Division of Cardiovascular & Diabetes Medicine, MailBox 2, Ninewells Hospital and Medical School, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK.
Nat Rev Cardiol. 2013 Mar;10(3):125-34. doi: 10.1038/nrcardio.2012.196. Epub 2013 Jan 15.
The renin-angiotensin-aldosterone system is a well-established therapeutic target in the treatment of heart failure (HF). Substantial advances have been made with existing agents--angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), and mineralocorticoid-receptor antagonists (MRAs)--and new data continue to emerge. The indication for the use of MRAs has been broadened to include potentially all patients who have HF with reduced ejection fraction (HFrEF), and ACE inhibitors might have a novel application in patients who are at risk of left ventricular dysfunction (those with aortic valvular disease or pacing-induced heart disease). ARBs have been shown to be a beneficial alternative to ACE inhibitors in HFrEF, but their value when added to ACE inhibitors has been questioned. Upstream, direct renin blockade with aliskiren is being pursued in two large trials of HF, despite the premature halting of a third study. A substantial, unmet need remains in patients who have HF with preserved ejection fraction (HFpEF). New data on spironolactone and LCZ696 (a combined ARB and neprilysin inhibitor) show promise for these patients. Results of the TOPCAT study of spironolactone in patients with HFpEF are awaited, and LCZ696 is now being tested in a large trial in patients with HFrEF.
肾素-血管紧张素-醛固酮系统是心力衰竭（HF）治疗中一个成熟的治疗靶点。现有的药物——血管紧张素转换酶（ACE）抑制剂、血管紧张素 II 受体阻滞剂（ARBs）和盐皮质激素受体拮抗剂（MRAs）——已经取得了很大的进展，新的数据仍在不断涌现。MRAs 的适应证已经扩大到包括所有射血分数降低的心力衰竭（HFrEF）患者，而 ACE 抑制剂可能在有左心室功能障碍风险的患者（主动脉瓣疾病或起搏诱导性心脏病患者）中有新的应用。ARBs 已被证明在 HFrEF 中是 ACE 抑制剂的有益替代品，但在添加 ACE 抑制剂时其价值仍存在争议。尽管第三项研究提前停止，但两种 HF 大型试验仍在研究直接肾素抑制剂阿利克仑。射血分数保留的心力衰竭（HFpEF）患者仍存在大量未满足的需求。螺内酯和 LCZ696（ARB 和 Neprilysin 抑制剂的组合）的新数据为这些患者带来了希望。螺内酯在 HFpEF 患者中的 TOPCAT 研究结果仍在等待，LCZ696 目前正在 HFrEF 患者的大型试验中进行测试。
