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.
Author(s): Pitt B(1), Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C,
Kolkhof P, Kim SY, Zannad F.
Affiliation(s): Author information:
(1)University of Michigan School of Medicine, Ann Arbor, MI, USA.
bpitt@med.umich.edu
Publication date & source: 2013, Eur Heart J. , 34(31):2453-63
AIMS: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients
with heart failure and reduced left ventricular ejection fraction (HFrEF), but
their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY
94-8862 is a highly selective and strongly potent non-steroidal MRA. We
investigated its safety and tolerability in patients with HFrEF associated with
mild or moderate chronic kidney disease (CKD).
METHODS AND RESULTS: This randomized, controlled, phase II trial consisted of two
parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10
mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In
part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared
with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with
HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller
mean increases in serum potassium concentration than spironolactone (0.04-0.30
and 0.45 mmol/L, respectively, P < 0.0001-0.0107) and lower incidences of
hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862
decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP,
and albuminuria at least as much as spironolactone. Adverse events related to BAY
94-8862 were infrequent and mostly mild.
CONCLUSION: In patients with HFrEF and moderate CKD, BAY 94-8862 5-10 mg/day was
at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers
of haemodynamic stress, but it was associated with lower incidences of
hyperkalaemia and WRF.
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