Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University/Alfred Hospital, Melbourne VIC 3004, Australia.
Eur J Heart Fail. 2011 Jan;13(1):107-14. doi: 10.1093/eurjhf/hfq212.
The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.
肾素-血管紧张素-醛固酮系统（RAAS）是心力衰竭（HF）管理的重要治疗靶点。然而，阻断该系统的常规药物会引起血浆肾素活性（PRA）的反射性增加，这可能导致 RAAS“逃逸”。已经开发出直接肾素抑制剂（DRI），可降低 PRA，从而可能提供更大的 RAAS 阻断。阿利克仑是第一种口服活性 DRI。与安慰剂相比，阿利克仑可降低 B 型利钠肽（BNP）的血浆水平。最小化心力衰竭患者结局的肾素抑制试验（ATMOSPHERE）的目的是评估阿利克仑和依那普利单药治疗以及阿利克仑/依那普利联合治疗对慢性收缩性 HF、NYHA 心功能 II-IV 级症状和升高的 BNP 血浆水平患者的心血管死亡和 HF 住院的影响。
能耐受至少 10mg 或等效依那普利的患者将进行开放标签导入期，接受依那普利，然后接受阿利克仑。大约 7000 名耐受此导入期的患者将被随机 1:1:1 分为阿利克仑单药治疗、依那普利单药治疗或联合治疗。ATMOSPHERE 的主要终点是：（i）阿利克仑/依那普利联合治疗是否优于依那普利单药治疗，以延迟首次发生心血管死亡或 HF 住院的时间；（ii）阿利克仑单药治疗是否优于或至少不劣于依那普利单药治疗在该终点上。
ATMOSPHERE 研究将明确确定 DRI 策略在慢性收缩性 HF 患者中的作用，该策略可作为传统 RAAS 阻断的附加或替代策略。
