Warfarin vs. Aspirin in Reduced Ejection Fraction (WARCEF)

描述（由申请人提供）：心力衰竭（HF）和低左心室射血分数（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被使用，但没有明确的数据。慢性心力衰竭抗血小板试验（WATCH）试图解决这一问题，但由于招募不良而过早终止。华法林与阿司匹林降低心脏射血分数试验（WARCEF）旨在解决这一问题。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（325 mg /天）在预防左室EF<35%的患者全因死亡率和卒中（缺血性和出血性）的联合终点方面是否更优。主要的零假设是，在EF</=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。这是针对这两种治疗之间非零差异的替代假设进行的测试，在双侧= 0.05时，检测到危险率降低了17.82%。最重要的次要目的是回答华法林或阿司匹林在减少死亡、卒中、Ml和HF住院的综合终点方面是否更优越。这项审判开始于03/ 02年。然而，研究进展缓慢，存在各种管理问题。在06/ 05年，S. Homma作为心脏病学PI来监督临床操作。随后，所有场址的规范性文件都得到遵守，并定期进行监测访问。严重的不良事件也被裁定，以确保患者的安全。对组织结构进行了其他更改，以提高数据质量。为了在新的资助周期中提高组织效率，受资助机构计划从UMDNJ转移到哥伦比亚大学，统计分析中心（J.L.T. Thompson， PI）也位于哥伦比亚大学。目前，北美有74家中心，欧洲有66家中心正在招聘。此时，1242名患者入组（2006年8月1日）。根据REALISTIC入组率，到2008 / 11年患者总数预计为3246人。随访时间最短1年，最长6年。然而，考虑到实际事件发生率和治疗中断率，在要求的资助期内，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年结束）以达到bbb80 %的功率。随访期为2至6年。因此，如有必要，我们计划在此周期后申请额外资金以获得适当的权力。随着WATCH的结束，这项研究仍然是唯一一项评估抗凝在低EF患者中的作用的研究，这对越来越多的HF患者将如何治疗具有重要意义。

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.