van Walraven Carl, Hart Robert G, Singer Daniel E, Laupacis Andreas, Connolly Stuart, Petersen Palle, Koudstaal Peter J, Chang Yuchiao, Hellemons Beppie
Clinical Epidemiology Unit, Ottawa Health Research Institute, F-6, Ottawa Hospital, Civic Campus, 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9.
JAMA. 2002 Nov 20;288(19):2441-8. doi: 10.1001/jama.288.19.2441.
Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events.
To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin).
Pooled analysis of patient-level data from 6 published, randomized clinical trials.
A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants.
Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle.
Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started.
Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.
非瓣膜性心房颤动（AF）患者发生中风和其他血管事件的风险增加。
比较接受维生素K拮抗剂口服抗凝剂或乙酰水杨酸（阿司匹林）治疗的非瓣膜性AF患者发生血管事件和出血事件的风险。
对6项已发表的随机临床试验的患者水平数据进行汇总分析。
总共4052例AF患者被随机分配接受治疗剂量的口服抗凝剂或阿司匹林，伴或不伴低剂量口服抗凝剂。
缺血性和出血性中风、其他心血管事件、全因死亡和大出血事件。计算人年发病率以进行粗略比较。使用按研究分层的比例风险模型评估相对疗效。通过交互项探讨口服抗凝剂的相对效果因相关患者因素的变化。所有分析均采用意向性分析原则。
接受口服抗凝剂和阿司匹林治疗的患者在重要预后因素方面均衡。在口服抗凝剂与阿司匹林对任何结局的相对疗效方面，各试验之间无显著异质性。接受口服抗凝剂治疗的患者发生任何中风（每100患者年2.4次事件与4.5次事件；风险比[HR]，0.55；95%置信区间[CI]，0.43 - 0.71）、缺血性中风（HR，0.48；95%CI，0.37 - 0.63）或心血管事件（HR，0.71；95%CI，0.59 - 0.85）的可能性显著降低，但发生大出血的可能性更高（每100患者年2.2次事件与1.3次事件；HR，1.71；95%CI，1.21 - 2.41）。阵发性AF患者缺血性中风风险的降低相似（每100患者年1.5次事件与4.7次事件；HR，0.32；95%CI，0.16 - 0.61；P <.001）。用口服抗凝剂而非阿司匹林治疗1000例AF患者1年可预防23例缺血性中风，同时导致额外9例大出血。总体全因生存率无差异，但在开始治疗3年后，口服抗凝剂治疗的患者似乎有所改善。
与阿司匹林相比，口服抗凝剂可显著降低非瓣膜性慢性或阵发性AF患者发生所有中风、缺血性中风和心血管事件的风险，但适度增加大出血的绝对风险。获益与风险的平衡因患者亚组而异。
