提示: 手机请竖屏浏览!

利伐沙班联用或不联用阿司匹林治疗稳定性心血管疾病
Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease


John W. Eikelboom ... 心脑血管疾病 • 2017.10.05
相关阅读
• 利伐沙班在近期发生急性冠脉综合征患者中的应用 • 患者服用直接作用的口服抗凝剂后发生GI出血的危险 • 哪种抗凝策略适用于新置入支架的心房颤动患者 • 利伐沙班和阿司匹林在预防复发性静脉血栓栓塞方面的比较 • 口服直接抗凝药所致出血中凝血酶原复合物浓缩物的应用

摘要


背景

本试验评价了在心血管疾病的二级预防中,单独应用利伐沙班或利伐沙班联合阿司匹林是否比单独应用阿司匹林更加有效。

 

方法

在这项双盲试验中,27,395例稳定性动脉粥样硬化性血管疾病患者被随机分为三组:联合用药组每日2次2.5 mg利伐沙班联合每日1次100 mg阿司匹林,利伐沙班单药组每日2次5 mg利伐沙班,阿司匹林单药组每日1次100 mg阿司匹林。主要结局是由心血管死亡、卒中或心肌梗死所构成的复合结局。由于联合用药组显示优效性,因而本试验在平均随访23个月后提前终止。

 

结果

与阿司匹林单药组相比,利伐沙班联合阿司匹林组显著减少了主要结局的发生,阿司匹林单药组和联合用药组的发生人数分别为496(5.4%)和379(4.1%)(风险比,0.76;95%置信区间[CI],0.66~0.86;P<0.001;z=-4.126),但利伐沙班联合阿司匹林组发生大出血事件的人数较多,阿司匹林单药组和联合用药组的发生人数分别为170(1.9%)和288(3.1%)(风险比,1.70;95% CI,1.40~2.05;P<0.001)。在颅内出血或致死性出血的发生率方面,两组并没有显著性差异。联合用药组中有313例死亡(死亡率为3.4%),阿司匹林单药组中有378例(4.1%)(风险比,0.82;95% CI,0.71~0.96;P=0.01,P值的显著性阈值为0.0025)。与阿司匹林单药组相比,利伐沙班单药组没有显著减少主要结局的发生人数,但是更多患者发生大出血事件。

 

结论

在稳定性动脉粥样硬化性血管疾病患者中,与单独应用阿司匹林相比,联合应用利伐沙班(2.5 mg,每日2次)比阿司匹林具有更好的心血管结局和更多的大出血事件。与单独应用阿司匹林相比,单独应用利伐沙班(5 mg,每日2次)并未改善心血管结局,且会发生更多大出血事件(由拜耳公司资助,COMPASS在ClinicalTrials.gov注册号为NCT01776424)。





