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内科患者应用阿哌沙班和依诺肝素预防血栓形成的比较
Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients


Samuel Z. Goldhaber ... 心脑血管疾病 • 2011.12.08
相关阅读
• 阿哌沙班用于癌症患者的血栓预防 • 骑跨型与非骑跨型肺栓塞患者的院内死亡率相似

摘要


背景

许多内科患者出院后,会继续用药来预防静脉血栓栓塞,但此种做法的疗效和安全性一直未能确定。我们假定延长使用阿哌沙班是安全的,并且比使用依诺肝素短期预防更为有效。

 

方法

在这个双盲、双模拟、安慰剂对照试验中,入选的急症患者为充血性心力衰竭或呼吸衰竭,或其他内科疾病并至少伴有一项额外静脉血栓栓塞的危险因素,而且所有的入选者均预计住院治疗至少3天。这些患者被随机分成阿哌沙班和依诺肝素两组,前者口服阿哌沙班,剂量为2.5mg,每天2次,连续30天;后者皮下注射依诺肝素,剂量为40mg,每天1次,连续使用614天。主要疗效结局是用药30天的复合终点,包括静脉血栓栓塞相关死亡、肺栓塞、有症状的深静脉血栓形成或无症状的腿部近端深静脉血栓形成,后者的发现需要在第30天进行系统性双侧加压超声检查。主要的安全结局是出血。全部疗效和安全性结局均独立裁定。

 

结果

6,528名受试者经历了随机分组,其中4,495名能够评估主要疗效结局——阿哌沙班组2,211名,依诺肝素组2,284名。在可评估的这些患者中,阿哌沙班组和依诺肝素组分别有2.71%60名)和3.06%70名)达到主要疗效结局(阿哌沙班的相对危险是0.8795%可信区间[CI]0.621.23P=0.44)。到第30天时,阿哌沙班组发生大出血的比率是0.47%15/3,184),而依诺肝素组是0.19%6/3,217)(相对危险2.5895% CI1.027.24P=0.04)。

 

结论

有内科疾病患者在预防血栓时,延长阿哌沙班的服药时间并不比短期应用依诺肝素更具优势。两者比较,阿哌沙班与大出血事件的相关性显著多于依诺肝素(试验由百时美施贵宝[Bristol-Myers Squibb]和辉瑞公司[Pfizer]资助;ClinicalTrials.gov注册号为NCT00457002)。





作者信息

Samuel Z. Goldhaber, M.D., Alain Leizorovicz, M.D., Ajay K. Kakkar, M.D., Ph.D., Sylvia K. Haas, M.D., Ph.D., Geno Merli, M.D., Robert M. Knabb, Ph.D., and Jeffrey I. Weitz, M.D., for the ADOPT Trial Investigators*
From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (S.Z.G.); Unité de Pharmacologie Clinique, Université Claude Bernard Lyon I, Lyon, France (A.L.); Thrombosis Research Institute and University College London — both in London (A.K.K.); Institute for Experimental Oncology and Therapy Research, Technical University of Munich, Munich, Germany (S.K.H.); Jefferson Medical College, Thomas Jefferson University Hospitals, Philadelphia (G.M.); Bristol-Myers Squibb, Princeton, NJ (R.M.K.); and the Thrombosis and Atherosclerosis Research Institute and McMaster University — both in Hamilton, ON, Canada (J.I.W.). Address reprint requests to Dr. Goldhaber at Brigham and Women's Hospital, Cardiovascular Division, 75 Francis St., Boston, MA 02115, or at sgoldhaber@partners.org. *A complete list of the members and investigators in the Apixaban Dosing to Optimize Protection from Thrombosis (ADOPT) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386-1389

2. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988;318:1162-1173

3. Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999;341:793-800

4. Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874-879

5. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325-329

6. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;372:31-39

7. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S

8. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010;153:8-18

9. Rivaroxaban compares favorably with enoxaparin in preventing venous thromboembolism in acutely ill patients without showing a net clinical benefit. Washington, DC: American College of Cardiology, April 5, 2011 (http://www.cardiosource.org/News-Media/Media-Center/News-Releases/2011/04/MAGELLAN.aspx).

10. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010;363:2487-2498

11. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010;375:807-815

12. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-817

13. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992

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