NEJM:华法林与阿司匹林在心脏射血分数降低患者中的疗效比较

　　背景  对于窦性心律的心力衰竭患者，尚不了解华法林或阿司匹林治疗是否较好。

　　方法  我们设计了这项试验以确定对于左室射血分数（LVEF）降低的窦性心律患者，华法林（目标国际标准化比为2.0~3.5）或阿司匹林（剂量为325 mg/d）是否为一种较好的治疗。我们随访2305例患者长达6年[均值±标准差（SD），3.5±1.8]。主要转归为至缺血性卒中、颅内出血或任何原因所致死亡的复合终点中首例事件的时间。

　　结果  华法林组主要转归发生率为7.47 例事件/100 患者-年，阿司匹林组为7.93 例事件/100 患者-年[华法林的风险比为0.93，95%可信区间（CI）0.79~1.10，P=0.40]。因此，两种治疗间没有显著的总体差异。在时变分析中，风险比随时间推移而变化，到随访第4年时华法林稍微优于阿司匹林，但这一结果仅具有临界显著性（P=0.046）。与阿司匹林相比，华法林与整个随访期内缺血性卒中发生率显著降低（0.72例事件/100患者-年对1.36 例事件/100 患者-年，风险比为0.52，95%CI 0.33~0.82，P=0.005）相关。华法林组严重出血发生率为1.78 例事件/100患者-年，相比之下阿司匹林组为0.87 例事件/100 患者- 年（P＜0.001）。两个治疗组间大脑内和颅内出血发生率无显著差异（华法林组为0.27例事件/100患者-年，阿司匹林组为0.22 例事件/100患者-年，P=0.82）。

　　结论  在LVEF 降低的窦性心律患者中，用华法林治疗和用阿司匹林治疗在主要转归方面没有显著的总体差异。华法林治疗使缺血性卒中危险的降低被严重出血危险升高所抵消。华法林和阿司匹林之间的选择应个体化。

Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm

BACKGROUND

It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.

METHODS

We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause.

RESULTS

The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82).

CONCLUSIONS

Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.)