Warfarin vs. Aspirin in Reduced Ejection Fraction (WARCEF)

描述(由申请人提供)：心力衰竭(HF)和低左室射血分数(EF)与中风和死亡的显著风险相关。然而，抗血栓/抗血小板治疗减少不良事件的价值仍然存在争议。华法林和阿司匹林最常在没有确切数据的情况下使用。慢性心力衰竭的抗血小板试验(WATCH)试图解决这个问题，但由于招募不佳而提前终止。华法林与阿司匹林在降低心脏射血分数试验中的对比试验(WARCEF)就是为了解决这个问题。这项随机、双盲、多中心临床试验的主要目的是确定华法林(INR 2.5-3.0；目标INR 2.75)或阿司匹林(每天325毫克)对左心室射血分数为35%的患者预防全因死亡率和中风(包括缺血性和出血性)的综合终点是更好的。主要的无效假设是，在EF&lt；/=35%的患者中，华法林和阿司匹林治疗在首次发生死亡或中风(缺血性和出血性)的时间上没有差异。这与这两个治疗之间的非零差异的替代假设进行了测试，在a=0.05的双侧，以检测17.82%的风险降低。首要的次要目标是回答华法林或阿司匹林在减少死亡、卒中、毫升和心力衰竭住院的联合终点方面哪一个更好。这一审判始于03/02年度。然而，研究进展缓慢，存在着各种各样的行政问题。在06/‘05年，S.Homma作为心脏科PI被引入，以监督临床操作。随后，所有地点的监管文件都得到遵守，并实施了定期安排的监测访问。严重的不良事件也被判定以确保患者的安全。还对组织结构进行了其他改革，以提高数据质量。为了在新的供资周期中提高组织效率，计划将受赠机构迁至哥伦比亚大学。(来自UMDNJ)，统计分析中心(J.L.T.Thompson，PI)也设在那里。目前，北美有74个中心正在招聘，欧洲有66个。目前，共有1242名患者入选(2006年8月1日)。根据现实的入院率，到08/11年度，患者总数预计为3,246人。随访期最短为1年，最长6年。然而，考虑到实际的事件发生率和治疗中断率，在所要求的资助期内，实现的功率可能低于80%。患者将需要额外随访12个月(超过5年)才能达到80%的疗效。随访期将从2年到6年不等。因此，如果有必要，我们计划在这个周期之后申请额外资金，以获得适当的电力。随着观察的结束，这项研究仍然是唯一一项评估低EF患者抗凝作用的研究，对越来越多的HF患者将如何治疗具有重大意义。

DESCRIPTION (provided by applicant): Heart failure (HF) and low left ventricular (LV) ejection fraction (EF) are associated with significant risk for stroke and death. However, the value of antithrombotic / antiplatelet therapy to reduce adverse events remains controversial. Warfarin and aspirin are most often used without definitive data. Antiplatelet Trial in Chronic Heart Failure (WATCH) attempted to address this issue, but was prematurely terminated due to poor recruitment. Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) is designed to address this issue. The primary aim of this randomized, double-blind, multi-center clinical trial is to determine whether warfarin (INR 2.5-3.0; target INR 2.75) or aspirin (325 mg per day) is superior for preventing the combined end point of all-cause mortality and stroke (both ischemic and hemorrhagic) in patients with LV EF<35%. The primary null hypothesis is that in patients with EF</=35%, there will be no difference between warfarin and aspirin therapies in time to the first occurrence of death or stroke (ischemic and hemorrhagic). This is tested against the alternative hypothesis of a non-zero difference between these two treatments, at a=.05 two-sided, to detect a 17.82% hazard rate reduction. The top secondary aim is to answer if warfarin or aspirin is superior for reducing combined endpoint of death, stroke, Ml, and HF hospitalization. This trial started in 03/'02. However, study progress was slow and a variety of administrative problems existed. In 06/'05, S. Homma was brought in as a Cardiology PI to oversee the clinical operations. Subsequently, regulatory documents from all sites were brought to compliance and regularly scheduled monitoring visits implemented. Serious adverse events were also adjudicated to assure patient safety. Other changes in organizational structure were implemented to increase data quality. To increase organizational efficiency in the new funding cycle, the grantee institution is planned to be moved to Columbia Univ. (from UMDNJ), where Statistical Analysis Center (J.L.T. Thompson, PI) is also located. Currently, 74 centers in North America, and 66 in Europe are recruiting. At this time, 1,242 patients are enrolled (8/01/'06). Based on the REALISTIC enrollment rate, the total patient number by 08/'11 is expected to be 3,246. Minimum follow up period is 1 year and maximum 6 years. However, given the actual event rates and interruption of therapy rate, the achieved power is likely to be under 80% within the requested funding period. Patients will need be followed for 12 additional months (beyond the end of 5-years) to achieve >80% power. Follow up period will then range from 2 to 6 years. As such, if necessary, we plan to request additional funding after this cycle to obtain appropriate power. With ending of WATCH, this study remains the only study assessing the role of anticoagulation in patients with low EF, with major implications for how the growing number of HF patients will be treated.