Orlando， FL –根据第58届ACC会议上3月31日的报道，对于心血管疾病高危患者来讲，早期应用依替巴肽较PCI过程中延迟暂缓给药并无优势。会议报道了EARLY ACS研究（非ST抬高ACS患者早期应用糖蛋白IIb/IIIa受体拮抗剂的研究），旨在明确依替巴肽的最佳应用时间。对于心血管疾病高危患者依替巴肽的应用策略有两种：在入院即刻早期静脉内注射以及PCI过程中延迟注射。“因为在应用依替巴肽的时间和最佳用法的问题上，指南和实践存在着差距，促使我们开展本项研究，从该药首次应用至今，已广泛应用于现代治疗的很多领域，” 来自Duke 大学医学中心的药学副教授--L. Kristin Newby医学博士说，“关于依替巴肽以及类似药物的应用时间在北美和欧洲的指南推荐均有所改变，在不同的医院和不同的医生对该药的应用也有所不同。”

    EARLY ACS是一项随机、双盲、对照研究，比较早期应用依替巴肽和基于标准化抗血小板药物基础上临时在PCI过程中应用依替巴肽的效果。本研究共纳入9492例患者，所有患者在应用试验药物后12-96小时内均计划进行侵入性治疗。

    本研究的初级有效终点为最初96小时内全因死亡率，包括心肌梗死、需急诊血运重建的再发心肌缺血或者血栓形成。次级终点是30天内死亡或心肌梗死。安全性评估终点为出血、输血、卒中以及不良事件。

    在纳入结束之际，EARLY ACS研究表明早期应用依替巴肽有98%的把握度降低22.5%的96小时内初级复合终点发生率，有81%的把握度降低15%30天死亡以及心肌梗死发生率。

     “我们旨在确定什么事高危患者治疗的最佳策略，” 来自哈佛大学布莱根妇女医院的Robert P. Giugliano助理教授说，“在美国很多医院通常在患者入院时常规注射依替巴肽，然而也有一部分医生倾向于在导管介入治疗后根据情况应用该药物。在本研究之前，对于哪种方法更好尚不得知。根据目前的指南，这两种方法均是可以推荐的。”

    对所有高危患者早期应用依替巴肽其安全性并无优势，而且还发现出血发生率增高。

     “我们的研究虽然不能对依替巴肽的应用达到一锤定音的效果，但对其在高危患者中的最佳应用策略还是能够提供一定的信息，” Newby说，“总的来说，医生们倾向于在PCI之后根据情况给予延迟应用依替巴肽。”对于患者而言，来自于EARLY ACS初步研究结果提供了关键信息——早期常规应用依替巴肽并没有优势。

（张丽洁 吕树铮  首都医科大学附属北京安贞医院）

英文原文：
EARLY vs. DELAYED PROVISIONAL UTILIZATION OF ANTI-PLATELET DRUG
Insignificant Advantage to Early Eptifibatide Use in High-Risk Patients

Orlando， FL – In patients with high risk of heart attack， early utilization of eptifibatide is not superior to delayed， provisional use of eptifibatide during percutaneous coronary intervention (PCI)， according to research presented today at the American College of Cardiology‟s 58th annual scientific session. The EARLY ACS study (Early Glycoprotien IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes) aimed to clarify the best strategy for eptifibatide use， an antiplatelet drug therapy successfully implemented in clinical practice for 10 years. Two common strategies of eptifibatide utilization were examined in patients with high-risk of heart attack: early intravenous injection upon immediate arrival at the hospital， and delayed， provisional injection during PCI. “The drivers for our study are the gaps that exist in the practice guidelines for when and how best to use eptifibatide， an already tested and proven treatment， in the context of other modern therapies that have evolved since the drug was first introduced，” said L. Kristin Newby， M.D.， MHS， associate professor of medicine at Duke University Medical Center， Durham， N.C. “Guidelines in North America and Europe vary in their recommendations regarding early use vs. delayed provisional treatment with eptifibatide and drugs like it. Individual hospitals and individual clinicians in all regions apply these recommendations differently.”

EARLY ACS was a randomized， double-blind， controlled study of early eptifibatide vs. provisional eptifibatide during PCI with standard background antithrombin therapy. A total of 9492 patients were enrolled， all of whom were scheduled to undergo an invasive strategy 12 to 96 hours after starting the study drug.

The primary efficacy endpoint for EARLY ACS was composite all-cause death， myocardial infarction， recurrent ischemia requiring urgent revascularization or thrombotic bailout during the first 96 hours. The secondary endpoint was death or myocardial infarction through 30 days. Safety endpoints included bleeding， transfusions， stroke and serious adverse events.

At its final enrollment， EARLY ACS had a 98 percent power to detect a 22.5 percent reduction in the 96-hour primary composite with early eptifibatide vs. delayed， provisional eptifibatide and 81 percent power for a 15 percent reduction in 30-day death or myocardial infarction. 

 “We set out to determine what is the better strategy when it comes to the treatment of these high-risk patients，” said Robert P. Giugliano， M.D. assistant professor of medicine at the Brigham and Women‟s Hospital， Harvard， M.A. “Many hospitals in the United States routinely start a course of injectable eptifibatide early when a patient arrives at the hospital. However， there are other physicians who prefer to employ a „wait and see‟ approach with the drug until after catheterization. Prior to this study， it was not clear which strategy was better. And， according to current practice guidelines， either strategy would be supported.”

For neither efficacy endpoint was the strategy of early eptifibatide use in all high-risk patients better than the delayed， provisional use of eptifibatide prior to PCI. Furthermore， early eptifibatide initiation was associated with more bleeding.
 “Our study， although not the final word regarding eptifibatide， has helped shed a light on how to best use eptifibatide among high-risk patients，” Newby said. “In general， physicians can feel comfortable with a strategy of delayed， provisional administration after a decision to proceed to PCI is made.” As far as patients are concerned， the primary results from EARLY ACS are the key message – an early routine strategy of eptifibatide is not superior to a delayed provisional strategy.”