Segal J B, McNamara R L, Miller M R, Powe N R, Goodman S N, Robinson K A, Bass E B
Johns Hopkins University, General Internal Medicine, 1830 E. Monument St. 8th Floor, Baltimore, Maryland 21205, USA.
Cochrane Database Syst Rev. 2007 Jul 18;2006(3):CD001938. doi: 10.1002/14651858.CD001938.pub2.
Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use.
To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF.
Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999.
Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease.
Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug.
Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention {aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]}, with moderate evidence of more major bleeding { OR= 1.90 [95% C.I. 0.89,4.04].}. Aspirin was inconclusively more efficacious than placebo for stroke prevention {OR=0.68 [95% C.I. 0.29,1.57]}, with inconclusive evidence regarding more major bleeds {OR=0.81[95% C.I. 0.37,1.78]}. For primary prevention, assuming a baseline risk of 45 strokes per 1000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin {aggregate OR=0.64[95% C.I. 0.43,0.96]}, with only suggestive evidence for more major hemorrhage {OR =1.58 [95% C.I. 0.76,3.27]}. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin.
AUTHORS' CONCLUSIONS: The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.
心房颤动（AF）具有较高的中风及其他血栓栓塞事件风险。在房颤患者中合理使用药物预防血栓栓塞，需要比较患者的中风风险与药物使用导致出血的风险。
量化使用已在房颤中经过严格评估用于预防血栓栓塞的药物后中风、大出血及死亡的风险。
通过Cochrane协作网的CENTRAL数据库和MEDLINE检索文章，截至1999年12月。
纳入针对非术后房颤成年患者预防血栓栓塞药物的随机对照试验。排除风湿性瓣膜病患者的随机对照试验。
由两名评价员提取数据。对所有定性相似研究的比值比进行合并，并根据研究规模加权，得出每种药物中风、大出血及死亡的汇总比值比。
本综述纳入14篇文章。华法林在预防首次中风方面比安慰剂更有效{中风的汇总比值比（OR）=0.30[95%置信区间（C.I.）0.19,0.48]}，有中等证据表明大出血更多{OR = 1.90[95% C.I. 0.89,4.04]}。阿司匹林在预防中风方面比安慰剂更有效的证据不明确{OR=0.68[95% C.I. 0.29,1.57]}，关于大出血更多的证据也不明确{OR=0.81[95% C.I. 0.37,1.78]}。对于一级预防，假设每1000患者年中风的基线风险为45次，华法林可以预防30次中风，代价是仅增加6次大出血。阿司匹林可以预防17次中风，且不增加大出血。直接比较显示，有中等证据表明服用华法林的患者中风次数少于服用阿司匹林者{汇总OR=0.64[95% C.I. 0.43,0.96]}，仅有提示性证据表明大出血更多{OR =1.58 [95% C.I. 0.76,3.27]}。然而在平均年龄65岁的较年轻患者中与阿司匹林相比，华法林导致的中风率绝对降低幅度较低（每1000人年5.5次），而在年龄较大组中为（每1000人年15次）。低剂量华法林或低剂量华法林联合阿司匹林在预防中风方面不如调整剂量的华法林有效。
证据有力支持在中风风险平均或更高的房颤患者中使用华法林，尽管显然存在出血风险。虽然证据未明确支持，但阿司匹林可能对中风风险较低的亚组预防中风有用，且出血风险低于华法林。需要对低分子量肝素和阿司匹林在低风险患者中做进一步研究。
