Fox Keith A A, Antman Elliott M, Montalescot Gilles, Agewall Stefan, SomaRaju Bhupathi, Verheugt Freek W A, Lopez-Sendon Jose, Hod Hanoch, Murphy Sabina A, Braunwald Eugene
University of Edinburgh, Edinburgh, United Kingdom.
J Am Coll Cardiol. 2007 Jun 12;49(23):2249-55. doi: 10.1016/j.jacc.2006.12.049. Epub 2007 May 25.
The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial provided the opportunity to evaluate the impact of renal dysfunction on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and compare enoxaparin (ENOX) and unfractionated heparin (UFH).
It is unclear how renal dysfunction influences the balance between benefit and risk of antithrombotic therapy.
In the ExTRACT-TIMI 25 trial, 20,479 patients were randomized to UFH or ENOX. A reduced ENOX dose was administered to patients age > or =75 years and those with an estimated creatinine clearance (CrCl) <30 ml/min.
A powerful relationship was observed between the severity of renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke, intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There was a progressive increase in the treatment benefit with ENOX on death or nonfatal myocardial infarction (p < 0.01) with better renal function. Net clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was significantly superior with ENOX (p < 0.001) for patients with a CrCl >60 ml/min (79.1% of the study population). Major bleeding and intracranial hemorrhage did not differ for patients with preserved renal function (CrCl >90 ml/min), but in those with renal dysfunction there was a progressively greater increase in the risk of major and minor bleeding with ENOX.
Enoxaparin was superior to UFH for the majority of subjects. With more severe renal dysfunction, the net clinical benefit between ENOX and UFH did not differ, despite the rise in adverse events in both treatment groups. Future studies should take renal dysfunction into account when assessing antithrombotic regimens.
ExTRACT-TIMI 25（依诺肝素与急性心肌梗死溶栓再灌注治疗-心肌梗死溶栓25）试验提供了一个机会，来评估肾功能不全对ST段抬高型心肌梗死（STEMI）患者预后的影响，并比较依诺肝素（ENOX）和普通肝素（UFH）。
尚不清楚肾功能不全如何影响抗栓治疗的获益与风险平衡。
在ExTRACT-TIMI 25试验中，20479例患者被随机分为接受UFH或ENOX治疗。年龄≥75岁及估计肌酐清除率（CrCl）<30 ml/min的患者给予降低剂量的ENOX。
观察到肾功能不全严重程度（CrCl每降低10 ml/min）与死亡、卒中、颅内出血以及严重和轻微出血之间存在密切关系（每项p<0.001）。肾功能越好，ENOX在死亡或非致死性心肌梗死方面的治疗获益逐渐增加（p<0.01）。对于CrCl>60 ml/min的患者（占研究人群的79.1%），ENOX的净临床获益（死亡、非致死性心肌梗死或非致死性严重出血）显著更优（p<0.001）。肾功能正常（CrCl>90 ml/min）的患者，严重出血和颅内出血无差异，但在肾功能不全的患者中，ENOX导致的严重和轻微出血风险增加得更多。
对于大多数受试者，依诺肝素优于普通肝素。肾功能不全越严重，尽管两个治疗组的不良事件均增加，但ENOX和UFH之间的净临床获益无差异。未来研究在评估抗栓方案时应考虑肾功能不全因素。
