A FIDELITY analysis presented at the European Society of Cardiology (ESC) Congress 2022 provide an overview of the cardioprotective benefits of finerenone (Kerendia) use on risk of various causes of mortality among patients with chronic kidney disease and type 2 diabetes, particularly death from cardiovascular causes.
A prespecified, exploratory analysis of individual patient data pooled from the FIDELIO-DKD and FIGARO-DKD trials, results suggest use of finerenone was associated with an 11% reduction in risk of all-cause mortality, including a 25% reduction in relative risk of sudden cardiac death.
“In this analysis of patients with type 2 diabetes and kidney disease, mortality was primarily attributed to cardiovascular events. The effect of finerenone on all-cause mortality, cardiovascular mortality and sudden cardiac death was consistent irrespective of estimated glomerular filtration rate (eGFR) or urine albumin-to creatinine ratio (UACR) at baseline, but seemingly more pronounced in patients with a higher baseline eGFR. This indicates that earlier initiation of finerenone might be warranted to maximize its protective effects in these patients,” said study presenter Gerasimos Filippatos, PhD, director of the heart failure unit at the Attikon University Hospital in Athens, Greece, in a statement.
Pooling data from FIDELIO-DKD and FIGARO-DKD, the FIDELITY program contained data from 13,026 patients with type 2 diabetes and chronic kidney disease randomized to finerenone or placebo optimally treated with a renin-angiotensin system inhibitor. The overall patient cohort had a mean age of 64.8 years, 69.8% were women, and the median follow-up time was 3.0 years. Primary analyses of FIDELITY indicated use of finerenone reduced risk of a composite cardiovascular outcome, which included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, by 14% and risk of chronic kidney disease progression by 23% (HR, 0.77 [95% CI, 0.67-0.88]) when compared against placebo therapy. In the present analysis, investigators hoped to assess rates of all-cause mortality and various other causes of mortality in the intention-to-treat population.
Results of the investigators’ analyses demonstrated all-cause mortality occurred among 8.5% (2.76 events per 100 patients-years) receiving finerenone and 9.4% (3.10 events per 100 patient-years) receiving living placebo (HR, 0.89 [95% CI, 0.79-1.00]; P=.051). Investigators pointed out the between-group difference narrowly missed statistical significance.
Investigators pointed out mortality was most often attributed to death from cardiovascular causes (4.9% vs 5.6%, respectively), followed by infection (1.5% vs 1.4%, respectively) and malignancy (1.2% vs 1.6%, respectively). When assessing individual components of cardiovascular mortality, which included sudden cardiac death, undetermined mortality, mortality due to acute myocardial infarction, heart failure, stroke, or cardiovascular procedures, or mortality due to other cardiovascular causes, results indicated use of finerenone significantly reduced the risk of sudden cardiac death compared with placebo (HR, 0.75 [95% CI, 0.57-0.996]; P=.046).
In a prespecified on-treatment analysis that included events occurring while patients were receiving treatment and for up to 30 days after the last dose of study medication, investigators found finerenone use was associated with an 18% relative reduction in all-cause (HR, 0.82 [95% CI, 0.70-0.96]; P=.014) and cardiovascular mortality (HR, 0.82 [95% CI, 0.67-0.99]; P=.040) compared with placebo.
“The most common cause of mortality was related to cardiovascular events,” Filippatos added, during his presentation at ESC Congress 2022. “Finerenone reduced the risk of all-cause cad cardiovascular mortality versus placebo, and lowered the risk of sudden cardiac death.”
This study, “Finerenone and Effects on Mortality in Chronic Kidney Disease and Type 2 Diabetes: A FIDELITY Analysis,” was presented at ESC Congress 22.