Gullapalli Nageshwara, Bloch Michael J, Basile Jan
Department of Internal Medicine (111), University of Nevada-Reno, 1000 Locust Street, VAMC-Reno, NV 89503, USA.
Ther Adv Cardiovasc Dis. 2010 Dec;4(6):359-73. doi: 10.1177/1753944710384430. Epub 2010 Oct 21.
Agents that block the renin-angiotensin-aldosterone system (RAAS) are the cornerstones of antihypertensive therapy in patients at high risk for cardiovascular or renal disease. Recently, it was shown that activation of RAAS may occur through alternate pathways not inhibited by angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs), and that ACEIs, ARBs, or MRAs may actually cause a reactive increase in plasma renin concentration and activity. While these agents, alone or in combination, decrease blood pressure and cardiovascular events to varying degrees, the direct renin inhibitor is a new class of RAAS blocking agent. Aliskiren is the first US Food and Drug Administration-approved direct renin inhibitor with good oral bioavailability. ASPIRE HIGHER is an ongoing series of clinical trials designed to investigate the effect of aliskiren on cardiovascular/renal surrogate endpoints and morbidity/mortality in patients with hypertension and high risk for cardiovascular or renal disease.
对于心血管疾病或肾脏疾病高危患者，阻断肾素-血管紧张素-醛固酮系统（RAAS）的药物是抗高血压治疗的基石。最近有研究表明，RAAS的激活可能通过不受血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）或盐皮质激素受体拮抗剂（MRA）抑制的替代途径发生，并且ACEI、ARB或MRA实际上可能导致血浆肾素浓度和活性的反应性增加。虽然这些药物单独或联合使用可不同程度地降低血压和心血管事件，但直接肾素抑制剂是一类新型的RAAS阻断剂。阿利吉仑是首个获得美国食品药品监督管理局批准的、具有良好口服生物利用度的直接肾素抑制剂。“追求更高目标”（ASPIRE HIGHER）是一系列正在进行的临床试验，旨在研究阿利吉仑对高血压且有心血管或肾脏疾病高风险患者的心血管/肾脏替代终点以及发病率/死亡率的影响。
