Akpan Anani, Mercer University College of Pharmacy
Xarelto® (rivaroxaban) is an oral anticoagulant with indications for the treatment and prevention of thromboses, but not for the secondary prevention of cardiovascular events.  Conversely, aspirin has been shown to lower the risk of major adverse cardiovascular events and even cardiovascular death compared to placebo.  As a result, low dose aspirin (≤100 mg) is recommended for all tolerant patients in need of secondary prevention.  Due to bleeding risks, anticoagulants have not been recommended for these same patients. 
|Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease |
|Design||A double-blind, double-dummy, randomized trial using a 3-by-2 partial factorial design; N= 27,395|
|Objective||To assess whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention|
|Study Groups||Rivaroxaban + Aspirin; n= 9,152
Rivaroxaban alone n= 9,117
Aspirin alone; n= 9,126
|Methods||The Cardiovascular Outcomes for People Using Anticoagulation
Strategies (COMPASS) trial was conducted in 602 centers in 33 countries.
Patients were eligible if they provided written informed consent and met the criteria for coronary artery disease, peripheral arterial disease, or both.
Participants were randomly assigned in a 1:1:1 ratio to receive
· rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily)
· rivaroxaban (5 mg twice daily) with an aspirin-matched placebo once daily
· aspirin (100 mg once daily) with a rivaroxaban matched placebo twice daily
After randomization, participants were seen at 1 and 6 months and then at 6-month intervals.
|Duration||March 2013 through May 2016|
|Primary Outcome Measure||A composite of cardiovascular death, stroke, or myocardial infarction|
|Adverse Events||Common Adverse Events:
R + A = 838 (9.2)
R alone = 741 (8.1)
Aspirin alone = 503 (5.5)
|Serious Adverse Events:
|Percentage Discontinued due to Adverse Events: N/A|
|Study Author Conclusions||Rivaroxaban plus aspirin had better cardiovascular outcomes than those assigned to aspirin alone; however, rivaroxaban alone did not result in better cardiovascular outcomes than aspirin alone.|
A notable limitation of this study is that it was stopped early for efficacy, potentially leading to an overestimation of the treatment effect. Additionally, the rigor of pre-trial secondary prevention therapy (i.e. the intensity of statins being taken, the doses/frequencies of NSAIDS, etc.) was not accounted for. However, the homogenous baseline characteristics support the conclusion that the combination therapy intervention did cause the statistically significant benefit observed.
 Xarelto® (rivaroxaban) tablets [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc.; Mar 2017.
 Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet 2009;373:1849-1860
 Hobbs FD. Cardiovascular disease: different strategies for primary and secondary prevention?. Heart. 2004;90(10):1217-23.
 Anand SS, Yusuf S. Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 2003;41:Suppl S:62S-69S
 Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017.