London, United Kingdom – 1 September 2024: A pooled analysis of three large trials failed to demonstrate significant reductions in cardiovascular death with finerenone, but significantly lower all-cause mortality, cardiovascular events and kidney outcomes were observed, according to late-breaking research presented in a Hot Line session today at ESC Congress 2024.1

Dr. Muthiah Vaduganathan of the Brigham and Women's Hospital and Harvard Medical School, Boston, USA, explained why the meta-analysis was conducted: “It is increasingly being recognised that cardiovascular diseases, chronic kidney disease (CKD) and metabolic conditions, such as diabetes, co-exist in the same patients and share common disease pathways. The non-steroidal mineralocorticoid receptor antagonist, finerenone, has been shown to reduce the risk of cardiovascular events and kidney failure in two trials in patients with CKD with type 2 diabetes2,3 and has recently been shown to reduce worsening heart failure (HF) events in a trial in patients with HF with mildly reduced or preserved ejection fraction.4 We combined data from these three large trials, and although we did not observe a significant reduction in cardiovascular death, all-cause mortality was significantly reduced and there were clinically relevant improvements in other outcomes.”

The participant-level pooled FINE-HEART analysis was conducted with data from the FIDELIO-DKD2 and FIGARO-DKD3 trials in patients with CKD and type 2 diabetes and the FINEARTS-HF4 trial in patients with heart failure (HF) and mildly reduced or preserved ejection fraction. The prespecified primary outcome was time to cardiovascular death. The definition of cardiovascular death differed slightly between the three trials and was harmonised for FINE-HEART as time to cardiovascular death (excluding undetermined deaths). Other prespecified outcomes included a kidney composite outcome (defined as a sustained decrease in estimated glomerular filtration rate [eGFR] to ≥50% from baseline, sustained decline in eGFR to <15 mL/min/1.73 m2, kidney failure and death due to kidney causes), HF hospitalisation, composite of cardiovascular death or HF hospitalisation, and all-cause death.

The analysis included data from 18,991 participants. The mean age was 67 years and 35% were women. At baseline, 81% had diabetes, 84% had CKD and 37% had HF, with 12% having all three conditions.

Over 2.9 years median follow-up, cardiovascular death occurred in 4.4% of patients in the finerenone group and 5.0% of patients in the placebo group (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.78–1.01; p=0.076). Death from any cause occurred in 11.0% of participants in the finerenone group and 12.0% in the placebo group (HR 0.91; 95% CI 0.84–0.99; p=0.027). Finerenone further reduced the risk of HF hospitalisation (HR 0.83; 95% CI 0.75–0.92; p<0.001) and the composite kidney outcome (HR 0.80; 95% CI 0.72–0.90; p<0.001).

The incidence of any serious adverse event was lower with finerenone than placebo (34.6% vs. 36.6%), although serious adverse events leading to drug discontinuation were higher with finerenone (5.4% vs. 4.6%). Laboratory-defined hyperkalaemia was higher with finerenone, while laboratory-defined hypokalaemia was lower.

Dr. Vaduganathan concluded: “This large, pooled analysis failed to demonstrate a significant reduction in cardiovascular death, but this may be due to the definition of cardiovascular death used and the classification of deaths of undetermined causes. We did find important reductions in all-cause death and a broad range of other cardio-kidney outcomes including kidney disease progression and HF hospitalisations. Pooling these data summarises complementary lines of evidence which support a disease-modifying potential role of finerenone across the cardio-kidney-metabolic spectrum.”

ENDS