British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Cardiovasc Drugs Ther. 2011 Aug;25(4):315-21. doi: 10.1007/s10557-011-6319-3.
To compare the effect of the direct renin inhibitor aliskiren on neurohumoral activity in heart failure patients treated with low-dose and high-dose ACE inhibitor.
A retrospective analysis of the ALOFT trial. Comparison of the effects of 6 months treatment with aliskiren (versus placebo) in patients receiving <guideline-recommended dose of ACE inhibitor (n = 109) with those receiving ≥ recommended-dose (n = 81). Neurohumoral measures included B-type natriuretic peptide (BNP), NT proBNP, plasma renin activity and urinary aldosterone excretion.
Patients in each ACE inhibitor-dose group were generally similar (those in the ≥ recommended ACE inhibitor-dose had higher baseline blood-pressures and LVEF and were more often female and diabetic). In the <recommended-dose sub-group, the reduction in BNP from baseline to end-of-study was -1% (95% CI -32 to +44%) in the placebo-group and -32% (-1 to -53%) in the aliskiren group. The corresponding reductions in the ≥recommended ACE inhibitor-dose sub-group were: placebo -19% (-46 to +22%) and aliskiren -46% (-22 to -62%); interaction p-value 0.94. The pattern of results for other neurohumoral markers was similar.
Aliskiren causes neurohumoral suppression in heart failure, even in patients treated with ≥recommended-dose of ACE inhibitor.
比较直接肾素抑制剂阿利吉仑对接受低剂量和高剂量 ACE 抑制剂治疗的心衰患者神经激素活性的影响。
对 ALOFT 试验进行回顾性分析。比较 6 个月阿利吉仑（与安慰剂相比）治疗接受<指南推荐剂量 ACE 抑制剂（n=109）患者与接受≥推荐剂量 ACE 抑制剂（n=81）患者的效果。神经激素测量包括 B 型利钠肽（BNP）、NT proBNP、血浆肾素活性和尿醛固酮排泄。
每个 ACE 抑制剂剂量组的患者通常相似（接受≥推荐剂量 ACE 抑制剂的患者基线血压和左心室射血分数更高，且更常为女性和糖尿病患者）。在<推荐剂量亚组中，安慰剂组从基线到研究结束时 BNP 降低 1%（95%CI -32 至 +44%），阿利吉仑组降低 32%（-1 至 -53%）。相应地，在≥推荐剂量 ACE 抑制剂亚组中，安慰剂组降低 19%（-46 至 +22%），阿利吉仑组降低 46%（-22 至 -62%）；交互 p 值为 0.94。其他神经激素标志物的结果模式相似。
即使在接受≥推荐剂量 ACE 抑制剂治疗的患者中，阿利吉仑也能引起心力衰竭的神经激素抑制。
