NEJM：Apixaban延长治疗静脉血栓栓塞安全有效

阿哌沙班是一种特异性Xa因子抑制剂，其单一、固定剂量的治疗方案或为静脉血栓栓塞的延长治疗提供了选择。日前，意大利Perugia大学Agnelli博士等人的研究显示，2.5-mg剂量或5-mg剂量的阿哌沙班延长抗凝结治疗可减少静脉血栓栓塞的复发风险，且不引起主要出血事件发生率升高。论文发表于国际权威杂志NEJM 2012年12月14日 在线版上。

在一项随机、双盲研究中，研究人员比较了两种剂量（2.5 mg和5 mg，一天两次）的阿哌沙班与安慰剂治疗已完成6至12个月的抗凝治疗的静脉血栓栓塞患者的疗效，入组的持续或中止抗凝结治疗的患者有良好的临床平衡。药物治疗维持12个月。

结果显示，共有2486例患者接受随机分组治疗，其中482例患者被纳入意向治疗分析。研究人员发现，在安慰剂治疗组中的829例患者中有73例(8.8%)出现症状复发静脉血栓栓塞或死静脉血栓栓塞死亡，与之相比，2.5 mg阿哌沙班治疗组的840例患者和5 mg阿哌沙班治疗组813例患者中分别有14例(1.7%)（相差7.2个百分点；95% 置信区间[CI], 5.0 至9.30）和14例(1.7%)（相差7.2个百分点；95% 置信区间[CI], 5.0 至9.30）患者出现上述结局（两组均有P<0.001）。安慰剂治疗组大出血发生率为0.5%，相比之下，2.5-mg阿哌沙班治疗组为0.2%，5-mg阿哌沙班治疗组为0.1%。研究人员观察到，安慰剂治疗组临床有关的非主要出血事件的发生率为2.3%，2.5-mg阿哌沙班治疗组为3.0%，5-mg阿哌沙班治疗组为4.2%。安慰剂组因任何原因的死亡率为1.7%，与之相比，2.5-mg阿哌沙班治疗组为0.8%，5-mg阿哌沙班治疗组为0.5%。

研究人员由此得出结论，2.5-mg剂量或5-mg剂量的阿哌沙班延长抗凝结治疗可减少静脉血栓栓塞的复发风险，且不引起主要出血事件发生率升高。

DOI: 10.1056/NEJMoa1207541
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Apixaban for Extended Treatment of Venous Thromboembolism

Giancarlo Agnelli, M.D., Harry R. Buller, M.D., Ph.D., Alexander Cohen, M.D., Madelyn Curto, D.V.M., Alexander S. Gallus, M.D., Margot Johnson, M.D., Anthony Porcari, Ph.D., Pharm.D., Gary E. Raskob, Ph.D., and Jeffrey I. Weitz, M.D. for the AMPLIFY-EXT Investigators

BACKGROUND Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.)

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