The multinational FIGARO-DKD trial investigated the effect of mineralocorticoid receptor antagonist treatment on cardiovascular outcomes in patients with mild-to-moderate kidney disease and type 2 diabetes (T2D). Finerenone decreased cardiovascular morbidity and mortality and kidney disease progression1,2.
The risk of hospitalisation for heart failure and cardiovascular death is markedly increased in patients with chronic kidney disease (CKD) and T2D. The FIGARO-DKD trial (NCT02545049) investigated whether finerenone would reduce the cardiovascular risk in these patients. After a run-in phase of 4–16 weeks, during which the renin-angiotensin system inhibition therapy of the patients was optimised, the study randomised 7,437 adults to finerenone 10 mg/20 mg daily or placebo.
Among the inclusion criteria was an eGFR ≥25 mLl/min/1.73 m², urine albumin to creatinine ratio (UACR) ≥30–≤5,000 mg/g and a serum potassium of ≤4.8 mmol/L. The primary endpoint was composed of cardiovascular death, non-fatal myocardial infarction, and hospitalisation for heart failure. Secondary composite endpoints looked at a decrease in eGFR of ≥40% and ≥57% or renal death, as well as the development of end-stage renal disease.
The study cohort included predominantly men, had a mean age of 64 years, and a mean T2D duration of 14.5 years with a mean HbA1c of 7.7%. All participants had a renin-angiotensin system blocker, 71% received statins, 48% β-blockers, and 51% calcium antagonists. Importantly, at least 60% of patients with a preserved eGFR had albuminuric CKD with a UACR of ≥30mg/g. Prof. Bertram Pitt (University of Michigan School of Medicine, MI, USA) reminded his colleagues not to forget to screen for UACR even when eGFR is normal.
The risk for the primary endpoint was significantly reduced in the finerenone arm of the study by 13%, demonstrated by a hazard ratio of 0.87 (95% CI 0.76–0.98; P=0.026). “I’d like to emphasise that this was primarily driven by a 29% reduction in hospitalisation for heart failure,” stated Prof. Pitt. The composite kidney outcome of a ≥40% reduction was non-significant (P=0.069). “However, the more reliable and classic endpoint, a greater than 57% reduction in eGFR, an endpoint that has been used in many renal trials, was significantly reduced and, most importantly for our patients, the progression to end-stage renal disease was also significantly reduced. So, significantly less dialysis and end-stage renal disease,” highlighted Prof. Pitt.
The overall adverse-event profile was balanced between the groups, but hyperkalaemia occurred about twice as often in the finerenone group (10.8%) compared with the placebo group (5.3%). Of note, only 1.2% of patients on finerenone had to discontinue the medication due to hyperkalaemia. “Together, the results of FIGARO-DKD and the previous FIDELIO-DKD (NCT02540993) allow us to say pretty confidently: finerenone provides kidney and CV benefits across the spectrum of patients with CKD and T2D,” Prof. Pitt concluded.
1. Pitt B. FIGARO-DKD: Finerenone in patients with chronic kidney disease and type 2 diabetes. Hot Line Session, ESC Congress 2021, 27–30 August.
2. Pitt B. New Engl J Med 2021;28 Aug. DOI: 10.1056/NEJMoa2110956.