WARCEF

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 2.1主要目标 WARCEF是一项双臂(1：1)双盲随机多中心临床试验。它的主要目的是比较华法林和阿司匹林治疗心力衰竭患者的有效性，同时考虑出血的风险。 主要的无效假设是，在EF为35%的患者中，华法林(INR 2.5-3.0，目标INR为2.75)与阿司匹林(325 mg/d)治疗在首次发生缺血性中风、脑出血(ICH)或死亡的时间上没有差异。这是根据这两种疗法之间的非零差异的替代假设进行测试的，在a=0.05的双侧，80%的功率检测到17.82%的风险降低(在适当考虑交叉和丢失后续治疗之后)，具有对称的停止和决策规则。3201例患者，随访2~6年。 这三种可能的结果中的任何一种都将具有临床重要性： +如果华法林效果更好，将推荐使用华法林。 +如果阿司匹林更好，建议使用阿司匹林。 +如果证据不足以证明这两种药物中的任何一种更好，则建议使用阿司匹林，因为它的成本更低，更容易给药。 因此，如果WARCEF以令人满意的力量完成，预计将在临床上起决定性作用。 2.2次要目标 1主要的次要目标是检验华法林和阿司匹林治疗在首次发生缺血性中风、脑出血、心肌梗死(MI)、心力衰竭(HF)住院或死亡的时间上没有差异的假设。 附加的次要目标是回答以下问题： 华法林和阿司匹林在减少中风(缺血性和出血性)方面哪个更好？ 3在女性中，华法林或阿司匹林治疗在减少缺血性中风、脑出血、心肌梗死、心力衰竭住院或死亡方面是更好的？ 4在非裔美国人中，华法林或阿司匹林疗法在减少缺血性中风、脑出血、心肌梗死、心力衰竭住院或死亡方面哪个更好？ 华法林或阿司匹林对中风、短暂性脑缺血发作(TIA)或外周血栓的相对风险或益处取决于射血分数吗？ 华法林或阿司匹林的相对风险或益处是否取决于心力衰竭分级(NYHA分级)？ 华法林或阿司匹林的相对风险或益处取决于病因吗？ 心力衰竭的症状？ 8华法林和阿司匹林对认知功能的影响有区别吗？ 与其他卒中亚型相比，华法林在心源性栓塞症中是否比阿司匹林有更大的风险降低？ 10非缺血性心脏病患者比缺血性心脏病患者更容易发生心源性梗塞吗？ 11心脏栓塞性梗死在女性中是否比男性更常见？ EF20%的患者的平均脑梗塞体积是否大于EF20%的患者？ 2.3第三个目标是将WARCEF的数据与华法林抗血小板试验在慢性心力衰竭(WATCH)中的数据结合起来，以提供更多的统计能力来解决第二个目标1至7。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 2.1 The Primary Aim WARCEF is a two-arm (1:1) double-blind randomized multicenter clinical trial. Its primary aim is to compare the effectiveness of warfarin and aspirin therapies in heart failure patients, while taking account of risk of hemorrhage. The primary null hypothesis is that in patients with EF ¿ 35%, there is no difference between warfarin (INR 2.5-3.0 with a target INR of 2.75) and aspirin (325 mg/day) therapies in time to the first to occur of ischemic stroke, intracerebral hemorrhage (ICH), or death. This is tested against the alternative hypothesis of a non-zero difference between these two therapies, at a = .05 two- sided, with power of 80% to detect a 17.82% hazard rate reduction (after appropriate allowance for crossover and loss to follow-up), with symmetrical stopping and decision rules. 3201 patients with 2-6 years of follow-up are required. Any of the three possible outcomes will be clinically important: + If warfarin is better, use of warfarin will be recommended. + If aspirin is better, use of aspirin will be recommended. + If the evidence is insufficient to declare either better, use of aspirin will be recommended, given its lower cost and easier administration. WARCEF is thus expected to be clinically decisive if it is completed with satisfactory power. 2.2 The Secondary Aims 1 The main secondary aim is to test the hypothesis of no difference in warfarin and aspirin therapies in time to the first to occur of, ischemic stroke, ICH, myocardial infarction (MI), heart failure (HF) hospitalization, or death. The additional secondary aims are to answer these questions: 2 Is warfarin or aspirin superior for reducing stroke (ischemic and hemorrhagic)? 3 Among women, is warfarin or aspirin therapy superior for reducing ischemic stroke, ICH, MI, heart failure hospitalization, or death? 4 Among African-Americans, is warfarin or aspirin therapy superior for reducing ischemic stroke, ICH, MI, heart failure hospitalization or death? 5 Does any relative risk or benefit of warfarin or aspirin for stroke, transient ischemic attack (TIA), or peripheral embolism depend on ejection fraction? 6 Does any relative risk or benefit of warfarin or aspirin depend on heart failure class (NYHA class)? 7 Does any relative risk or benefit of warfarin or aspirin depend on etiology of cardiac failure? 8 Do warfarin and aspirin differ in their effect on cognitive function? 9 Does warfarin have a larger risk reduction relative to aspirin in cardioembolic than other stroke subtypes? 10 Are cardioembolic infarcts more frequent in patients with non-ischemic than ischemic cardiac disease? 11 Are cardioembolic infarcts more frequent in women than in men? 12 Is mean cerebral infarct volume greater in patients with EF ¿ 20% than in patients with EF 20%? 2.3 The Tertiary aim is to combine the WARCEF data with that of the Warfarin Antiplatelet Trial in Chronic Heart Failure (WATCH) to provide more statistical power to address the secondary aims 1 through 7.