Cleland J G, Erhardt L, Murray G, Hall A S, Ball S G
Medical Research Council Research Initiative in Heart Failure, University of Glasgow, Scotland, U.K.
Eur Heart J. 1997 Jan;18(1):41-51.
The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed.
The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation.
Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ramipril reduced the risk of sudden death by 30% (95% CI: 8-47%; P = 0.011). However, overall, 45% of those patients who died suddenly had severe or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure. Ramipril did not selectively alter the proportion of in- to out-of-hospital deaths.
Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.
血管紧张素转换酶（ACE）抑制剂对猝死、进行性心力衰竭和再梗死的影响在降低心力衰竭患者及心肌梗死后患者的总体死亡率方面的重要性存在争议。
AIRE研究将2006例在心肌梗死后2至9天内有临床或影像学证据表明存在心力衰竭的患者随机分为两组，分别接受每日两次5毫克雷米普利治疗或匹配的安慰剂治疗。终点由对治疗分配不知情的终点委员会成员独立评估。
与安慰剂相比，接受雷米普利治疗的患者中，作为首个经确认的终点发生严重顽固性心力衰竭的患者较少，尽管高危幸存者数量更多（分别为143例和178例；风险降低23%；可信区间为5%至39%；P = 0.017）。雷米普利未改变再梗死或中风的发生率。无论治疗分配如何，182例（46%）患者在死亡前发生了顽固性心力衰竭。76例（19%）患者在死亡前发生了经确认的急性或陈旧性心肌再梗死，90例（23%）患者在死亡前后出现胸痛，提示这些死亡存在缺血因素。80例患者在首次住院时死亡，167例在再次住院期间死亡，145例在院外死亡。猝死占所有死亡的54%，占院外死亡的93%。雷米普利使猝死风险降低了30%（95%可信区间：8%至47%；P = 0.011）。然而，总体而言，45%的猝死患者在死亡前患有严重或进行性心力衰竭。只有39%的猝死被认为是由心律失常所致。雷米普利使循环衰竭导致的死亡风险降低了18%，但未达到统计学意义（95%可信区间：-41%至14%；P = 0.237）。对猝死和循环衰竭导致的死亡的影响幅度无显著差异。然而，总体死亡率降低的38%来自于在死亡前已发生严重顽固性心力衰竭的猝死亚组（安慰剂组n = 35，雷米普利组n = 15），这再次强调了在预防心力衰竭方面的显著益处。雷米普利未选择性改变院内死亡与院外死亡的比例。
雷米普利可降低心肌梗死后早期有心力衰竭证据患者的死亡率，并减少进展为顽固性心力衰竭的情况。延缓心力衰竭的进展似乎是通过减少循环衰竭和减少猝死来降低死亡率的主要因素。
