FINE-HEART: Effects of finerenone on morbidity and mortality in CKD

Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease and premature mortality. The risks of CKD progression and CKD-related complications increase with concomitant type 2 diabetes. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is now recommended for people with type 2 diabetes, CKD and albuminuria, but more evidence may provide further information on its safety and efficacy within this population.

Three large trials, FIDELIO-DKD, FIGARO-DKD and FINEARTS-HF, have assessed the effects of finerenone on outcomes in a population encompassing a wide range of cardiovascular and kidney disease. Previous FINE-HEART analyses of pooled data from these trials have evaluated the safety and efficacy of finerenone. In a further pre-specified analysis of the data, Ostrominski and colleagues investigated its effects on morbidity and mortality in participants with type 2 diabetes and albuminuric CKD.

Trial participants from FINEARTS-HF with type 2 diabetes, CKD and albuminuria were pooled with participants from FIDELIO-DKD and FIGARO-DKD with type 2 diabetes and CKD. Participants in each of the three trials were randomly allocated to finerenone or placebo, and the treatment effects on cardiovascular events, composite kidney outcomes, all-cause hospitalisation and mortality evaluated. Included in the analysis were 14,180 participants (mean age, 65±10 years; 31% female; mean eGFR, 58±22 mL/min/1.73 m²; median UACR, 478 [IQR, 167–1103] mg/g). 

Over a median follow-up of 3.0 years, cardiovascular death or heart failure hospitalisation was reduced in the finerenone arm compared with the placebo arm (HR, 0.83 [95% CI, 0.75–0.93; P=0.001]). These effects were consistent across trials and other subgroups, and across the range of baseline eGFR (P_interaction=0.18), UACR (P_interaction=0.60) and HbA_1c (P_interaction=0.51).

Additionally, finerenone reduced risk of heart failure hospitalisation (HR, 0.81 [0.71–0.93; P=0.05]) and appeared to reduce cardiovascular death (HR, 0.84 [0.71–1.00; P=0.05]). Finerenone also reduced major adverse cardiovascular events, new-onset atrial fibrillation and the composite kidney outcome. Regarding composite kidney outcome, the greater benefits were observed at higher levels of UACR (P_interaction=0.04).

In sensitivity analyses involving a broader range of participants with CKD, finerenone appeared to consistently reduce cardiovascular death or heart failure hospitalisation. This was irrespective of UACR (P_interaction=0.22) when FINEARTS-HF participants with type 2 diabetes and at least moderate-risk CKD were included, and of HbA_1c (P_interaction=0.59) when FINEARTS-HF participants with albuminuric CKD, but without diabetes, were included.

The incidence of serious adverse events was lower with finerenone compared with placebo (34% vs 36%), although hyperkalaemia-related treatment discontinuations were more common (18% vs 8%). 

The findings that finerenone appears to improve morbidity and mortality across a wide spectrum of CKD in people with type 2 diabetes highlights the potential for clinically relevant benefits in broader populations with CKD, including those with lower levels of albuminuria or without diabetes.

The full article can be read here.