Abstract
Until recently, attempts to improve the benefit of aspirin by adding another antithrombotic agent have not resulted in a mortality reduction in patients with chronic symptomatic atherosclerosis. In this population, COMPASS is the only one among six trials to show a significant mortality reduction, thereby providing evidence of a clear net clinical benefit with the combination of low-dose rivaroxaban plus aspirin. In this systematic review, we sought to determine whether the mortality benefit of the combination arm in COMPASS is best explained by greater statistical power or by a more favorable efficacy–safety profile than the other regimens evaluated in patients with chronic symptomatic atherosclerosis.
Author contributions
K Shyamkumar, J Hirsh, VC Bhagirath, S Sinha, K Xu, JS Ginsberg, JW Eikelboom and NC Chan contributed to the conception and design of the study. S Sinha developed the search strategy. K Shyamkumar, K Xu and S Sinha performed the literature searches and extracted the data. K Shyamkumar and K Xu performed the quality assessment. K Shyamkumar, J Hirsh, S Sinha and NC Chan developed the initial analysis plan. K Shyamkumar, S Sinha and NC Chan performed the analyses. All authors contributed to the interpretation of the results. K Shyamkumar, J Hirsh and NC Chan wrote the initial draft and subsequent iterations. All authors critically revised the drafts for important intellectual content to produce the final manuscript.
Financial & competing interests disclosure
VC Bhagirath received an unrestricted educational grant from Pfizer Canada and honoraria from Bayer during the creation of this work. S Sinha received educational grants from the British Society of Haematology and Thrombosis UK during the creation of this work, as well as an educational grant from Chugai-Pharma outside the submitted work. R Díaz received grants from Bayer during the creation of this work and has received honoraria from Sanofi and Astra-Zeneca. JW Eikelboom is the recipient of a midcareer award from the Heart and Stroke Foundation and holds the Jack Hirsh/Population Health Research Institute Chair in Thrombosis and Atherosclerosis. JW Eikelboom has also received honoraria and research support from Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb/Pfizer, Daiichi Sankyo, Janssen, Portola and Sanofi Aventis. NC Chan holds a McMaster University Department of Medicine Internal Career Research Award and has received honoraria from Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.