Balcinrenone plus dapagliflozin in patients with heart failure and chronic kidney disease: Results from the phase 2b MIRACLE trial.
In the phase 2b MIRACLE trial, adding the novel mineralocorticoid receptor modulator balcinrenone to dapagliflozin did not significantly reduce albuminuria compared with dapagliflozin alone in patients with heart failure and chronic kidney disease.
Background
Approximately half of patients with heart failure also have chronic kidney disease, and many cannot tolerate steroidal mineralocorticoid receptor antagonists because of hyperkalemia and worsening renal function. Balcinrenone is a novel mineralocorticoid receptor modulator developed to retain cardio-renal benefit while limiting these risks.
Study design
MIRACLE randomized 133 adults with symptomatic heart failure, ejection fraction below 60%, eGFR of 30 to 60 ml/min/1.73 m2, and a urinary albumin-to-creatinine ratio of 30 to under 3000 mg/g to balcinrenone 15, 50, or 150 mg/day plus dapagliflozin 10 mg/day, or dapagliflozin plus placebo, for 12 weeks. The primary endpoint was the relative reduction in urinary albumin-to-creatinine ratio from baseline to week 12; enrollment was stopped early because of slow recruitment.
Key findings
Reductions in urinary albumin-to-creatinine ratio were not significantly different between the balcinrenone plus dapagliflozin groups and dapagliflozin plus placebo, with no clear dose-response relationship. There were possible dose-dependent increases in serum potassium, reduced eGFR in the highest-dose group, and non-significant trends toward lower NT-proBNP; hyperkalemia led to discontinuation in two balcinrenone-treated participants.
Clinical implications
The smaller-than-planned sample size limits interpretation, and the trial did not demonstrate an albuminuria benefit of adding balcinrenone to dapagliflozin in this population. Findings are hypothesis-generating and underscore the need for adequately powered studies to define the role of this novel agent in cardio-renal disease.
Category
Research
Source
Eur J Heart Fail
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