Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
Clin Cardiol. 2010 Sep;33(9):536-41. doi: 10.1002/clc.20828.
Renin-angiotensin aldosterone system (RAAS) activation is a key neurohormonal contributor to the progression of chronic heart failure. Strategies that block this activation have consistently demonstrated major beneficial impacts on morbidity and mortality in this setting. Direct renin inhibitors (DRIs) present a novel opportunity to block at an additional or alternative step in this pathway, that being conversion of angiotensinogen to angiotensin I. Theoretical benefits of blocking at the level of renin include: inhibition of the reflex activation of plasma renin activity induced by conventional downstream RAAS blockers. Minimization of angiotensin II and/or aldosterone escape and blocking upstream at the rate-limiting step of angiotensin I production. Preclinical and early-phase clinical studies have largely supported this hypothesis. In the Aliskiren Observation of Heart Failure Treatment study, patients with systolic chronic heart failure receiving background angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers and β-blockers benefited from aliskiren in reduction vs placebo of plasma levels of brain natriuretic peptide, the primary efficacy endpoint of that study. Large-scale outcome trials are, however, required to definitively determine the benefits of a DRI strategy additional to, or as an alternative to, conventional approaches such as ACE inhibitors in the systolic chronic heart failure setting. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.
肾素-血管紧张素-醛固酮系统（RAAS）的激活是慢性心力衰竭进展的关键神经激素因素。阻断这种激活的策略在这种情况下一致地显示出对发病率和死亡率的重大有益影响。直接肾素抑制剂（DRI）提供了一个阻断该途径中另外或替代步骤的新机会，即血管紧张素原转化为血管紧张素 I。在肾素水平阻断的理论益处包括：抑制由常规下游 RAAS 阻滞剂诱导的血浆肾素活性的反射激活。最小化血管紧张素 II 和/或醛固酮逃逸，并在血管紧张素 I 产生的限速步骤上阻断上游。临床前和早期临床研究在很大程度上支持了这一假说。在阿利克仑观察心力衰竭治疗研究中，接受背景血管紧张素转换酶（ACE）抑制剂或血管紧张素受体阻滞剂和β受体阻滞剂治疗的收缩性慢性心力衰竭患者，与安慰剂相比，阿利克仑降低了血浆脑钠肽水平，这是该研究的主要疗效终点。然而，需要进行大规模的结局试验，以明确确定 DRI 策略的益处，这种策略除了常规方法（如 ACE 抑制剂）之外，在收缩性慢性心力衰竭环境中作为替代方法。版权所有©2010 年 Wiley 期刊公司。作者没有资金、财务关系或利益冲突需要披露。
