From the Internal Vascular and Emergency Medicine-Stroke Unit, University of Perugia, Perugia (G.A., C.B., M.V.), Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) Research Center, Milan (G.G.), the Department of Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara (M.C.), the Department of Medicine, Buon Consiglio-Fatebenefratelli Hospital, Naples (A.F.), and Internal Medicine, Azienda Ospedale-Università, Padua (G.V.) - all in Italy; Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, and INNOVTE, Saint-Etienne (G.M.) - both in France; Instituto de Investigatión Sanitaria Gregorio Marañon, Universidad Complûtense, Madrid (A.M.); the Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (M.V.H.); the Hematology Division, Brigham and Women's Hospital, and Harvard Medical School, Boston (J.M.C.); Guy's and St. Thomas' NHS Foundation Trust Hospital, King's College London, London (A.C.); the Department of Vascular Medicine, Darmstadt, and Center for Thrombosis and Hemostasis, University of Mainz, Mainz (R.B.) - both in Germany; the Institute of Hematology and Bone Marrow Transplantation Unit, Rambam Health Care Campus Technion, Israel Institute of Technology, Haifa (B.B.); the Departments of Pulmonary Circulation, Thromboembolic Diseases, and Cardiology, Center for Postgraduate Medical Education, Europejskie Centrum Zdrowia, Otwock, Poland (A.T.); the Surgical Oncology Department, Institut Português de Oncologia do Porto, Porto, Portugal (M.R.S.); and Cliniques Universitaires Saint-Luc, Brussels (C.L.).
N Engl J Med. 2020 Apr 23;382(17):1599-1607. doi: 10.1056/NEJMoa1915103. Epub 2020 Mar 29.
Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use.
This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding.
Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60).
Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).
最近的指南建议考虑使用口服依度沙班或利伐沙班治疗癌症患者的静脉血栓栓塞症。然而，这些口服药物的益处受到与使用相关的出血风险增加的限制。
这是一项多中心、随机、研究者发起的、开放标签、非劣效性临床试验，采用中心结局盲法评估。我们连续随机分配患有症状性或偶发性急性近端深静脉血栓形成或肺栓塞的癌症患者，接受口服阿哌沙班（前 7 天每天两次 10 毫克，随后每天两次 5 毫克）或皮下达肝素（前一个月每天一次 200 国际单位/千克体重，随后每天一次 150 国际单位/千克体重）。治疗持续 6 个月。主要终点是试验期间客观确认的复发性静脉血栓栓塞。主要安全性终点是大出血。
阿哌沙班组 576 例患者中有 32 例（5.6%）发生复发性静脉血栓栓塞，达肝素组 579 例患者中有 46 例（7.9%）（风险比，0.63；95%置信区间[CI]，0.37 至 1.07；非劣效性 P<0.001）。阿哌沙班组有 22 例（3.8%）患者发生大出血，达肝素组有 23 例（4.0%）患者发生大出血（风险比，0.82；95%CI，0.40 至 1.69；P=0.60）。
与皮下达肝素相比，口服阿哌沙班治疗癌症相关静脉血栓栓塞症不增加大出血风险，且非劣效。（由 Bristol-Myers Squibb-Pfizer 联盟资助；Caravaggio ClinicalTrials.gov 编号，NCT03045406。）