作者信息

John W. Eikelboom, M.B., B.S., Stuart J. Connolly, M.D., Jackie Bosch, Ph.D., Gilles R. Dagenais, M.D., Robert G. Hart, M.D., Olga Shestakovska, M.Sc., Rafael Diaz, M.D., Marco Alings, Ph.D., Eva M. Lonn, M.D., Sonia S. Anand, M.D., Petr Widimsky, M.D., Masatsugu Hori, M.D., Alvaro Avezum, Ph.D., Leopoldo S. Piegas, M.D., Kelley R.H. Branch, M.D., Jeffrey Probstfield, M.D., Deepak L. Bhatt, M.D., Jun Zhu, M.D., Yan Liang, M.D., Aldo P. Maggioni, M.D., Patricio Lopez-Jaramillo, Ph.D., Martin O’Donnell, Ph.D., Ajay K. Kakkar, M.B., B.S., Keith A.A. Fox, M.B., Ch.B., Alexander N. Parkhomenko, Ph.D., Georg Ertl, M.D., Stefan Störk, M.D., Matyas Keltai, M.D., Lars Ryden, M.D., Nana Pogosova, Ph.D., Antonio L. Dans, M.D., Fernando Lanas, Ph.D., Patrick J. Commerford, M.B., Ch.B., Christian Torp-Pedersen, M.D., Tomek J. Guzik, Ph.D., Peter B. Verhamme, M.D., Dragos Vinereanu, Ph.D., Jae-Hyung Kim, Ph.D., Andrew M. Tonkin, M.D., Basil S. Lewis, M.D., Camilo Felix, M.D., Khalid Yusoff, M.B., B.S., P. Gabriel Steg, M.D., Kaj P. Metsarinne, Ph.D., Nancy Cook Bruns, M.D., Frank Misselwitz, M.D., Edmond Chen, M.D., Darryl Leong, M.B., B.S., and Salim Yusuf, D.Phil., for the COMPASS Investigators*
From the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON (J.W.E., S.J.C., J.B., R.G.H., O.S., E.M.L., S.S.A., D.L., S.Y.), and Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC (G.R.D.) — both in Canada; Estudios Clínicos Latino América and Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Amphia Ziekenhuis and Werkgroep Cardiologische Centra Nederland (WCN), Utrecht, the Netherlands (M.A.); Cardiocenter, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic (P.W.); Osaka International Cancer Institute, Osaka, Japan (M.H.); Instituto Dante Pazzanese de Cardiologia (A.A.), and Hospital do Coração (L.S.P.), São Paulo; University of Washington Medical Center (K.R.H.B.) and University of Washington (J.P.), Seattle; Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston (D.L.B.); FuWai Hospital, Beijing (J.Z., Y.L.); National Association of Hospital Cardiologists Research Center (ANMCO), Florence, Italy (A.P.M.); Research Institute, Fundación Oftalmológica de Santander (FOSCAL)–Bucaramanga, Bucaramanga, Colombia (P.L.-J.); National University of Ireland, Galway (M.O.); Thrombosis Research Institute and University College London, London (A.K.K.), Centre for Cardiovascular Science, University of Edinburgh, Edinburgh (K.A.A.F.), and University of Glasgow, Glasgow (T.J.G.) — all in the United Kingdom; Collegium Medicum Jagiellonian University, Krakow, Poland (T.J.G); Institute of Cardiology, Kiev, Ukraine (A.N.P.); University of Würzburg and University Hospital, Würzburg (G.E., S.S.), and Bayer, Leverkusen (N.C.B., F.M., E.C.) — all in Germany; Semmelweis University, Budapest, Hungary (M.K.); Karolinska Institutet, Stockholm (L.R.); National Research Center for Preventative Medicine, Moscow (N.P.); University of Philippines, Manila (A.L.D.); Universidad de La Frontera, Temuco, Chile (F.L.); University of Cape Town, Cape Town, South Africa (P.J.C.); University of Aalborg, Copenhagen (C.T.-P.); University of Leuven, Leuven, Belgium (P.B.V.); University of Medicine and Pharmacology, Carol Davila University and Emergency Hospital, Bucharest, Romania (D.V.); Catholic University of Korea, Seoul, South Korea (J.-H.K.); Monash University, Melbourne, VIC, Australia (A.M.T.); Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.); Facultad de Ciencias de la Salud Eugenio Espejo–Universidad Tecnológica Equinoccial, Quito, Ecuador (C.F.); Universiti Teknologi Mara, Selangor, Malaysia (K.Y.); Université Paris Diderot, Hôpital Bichat, Assistance Publique–Hôpitaux de Paris, Paris (P.G.S.); and Turku University Central Hospital and Turku University, Turku, Finland (K.P.M.). Address reprint requests to Dr. Eikelboom at the Population Health Research Institute, McMaster University and Hamilton Health Sciences, David Braley Research Bldg., Hamilton General Hospital, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at eikelbj@mcmaster.ca. *A complete list of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA 2010;304:1350-1357

2. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860

3. Anand SS, Yusuf S. Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 2003;41:Suppl S:62S-69S

4. Turpie AG, Lassen MR, Eriksson BI, et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty: pooled analysis of four studies. Thromb Haemost 2011;105:444-453

5. The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-1297

6. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510

7. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891

8. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9-19

9. Bosch J, Eikelboom JW, Connolly SJ, et al. Rationale, design and baseline characteristics of participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. Can J Cardiol 2017;33:1027-1035

10. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692-694

11. Brechenmacher T, Xu J, Dmitrienko A, Tamhane AC. A mixture gatekeeping procedure based on the Hommel test for clinical trial applications. J Biopharm Stat 2011;21:748-767

12. Connolly SJ, Eikelboom JW, Bosch J, et al. Randomized trial of rivaroxaban in stable coronary artery disease. Lancet (in press).

13. Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban in patients with stable peripheral or carotid artery disease: an international randomized, double-blind, placebo-controlled trial. Lancet (in press).

14. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 2007;357:217-227

15. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-1339

16. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-1717

17. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-1800

18. Hiatt WR, Fowkes FGR, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. N Engl J Med 2017;376:32-40

19. Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012;366:1404-1413

服务条款 | 隐私政策 | 联系我们