Safety and Tolerability of the Novel Non-Steroidal Mineralocorticoid Receptor Antagonist BAY 94-8862 in Patients With Chronic Heart Failure and Mild or Moderate Chronic Kidney Disease: A Randomized, Double-Blind Trial
What is the safety and tolerability of BAY 94-8862, a next-generation nonsteroidal mineralocorticoid receptor antagonist (MRA) with improved selectivity for the mineralocorticoid receptor (MR) over other steroid hormone receptor, compared with spironolactone 25-50 mg/day, in patients with chronic heart failure (HF) and a reduced left ventricular ejection fraction (HFrEF) with New York Heart Association class II-III symptoms and mild to moderate chronic kidney disease (CKD)?
ARTS (minerAlocorticoid Receptor Antagonist Tolerability Study) was a multicenter, international, randomized, parallel-group, phase II study conducted in two parts. In part A, the safety and tolerability of oral BAY 94-8862 in patients with HFrEF and mild CKD (estimated glomerular filtration rate [eGFR] 60 to <90 ml/min/1.73 m2) was compared to those taking placebo by determining the effects on serum potassium concentration, eGFR, and albuminuria. In part B, BAY 94-8862 was compared with placebo and open-label spironolactone in 392 patients with HFrEF and moderate CKD (eGFR 30 to <60 ml/min/1.73 m2). The primary endpoint in part B was the change in serum potassium concentration. The impact of BAY 94-8862 on systolic blood pressure and B-type natriuretic peptide (BNP) was also assessed. In both parts of the study, patients received the study drug for 4 weeks.
The mean increases in serum potassium concentration were significantly smaller in all four BAY 94-8862 dose groups than in the spironolactone group. Compared to spironolactone, BAY 94-8862 was associated with lower incidences of hyperkalemia (5.3% and 12.7%, respectively, p = 0.048) and worsening renal function. BAY 94-8862 decreased the levels of BNP at least as much as did spironolactone.
BAY 94-8862, a next-generation nonsteroidal MRA, is at least as effective as spironolactone in decreasing serum BNP, and is associated with lower incidences of hyperkalemia and worsening renal function.
The first randomized clinical trial of BAY 94-8862 shows promise for this next-generation nonsteroidal MRA. These phase II results should pave the way for future clinical studies that continue to elucidate the potential clinical benefits of this therapy in HFrEF.
Keywords: Receptors, Mineralocorticoid, Heart Failure, Stroke Volume, Hyperkalemia, Blood Pressure, Spironolactone, Renal Insufficiency, Chronic, Naphthyridines, Natriuretic Peptide, Brain
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