EHJ：高选择性盐皮质激素受体拮抗剂BAY 94-8862或更适用于心衰患者

　　一项多国联合研究表明，在伴中度慢性肾病的左室射血分数降低心衰（HFrEF）患者中，BAY 94-8862（5–10 mg/d）与螺内酯（25 或50 mg/d）疗效相当，但高钾血症和肾功能恶化发生率显著降低。论文于5月27日在线发表于《欧洲心脏杂志》（Eur Heart J）。

　　BAY 94-8862为高选择性强效非类固醇盐皮质激素受体拮抗剂（MRA）。此项随机、对照、II期试验由两部分组成。在第一部分中，评估65例伴轻度肾病的HFrEF患者口服BAY 94-8862[2.5、5、或10 mg 每日一次(q.d.)]的安全性和耐受性。在第二部分中，对比392例伴中度肾病的HFrEF患者应用BAY 94-8862（(2.5、5或10 mg q.d.，或5 mg 2次/天）与安慰剂和开放标签螺内酯（25 或50 mg/d）的效果。

　　结果显示，与螺内酯相比，BAY 94-8862与血钾浓度平均升高幅度显著降低，以及高钾血症和肾功能恶化发生率降低具有相关性。BAY 94-8862降低B型脑利钠肽（BNP）、n端proBNP和蛋白尿的幅度至少等同于螺内酯。BAY 94-8862相关性不良事件罕见并且大部分轻微。

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

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.