CCRE Therapeutics, Monash University, Melbourne, Australia.
Circ Heart Fail. 2013 Jul;6(4):711-8. doi: 10.1161/CIRCHEARTFAILURE.112.000173. Epub 2013 Apr 26.
In EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), eplerenone significantly reduced major cardiovascular events versus placebo in 2737 patients with mild symptoms of heart failure and an ejection fraction of <35%, in addition to recommended therapy. However, it is not known whether such benefits were preserved in patients receiving optimal background drug therapy, that is, high doses of angiotensin-converting enzyme inhibitor (ACEi, or angiotensin receptor blocker), β-blocker, or both drug classes.
We further analyzed EMPHASIS-HF according to the use and dose of these background drug classes. Patients receiving ≥ 50% of target dose were considered to be receiving high doses; patients on <50% or no drug comprised the low-dose group. The primary end point of the study (cardiovascular death/heart failure hospitalization), as well as all-cause mortality, was evaluated in this way. The beneficial clinical effects of eplerenone (as observed in the main study) were preserved for the EMPHASIS-HF primary end point in patients receiving higher doses of ACEi or angiotensin receptor blocker, β-blocker, or both (hazard ratio for eplerenone versus placebo, ACEi/angiotensin receptor blocker: high dose, 0.67; low dose, 0.65; β-blockers: high dose, 0.55; low dose, 0.72; both ACEi/angiotensin receptor blocker and β-blocker: high dose, 0.59; low dose, 0.68; P value for interaction 0.80, 0.15, and 0.53, respectively), as well as for all-cause mortality. There were no major safety issues, except a borderline increased risk of hypotension with eplerenone in those on high-dose ACEi or ACEi/β-blocker.
Eplerenone provides substantial benefit on major events (with an acceptable safety profile) in patients with mild symptoms of systolic heart failure, even in those already receiving high doses of standard background therapies.
在 EMPHASIS-HF（依普利酮在心力衰竭患者轻度住院和生存研究）中，依普利酮与安慰剂相比，在 2737 例有轻度心力衰竭症状和射血分数<35%的患者中，除了推荐的治疗方法外，还显著降低了主要心血管事件。然而，尚不清楚在接受最佳背景药物治疗的患者中，是否存在这种益处，即高剂量的血管紧张素转换酶抑制剂（ACEi，或血管紧张素受体阻滞剂）、β受体阻滞剂或这两类药物。
我们根据这些背景药物类别的使用和剂量进一步分析了 EMPHASIS-HF。接受≥50%目标剂量的患者被认为接受高剂量；接受<50%或无药物的患者为低剂量组。研究的主要终点（心血管死亡/心力衰竭住院）以及全因死亡率是以此方式评估的。依普利酮的有益临床效果（在主要研究中观察到）在接受更高剂量 ACEi 或血管紧张素受体阻滞剂、β受体阻滞剂或两者的患者中得到保留（依普利酮与安慰剂相比的风险比，ACEi/血管紧张素受体阻滞剂：高剂量，0.67；低剂量，0.65；β受体阻滞剂：高剂量，0.55；低剂量，0.72；ACEi/血管紧张素受体阻滞剂和β受体阻滞剂：高剂量，0.59；低剂量，0.68；交互作用 P 值分别为 0.80、0.15 和 0.53），以及全因死亡率。除了依普利酮在接受高剂量 ACEi 或 ACEi/β受体阻滞剂的患者中血压略有升高的边缘风险外，没有出现重大安全问题。
依普利酮在心衰患者的轻度症状中提供了显著的获益（具有可接受的安全性），即使在已经接受标准背景治疗高剂量的患者中也是如此。
