Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism.

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Isabelle Mahé, Marc Carrier, Didier Mayeur, Jean Chidiac, Eric Vicaut, Nicolas Falvo, Olivier Sanchez, Claire Grange, Manuel Monreal, Juan J López-Núñez, Remedios Otero-Candelera, Grégoire Le Gal, Erik Yeo, Marc Righini, Helia Robert-Ebadi, Menno V Huisman, Frederikus A Klok, Peter Westerweel, Giancarlo Agnelli, Cecilia Becattini, Aristotelis Bamias, Kostas Syrigos, Sebastian Szmit, Adam Torbicki, Peter Verhamme, Anthony Maraveyas, Alexander T Cohen, Cihan Ay, Céline Chapelle, Guy Meyer, Francis Couturaud, Patrick Mismetti, Philippe Girard, Laurent Bertoletti, Silvy Laporte
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引用次数: 0

Abstract

Background: In patients with active cancer and venous thromboembolism, whether extended treatment with a reduced dose of an oral anticoagulant is effective in preventing recurrent thromboembolic events and decreasing bleeding is unclear.

Methods: We conducted a randomized, double-blind, noninferiority trial with blinded central outcome adjudication. Consecutive patients with active cancer and proximal deep-vein thrombosis or pulmonary embolism who had completed at least 6 months of anticoagulant therapy were randomly assigned in a 1:1 ratio to receive oral apixaban at a reduced (2.5 mg) or full (5.0 mg) dose twice daily for 12 months. The primary outcome was centrally adjudicated fatal or nonfatal recurrent venous thromboembolism, assessed in a noninferiority analysis (margin of 2.00 for the upper boundary of the 95% confidence interval of the subhazard ratio). The key secondary outcome was clinically relevant bleeding, assessed in a superiority analysis.

Results: A total of 1766 patients underwent randomization at a median time since the index event of 8.0 months (interquartile range, 6.5 to 12.6); 866 patients were assigned to the reduced-dose group, and 900 to the full-dose group. The median treatment duration was 11.8 months (interquartile range, 8.3 to 12.1). Recurrent venous thromboembolism occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 (cumulative incidence, 2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41; P = 0.001 for noninferiority). Clinically relevant bleeding occurred in 102 patients (cumulative incidence, 12.1%) in the reduced-dose group and in 136 (cumulative incidence, 15.6%) in the full-dose group (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P = 0.03). Mortality was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio, 0.96; 95% CI, 0.86 to 1.06).

Conclusions: Extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent venous thromboembolism in patients with active cancer. The reduced dose led to a lower incidence of clinically relevant bleeding complications than the full dose. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; API-CAT ClinicalTrials.gov number, NCT03692065.).

背景:对于患有活动性癌症和静脉血栓栓塞症的患者,减少口服抗凝剂剂量的延长治疗是否能有效预防复发性血栓栓塞事件并减少出血,目前尚不清楚:我们进行了一项随机、双盲、非劣效性试验,并进行了盲法中央结果判定。连续接受抗凝治疗至少 6 个月且患有活动性癌症和近端深静脉血栓或肺栓塞的患者按 1:1 的比例被随机分配到接受减量(2.5 毫克)或全量(5.0 毫克)阿哌沙班口服治疗,每天两次,为期 12 个月。主要结果是集中判定的致命性或非致命性复发性静脉血栓栓塞,通过非劣效性分析进行评估(亚危险比 95% 置信区间的上限为 2.00)。主要的次要结果是临床相关出血,在优劣分析中进行评估:共有1766名患者接受了随机化治疗,中位治疗时间为8.0个月(四分位间范围为6.5至12.6个月);866名患者被分配到减量组,900名患者被分配到全剂量组。中位治疗时间为 11.8 个月(四分位间范围为 8.3 至 12.1)。减量组有18名患者(累计发生率为2.1%)出现复发性静脉血栓栓塞,全剂量组有24名患者(累计发生率为2.8%)出现复发性静脉血栓栓塞(调整后次危险比为0.76;95%置信区间[CI]为0.41至1.41;非劣效性P=0.001)。减量组有102名患者发生临床相关出血(累计发生率为12.1%),全量组有136名患者发生临床相关出血(累计发生率为15.6%)(调整后次危险比为0.75;95% 置信区间[CI]为0.58至0.97;P = 0.03)。减量组的死亡率为17.7%,全剂量组为19.6%(调整后危险比为0.96;95% CI为0.86至1.06):在预防活动性癌症患者复发性静脉血栓栓塞方面,减量阿哌沙班延长抗凝治疗效果不优于全剂量阿哌沙班。与全剂量相比,减量阿哌沙班导致的临床相关出血并发症发生率更低。(由百时美施贵宝-辉瑞联盟资助;API-CAT ClinicalTrials.gov 编号:NCT03692065)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
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