Finerenone decreases hospitalization for heart failure in patients with type 2 diabetes and chronic kidney disease (NNT = 189/year)

Reference

Pitt B, Filippatos G, Agarwal R, et al, for the FIGARO-DKD Investigators. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 2021;385(24):2252-2263.

Synopsis

Finerenone is a mineralocorticoid receptor antagonist thought to reduce inflammation caused by overactivation of these receptors by aldosterone and cortisol. Such overactivation and inflammation is associated with renal disease and cardiovascular disease. For this trial, the authors recruited adults with chronic kidney disease (CKD) and type 2 diabetes who were taking the maximal tolerated dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). CKD was defined by a urinary albumin-creatinine ratio of 30 to 300 and an estimated glomerular filtration ratio (eGFR) of 25 to 90 mLmin/1.73m2 (stage 2, 3, or 4 CKD) or a urinary albumin-creatinine ratio of 300 to 5000 and an eGFR of greater than 60 mL/min/1.73m2 (stage 1 or 2 CKD). Persons with symptomatic heart failure with reduced ejection fraction were excluded. Participants were randomized to receive finerenone at an initial dose of either 10 mg or 20 mg, depending on renal function, or placebo. The dose was titrated upward, if possible, as long as the potassium level did not increase above 4.8 mmol/L. The groups were balanced at baseline, though it is not clear whether allocation was concealed. The mean age of participants was 64 years, with a mean GFR of 68 mL/min/1.73m2 and a mean urinary albumin-creatinine ratio of 308. A total of 7437 persons were randomized, and after the exclusion of 85 patients because of research misconduct, 7352 persons were ultimately included in the intention-to-treat analysis. After a median follow-up of 3.4 years, the primary outcome of the composite of major adverse cardiovascular events was significantly reduced (12.4% vs 14.2%; P = .03; number needed to treat [NNT] = 189 per year). However, this was driven almost entirely by a reduction in hospitalizations for heart failure, with no significant reduction in cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke. The likelihood of end-stage kidney disease, defined as the need for dialysis or transplant, was slightly lower in the treatment group (0.9% vs 1.3%; P < .05; NNT = 714 per year). Serious adverse events were rare and were not different between groups, although hyperkalemia occurred more often in the finerenone group (6.5% vs 3.1%; number needed to treat to harm = 29).