Harry S Truman VA Medical Center, Columbia, MO 65211, USA.
Expert Opin Investig Drugs. 2010 May;19(5):653-61. doi: 10.1517/13543781003781906.
The renin-angiotensin-aldosterone system (RAAS) is a key regulator of blood pressure (BP), as well as volume and electrolytes, in both hypertensive and normotensive individuals. Inappropriate activation of the RAAS is important in hypertension-induced cardiovascular disease (CVD) and chronic kidney disease (CKD). Renin is the rate-limiting step in the RAAS cascade, which makes direct renin inhibitors (DRIs) an attractive target for RAAS suppression and treatment of hypertension. Current regimens using either angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) result in feedback upregulation of renin and aldosterone breakthrough, which contribute to incomplete suppression of the RAAS. Thereby, aliskiren - alone or in combination - might offer a novel therapeutic intervention to improve suppression of the RAAS, with potential to translate to improved CVD and CKD outcomes.
Herein, we present the current state of knowledge of DRIs in the preclinical and clinical realm and their antihypertensive efficacy in relation to cardiovascular and renal risk. Recent clinical trials (2007 - 2009) support the efficacy of aliskiren, and studies suggest the potential for improved CVD and CKD outcomes.
An understanding of the mechanism of action of DRIs and a perspective of recent clinical trials.
The DRI aliskiren is an effective antihypertensive agent that preliminary data suggests has a beneficial effect in CVD and CKD. Combination of aliskiren with an ACEi or ARB may be better tolerated than the ACEi-ARB combination. Future work is needed to further quantify aliskiren's impact on hard CVD and CKD end points.
肾素-血管紧张素-醛固酮系统（RAAS）是血压（BP）以及高血压和正常血压个体的容量和电解质的关键调节剂。RAAS 的不适当激活在高血压引起的心血管疾病（CVD）和慢性肾病（CKD）中很重要。肾素是 RAAS 级联反应中的限速步骤，这使得直接肾素抑制剂（DRI）成为抑制 RAAS 和治疗高血压的有吸引力的目标。目前使用血管紧张素转换酶抑制剂（ACEi）或血管紧张素受体阻滞剂（ARB）的方案导致肾素和醛固酮突破的反馈上调，这导致 RAAS 抑制不完全。因此，阿利克仑 - 单独或联合使用 - 可能提供一种新的治疗干预措施，以改善 RAAS 的抑制作用，有可能改善 CVD 和 CKD 结局。
本文介绍了 DRI 在临床前和临床领域的现有知识状态及其与心血管和肾脏风险相关的降压疗效。最近的临床试验（2007-2009 年）支持阿利克仑的疗效，研究表明对 CVD 和 CKD 结局有改善的潜力。
对 DRI 作用机制的理解和对最近临床试验的看法。
DRI 阿利克仑是一种有效的抗高血压药物，初步数据表明对 CVD 和 CKD 有有益的影响。与 ACEi-ARB 联合使用阿利克仑可能比 ACEi-ARB 联合使用更能耐受。需要进一步的工作来进一步量化阿利克仑对硬 CVD 和 CKD 终点的影响。
