Antagonising the mineralocorticoid receptor beneficial for patients with diabetes and CKD

The multinational FIGARO-DKD trial investigated the effect of the mineralocorticoid receptor antagonist finerone on cardiovascular outcomes in patients with mild-to-moderate chronic kidney disease (CKD) and type 2 diabetes. Finerenone decreased cardiovascular morbidity and mortality and kidney disease progression [1,2].

“I think many of us know that patients with CKD and diabetes have a high risk of hospitalisation for heart failure (HF) and cardiovascular death. In fact, patients who have both CKD and type 2 diabetes have a 3-fold risk of having HF compared with patients with diabetes alone,” explained Prof. Bertram Pitt (University of Michigan School of Medicine, MI, USA) [1].

The phase 3 FIGARO-DKD trial (NCT02545049) investigated whether the non-steroidal mineralocorticoid-receptor antagonist finerenone would reduce the cardiovascular risk in these patients [1,2]. 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 ml/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 HF. 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 had a mean age of 64 years, a mean type 2 diabetes duration of 14.5 years with a mean HbA1c of 7.7% and included 31% women. 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. Pitt 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 HF,” 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 type 2 diabetes,” Prof. Pitt concluded.

 

1. 
   
   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. N Engl J Med 2021;Aug 28. DOI:1056/NEJMoa2110956.

 

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Posted on 26 October 202117 May 2024