University of Michigan, Ann Arbor, MI, USA.
Eur J Heart Fail. 2011 Jul;13(7):755-64. doi: 10.1093/eurjhf/hfr034. Epub 2011 Apr 4.
We evaluated the influence of concomitant mineralocorticoid receptor antagonists (MRAs) on the safety and neurohumoral effects of a direct renin inhibitor in the ALiskiren Observation of Heart Failure Treatment (ALOFT) study.
Patients with stable New York Heart Association class II-IV heart failure (HF), plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL, and treated with an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker) and β-blocker were randomized to once-daily, double-blind treatment with aliskiren 150 mg or placebo, added to optimal HF therapy, for 12 weeks. Safety, tolerability, and effects of aliskiren on neurohumoral biomarkers were assessed in patients who received (MRA+) and did not receive (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n = 52; placebo, n = 49). Mineralocorticoid receptor antagonist status did not affect the ability of aliskiren 150 mg, added to standard HF therapy, to lower BNP, N-terminal proBNP, plasma renin activity, and urinary aldosterone. For example, the end-of-study to baseline ratio of geometric mean for BNP was: MRA+ group: aliskiren 0.68 [95% confidence interval (CI) 0.47, 0.98], placebo 0.85 (0.58, 1.24); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P= 0.720. The incidence of pre-specified adverse events (renal dysfunction, symptomatic hypotension, and hyperkalaemia) was low, and there were no significant differences between aliskiren and placebo in either MRA subgroup.
Aliskiren 150 mg added to standard HF therapy was well tolerated over 12 weeks and provided beneficial changes in neurohumoral biomarkers regardless of concomitant MRA treatment.
我们评估了伴随使用盐皮质激素受体拮抗剂（MRA）对直接肾素抑制剂在阿利克仑观察心力衰竭治疗（ALOFT）研究中的安全性和神经激素影响。
稳定的纽约心脏协会（NYHA）心功能 II-IV 级心力衰竭（HF）患者，血浆 B 型利钠肽（BNP）浓度>100pg/ml，且正在接受血管紧张素转换酶抑制剂（或血管紧张素受体阻滞剂）和β受体阻滞剂治疗，被随机分为每日一次、双盲治疗，接受阿利克仑 150mg 或安慰剂治疗，同时加用最佳 HF 治疗，为期 12 周。评估了接受（MRA+）和未接受（MRA-）基线时 MRA 治疗的患者的安全性、耐受性和阿利克仑对神经激素生物标志物的影响。在 302 名随机患者中，有 101 名患者正在接受 MRA 治疗（阿利克仑，n=52；安慰剂，n=49）。MRA 状态并不影响阿利克仑 150mg 联合标准 HF 治疗降低 BNP、N 末端 proBNP、血浆肾素活性和尿醛固酮的能力。例如，研究结束时与基线的 BNP 几何均数比值为：MRA+组：阿利克仑 0.68[95%置信区间（CI）0.47，0.98]，安慰剂 0.85（0.58，1.24）；MRA-组：阿利克仑 0.62（0.45，0.84），安慰剂 0.85（0.63，1.15），交互 P=0.720。预先指定的不良事件（肾功能障碍、症状性低血压和高钾血症）发生率较低，阿利克仑和安慰剂在 MRA 亚组之间无显著差异。
阿利克仑 150mg 联合标准 HF 治疗 12 周耐受性良好，无论是否伴随 MRA 治疗，均可对神经激素生物标志物产生有益变化。
