Heart Failure Efficacy Survival Study)入选了6642例AMI患者,旨在比较在常规使用ACE抑制剂和β受体阻滞剂的基础上,加用依普利酮25~50mg qd和安慰剂的效果[15]。与OPTIMAAL和VALIANT研究的入选标准类似,EPHESUS研究入选的同样是伴LVSD以及有急性心力衰竭临床和(或)影像学证据的AMI患者。结果表明,依普利酮可降低死亡率达15%(P=0.008),因心血管原因死亡或住院的复合终点减少13%(P=0.002)。这一结果强烈提示对于高危AMI患者,应在ACE抑制剂或ARB的基础上加用依普利酮。由于醛固酮可以独立调节血管紧张素Ⅱ的释放,并且ACE抑制剂长期应用后可能出现“醛固酮逃逸”,对于CHF患者而言,在ACE抑制剂或ARB基础上加用依普利酮,从药理学角度看亦有价值[16]。总之,醛固酮拮抗剂是高危AMI患者治疗的有益补充而非竞争性治疗。值得警惕的是,当醛固酮拮抗剂联合应用ACE抑制剂或ARB时,应注意监测血钾,避免高钾血症的发生。 4 结论 对于伴LVSD和(或)急性心力衰竭的高危AMI患者,ARB联合ACE抑制剂治疗可以使此类患者更大获益。ARB的验证剂量和ACE抑制剂的验证剂量并不等效。但联合治疗方案确实为临床医生提供了进一步阻断RAS、挽救生命的额外工具。缺点是足量的ARB可以导致更多的低血压、高血肌酐、高血钾出现。虽然对这些不良事件的监测将导致医疗费用上涨,但ARB带来的良好预后可以弥补这一不足。综合最近的大规模临床试验的结果,我们不难得出结论,ARB在减少高危AMI患者死亡、挽救生命方面的治疗地位日趋稳固。而醛固酮拮抗剂依普利酮的研究结果亦令人鼓舞。相信随着未来研究的进一步深入,在抑制高危AMI患者RAS激活方面,我们会有更多、更有效的方法来进行选择。 【参考文献】 1 Dickstein K,Kjekshus J.Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomized.Lancet,2002,360:752-760. 2 Pfeffer MA,Braunwald E,Moye LA,et al.Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction.Results of the survival and ventricular enlargement trial: the Save investigators.N Engl J Med,1992,327:669-667. 3 Yusuf S,Pfeffer MA,Swedberg K,et al.Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction:The CHARMPreserved Trial.Lancet,2003,362:777-781. 4 McAlpine HM,Morton JJ,Leckie B,et al.Neuroendocrine activation after acute myocardial infarction.Br Heart J,1988,60:117-124. 5 Rouleau JL,De Champlain J,Klein M,et al.Activation of neurohumoral systems in postinfarction left ventricular dysfunction.J Am Coll Cardiol,1993,22:390-398. 6 VJ Dzau,WS Colucci,NK Holleerg,et al.Relation of the reninangiotensinaldosterone system to clina state in congestive heart failure.Circulation,1981,63:645-651. 7 Urata H,Healy B,Stewart RW,et al.Angiotension Ⅱforming pathways in normal and failing human hearts.Cire Res,1990,66:883-890. 8 Petrie MC,Padmanabhan N,McDonald JE,et al.Angiotensin converting enzyme(ACE)and nonACE dependent angiotensin Ⅱ generation in resistance arteries from patients with heart failure and coronary heart disease.J Am Coll Cardial,2001,37:1056-1061. 9 Borghi C,Boschi S,Ambrosioni E,et al.Evidence of panml escape of renninangiotensinaldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors.J Clin Pharmacol,1993,33:40-45. 10 Lee AF,MacFadyen RJ,Struthers AD.Neurohormonal teactivation in heart failure patients on chronic ACE inhibitor therapy: a longitudinal study.Eur J Heart Fail,1999,1:401-406. 11 Cohn JN,Tognoni G.A randomized trial of the angiotensinreceptor blocker valsartan in chronic heart failure.N Engl J Med,2001,345:1667-1675. 12 Cohn JN,Anand IS,Latini R,et al.Sustained reouction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the valsartan Heart Failure Trial.Circulation,2003,108:1306-1309. 13 Cohn JN.Interaction of betablockrs and angiotensin receptor blockers/ACE inhibitors in heart failure.J Renin Angiotensin Aldosterone Syst,2003,4:137-139. 14 Yusuf S.From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis.Am J Cardiol,2002,89:18A-25A. 15 Pitt B,Remme W,Zannad F,et al.Eplerenone,a selective aldosterone blocker.in patients with left ventricular dysfunction after myocardial infarction.N Engl J M ed,2003,348:1309-1321. 16 Struthers AD.Aldosterone escape during andiotensinconverting enzyme inhibitor therapy in chronic heart failure.J Card Fail,1996,2:47-54. 上一页 [1] [2]
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