Debra L. Beck, MSc, and Eugene Braunwald, MD

Mineralocorticoid receptor antagonists (MRA) have a class IA recommendation in patients with heart failure with reduced ejection fraction (HFrEF) but are not commonly used in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), in part because there have been no prospective evaluation of their effects in this population. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal MRA) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. Filippatos and colleagues have conducted prespecified analyses of FIGARO-DKD to assess the impact of finerenone on clinically-important HF outcomes.

Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m², or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m²,) were randomized to finerenone or placebo. Patients with chronic symptomatic HFrEF (NYHA class II-IV) at the run-in visit (a class IA recommendation for an MRA) were excluded.

Overall, 7352 patients were included in these analyses, from whom 571 (7.8%) had a history of HF at baseline. Patients with a history of HF were more likely to be female, with a higher body mass index, higher level of hs-CRP, lower heart rate, and lower eGFR and UACR. They also had a longer mean duration of diabetes and were more likely to have a history of atherosclerotic cardiovascular disease.

New-onset HF was significantly reduced with finerenone versus placebo (1.9% vs. 2.8%; hazard ratio [HR], 0.68; p=0.02).

Overall, all HF-related outcomes were lower with finerenone compared to placebo. This included an 18% lower risk of cardiovascular death or first hospitalization for HF (HR, 0.82; P=0.01) and a 29% lower risk of first hospitalization for HF (HR, 0.71 [95% CI 0.56-0.90]; P=0.0043).

The benefits of finerenone on HF outcomes were not modified by a history of HF at baseline. There were no differences in incidence of treatment-emergent adverse events in those with and without HF. Treatment-emergent hyperkalemia was more common in those treated with finerenone.

Summary

The investigators concluded that, based on these prespecified FIGARO-DKD analyses, the selective MRA finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF. “This is the first indication that a nonsteroidal mineralocorticoid receptor antagonist may provide benefit in a population with CKD and T2D in which patients with HF with reduced ejection fraction and New York Heart Association class II–IV were excluded, indicating that patients with CKD in T2D at risk of HF or early-stage HF may benefit from finerenone treatment,” wrote Filippatos et al.

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