Rivaroxaban with or without aspirin in patients with stable coronary artery disease

an international, randomised, double-blind, placebo-controlled trial

COMPASS investigators

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)205-218
Number of pages14
JournalThe Lancet
Volume391
Issue number10117
DOIs
Publication statusPublished - 20-01-2018

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Aspirin
Coronary Artery Disease
Placebos
Hemorrhage
Rivaroxaban
Myocardial Infarction
Mortality
Therapeutics
Morbidity
Stable Angina
Peripheral Arterial Disease
Unstable Angina
Platelet Activation
Percutaneous Coronary Intervention
Random Allocation
Coronary Artery Bypass
Blood Vessels
Outpatients
Research Personnel

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

@article{e3f3e3db2cd94b8e9231511b37072eb9,
title = "Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial",
abstract = "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.",
author = "{COMPASS investigators} and Connolly, {Stuart J.} and Eikelboom, {John W.} and Jackie Bosch and Gilles Dagenais and Leanne Dyal and Fernando Lanas and Kaj Metsarinne and Martin O'Donnell and Dans, {Anthony L.} and Ha, {Jong Won} and Parkhomenko, {Alexandr N.} and Avezum, {Alvaro A.} and Eva Lonn and Liu Lisheng and Christian Torp-Pedersen and Petr Widimsky and Maggioni, {Aldo P.} and Camilo Felix and Katalin Keltai and Masatsugu Hori and Khalid Yusoff and Guzik, {Tomasz J.} and Bhatt, {Deepak L.} and Branch, {Kelley R.H.} and {Cook Bruns}, Nancy and Berkowitz, {Scott D.} and Anand, {Sonia S.} and Varigos, {John D.} and Fox, {Keith A.A.} and Salim Yusuf and JORGELINA SALA and CARTASEGNA, {L. U.I.S.} and MARISA VICO and HOMINAL, {MIGUEL ANGEL} and EDUARDO HASBANI and ALBERTO CACCAVO and CESAR ZAIDMAN and DANIEL VOGEL and ADRIAN HRABAR and SCHYGIEL, {PABLO OMAR} and CARLOS CUNEO and LUQUEZ, {H. U.G.O.} and MACKINNON, {IGNACIO J.} and {AHUAD GUERRERO}, {RODOLFO ANDRES} and COSTABEL, {JUAN PABLO} and BARTOLACCI, {INES PALMIRA} and OSCAR MONTANA and MARIA BARBIERI and {GOMEZ VILAMAJO}, OSCAR and Yukio Ozaki",
year = "2018",
month = "1",
day = "20",
doi = "10.1016/S0140-6736(17)32458-3",
language = "English",
volume = "391",
pages = "205--218",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10117",

}

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

In: The Lancet, Vol. 391, No. 10117, 20.01.2018, p. 205-218.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rivaroxaban with or without aspirin in patients with stable coronary artery disease

T2 - an international, randomised, double-blind, placebo-controlled trial

AU - COMPASS investigators

AU - Connolly, Stuart J.

AU - Eikelboom, John W.

AU - Bosch, Jackie

AU - Dagenais, Gilles

AU - Dyal, Leanne

AU - Lanas, Fernando

AU - Metsarinne, Kaj

AU - O'Donnell, Martin

AU - Dans, Anthony L.

AU - Ha, Jong Won

AU - Parkhomenko, Alexandr N.

AU - Avezum, Alvaro A.

AU - Lonn, Eva

AU - Lisheng, Liu

AU - Torp-Pedersen, Christian

AU - Widimsky, Petr

AU - Maggioni, Aldo P.

AU - Felix, Camilo

AU - Keltai, Katalin

AU - Hori, Masatsugu

AU - Yusoff, Khalid

AU - Guzik, Tomasz J.

AU - Bhatt, Deepak L.

AU - Branch, Kelley R.H.

AU - Cook Bruns, Nancy

AU - Berkowitz, Scott D.

AU - Anand, Sonia S.

AU - Varigos, John D.

AU - Fox, Keith A.A.

AU - Yusuf, Salim

AU - SALA, JORGELINA

AU - CARTASEGNA, L. U.I.S.

AU - VICO, MARISA

AU - HOMINAL, MIGUEL ANGEL

AU - HASBANI, EDUARDO

AU - CACCAVO, ALBERTO

AU - ZAIDMAN, CESAR

AU - VOGEL, DANIEL

AU - HRABAR, ADRIAN

AU - SCHYGIEL, PABLO OMAR

AU - CUNEO, CARLOS

AU - LUQUEZ, H. U.G.O.

AU - MACKINNON, IGNACIO J.

AU - AHUAD GUERRERO, RODOLFO ANDRES

AU - COSTABEL, JUAN PABLO

AU - BARTOLACCI, INES PALMIRA

AU - MONTANA, OSCAR

AU - BARBIERI, MARIA

AU - GOMEZ VILAMAJO, OSCAR

AU - Ozaki, Yukio

PY - 2018/1/20

Y1 - 2018/1/20

N2 - 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.

AB - 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.

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U2 - 10.1016/S0140-6736(17)32458-3

DO - 10.1016/S0140-6736(17)32458-3

M3 - Article

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SP - 205

EP - 218

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10117

ER -