利伐沙班联合或不联合阿司匹林用于稳定型心血管疾病。

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

机构信息

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.).

出版信息

N Engl J Med. 2017 Oct 5;377(14):1319-1330. doi: 10.1056/NEJMoa1709118. Epub 2017 Aug 27.

DOI:10.1056/NEJMoa1709118

PMID:28844192

Abstract

BACKGROUND

We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.

METHODS

In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.

RESULTS

The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.

CONCLUSIONS

Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

摘要

背景

我们评估了利伐沙班单独或联合阿司匹林与阿司匹林单独相比，在二级心血管预防方面是否更有效。

方法

在这项双盲试验中，我们将 27395 名稳定的动脉粥样硬化性血管疾病患者随机分为三组，分别接受利伐沙班（每日 2 次，每次 2.5 毫克）加阿司匹林（每日 1 次，每次 100 毫克）、利伐沙班（每日 2 次，每次 5 毫克）或阿司匹林（每日 1 次，每次 100 毫克）治疗。主要终点是心血管死亡、卒中和心肌梗死的综合结果。在平均随访 23 个月后，由于利伐沙班加阿司匹林组的优越性，研究停止。

结果

与阿司匹林组相比，利伐沙班加阿司匹林组的主要终点事件患者更少（379 例[4.1%]比 496 例[5.4%]；风险比，0.76；95%置信区间[CI]，0.66 至 0.86；P<0.001；z=-4.126），但利伐沙班加阿司匹林组大出血事件患者更多（288 例[3.1%]比 170 例[1.9%]；风险比，1.70；95%CI，1.40 至 2.05；P<0.001）。两组间颅内或致命性出血无显著差异。利伐沙班加阿司匹林组有 313 例死亡（3.4%），而阿司匹林组有 378 例（4.1%）（风险比，0.82；95%CI，0.71 至 0.96；P=0.01；显著性阈值 P 值为 0.0025）。与阿司匹林组相比，利伐沙班组的主要终点事件发生率无显著降低，但大出血事件发生率更高。

结论

在稳定的动脉粥样硬化性血管疾病患者中，与阿司匹林单独治疗相比，每日 2 次 2.5 毫克利伐沙班加阿司匹林治疗可改善心血管结局并增加大出血事件；与阿司匹林单独治疗相比，每日 2 次 5 毫克利伐沙班治疗未改善心血管结局，但增加了大出血事件。（拜耳公司资助；COMPASS 临床试验。gov 编号，NCT01776424）。