significantly lower among the finerenone cohort (HR, 0.71; 95% CI, 0.56-0.90).
The composite kidney outcome of kidney failure, sustained eGFR decrease of greater than or equal to 57%, or death from renal causes occurred among fewer finerenone recipients (2.9% vs 3.8%; HR, 0.77; 95% CI, 0.60-0.99).
Stratified by specific renal events, end-stage kidney disease occurred among fewer finerenone recipients (0.9% vs 1.3%; HR, 0.64; 95% CI, 0.41-0.995). The urinary albumin-to-creatinine ratio was more effectively reduced in the intervention cohort (ratio of the least-squares mean change from baseline, 0.68; 95% CI, 0.65-0.70).
Serious adverse events were reported by 31.4% of the finerenone and 33.2% of the placebo cohorts. Events led to permanent discontinuation (1.2% vs 0.4%) and hospitalization (0.6% vs 0.1%) among more of the finerenone group.
Finerenone was associated with a 0.16 mmol/l increase in serum potassium at month 1 and remained stable during the study and decreased systolic blood pressure by 3.5 mm Hg at month 4 and 2.6 mm Hg at month 24. Glycated hemoglobin and body weight were similar among groups.
This study was disrupted by the COVID-19 pandemic, in which 10 patients were lost to follow-up and 85 were excluded due to Good Clinical Practice violations.
“In the FIGARO-DKD trial, finerenone therapy improved [CV] outcomes, as compared with placebo, in patients with [T2D] who had stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria,” the study authors noted.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi:10.1056/NEJMoa2110956