Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

Publication ,  Journal Article
Connolly, SJ; Eikelboom, JW; Bosch, J; Dagenais, G; Dyal, L; Lanas, F; Metsarinne, K; O'Donnell, M; Dans, AL; Ha, J-W; Parkhomenko, AN ...
Published in: Lancet
January 20, 2018

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Lancet

DOI

EISSN

1474-547X

Publication Date

January 20, 2018

Volume

391

Issue

10117

Start / End Page

205 / 218

Location

England

Related Subject Headings

  • Stroke
  • Rivaroxaban
  • Platelet Aggregation Inhibitors
  • Myocardial Infarction
  • Morbidity
  • Male
  • Humans
  • Hemorrhage
  • General & Internal Medicine
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Connolly, S. J., Eikelboom, J. W., Bosch, J., Dagenais, G., Dyal, L., Lanas, F., … COMPASS investigators, . (2018). Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet, 391(10117), 205–218. https://doi.org/10.1016/S0140-6736(17)32458-3
Connolly, Stuart J., John W. Eikelboom, Jackie Bosch, Gilles Dagenais, Leanne Dyal, Fernando Lanas, Kaj Metsarinne, et al. “Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.Lancet 391, no. 10117 (January 20, 2018): 205–18. https://doi.org/10.1016/S0140-6736(17)32458-3.
Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):205–18.
Connolly, Stuart J., et al. “Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.Lancet, vol. 391, no. 10117, Jan. 2018, pp. 205–18. Pubmed, doi:10.1016/S0140-6736(17)32458-3.
Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, Metsarinne K, O’Donnell M, Dans AL, Ha J-W, Parkhomenko AN, Avezum AA, Lonn E, Lisheng L, Torp-Pedersen C, Widimsky P, Maggioni AP, Felix C, Keltai K, Hori M, Yusoff K, Guzik TJ, Bhatt DL, Branch KRH, Cook Bruns N, Berkowitz SD, Anand SS, Varigos JD, Fox KAA, Yusuf S, COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):205–218.
Journal cover image

Published In

Lancet

DOI

EISSN

1474-547X

Publication Date

January 20, 2018

Volume

391

Issue

10117

Start / End Page

205 / 218

Location

England

Related Subject Headings

  • Stroke
  • Rivaroxaban
  • Platelet Aggregation Inhibitors
  • Myocardial Infarction
  • Morbidity
  • Male
  • Humans
  • Hemorrhage
  • General & Internal Medicine
  • Female