BY LIZETTE BORRELI
Aspirin is recommended for the prevention of new cardiovascular events for patients with atherosclerosis. However, its efficacy in reducing the risk for myocardial infarction (MI), stroke, or vascular death varies. Now in a new study, researchers found that combining anticoagulant and antiplatelet therapy may be better than either alone for stroke prevention.
Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS), a randomized, double-blind, parallel trial published on February 26 in Circulation found patients with coronary artery or peripheral artery disease, treated with a combination of rivaroxaban plus aspirin—2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily—compared with aspirin alone—experienced a 42 percent reduction in all-cause stroke.
The COMPASS trial, first published in 2017 in the New England Journal of Medicine, focused on the combined rate of cardiovascular death, myocardial infarction, or stroke during an average of 23 months of follow-up. The trial was designed to run up to four years, but it was stopped early after an overwhelming benefit of the combination therapy.
The combination of rivaroxaban 2.5 mg twice daily plus aspirin reduced the rate of cardiovascular death, stroke, or MI by 1.3 percent; patients experienced a 1.2 percent increase in bleeding.
Now, in a secondary analysis, the researchers, led by Mike Sharma, MD, a stroke neurologist in the Population Health Research Institute of McMaster University in Hamilton, Ontario, Canada, focused on the efficacy of rivaroxaban plus aspirin on various measures of stroke among patients with stable coronary artery or peripheral artery disease.
The team drew data from the COMPASS trial, which enrolled 27,395 patients, average age 68 years, with stable coronary or peripheral artery disease at 602 centers in 33 countries.
Participants were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152).
The researchers excluded patients who required anticoagulation or had a stroke within one month, previous lacunar stroke, or intracerebral hemorrhage.
During an average 23 months of follow-up, patients in the rivaroxaban plus aspirin group had fewer strokes, compared with those taking aspirin only—83, or 0.9 percent per year versus 142, or 1.6 percent per year, respectively (p<0.0001).
Compared with the aspirin only group, the annualized rate of ischemic/uncertain stroke among patients assigned the combination of rivaroxaban plus aspirin was reduced by almost half: 68, or 0.7 percent per year versus 132, or 1.4 percent per year, respectively (p<0.0001).
No significant differences were found in strokes in the rivaroxaban alone group compared with aspirin.
There were fewer fatal and disabling strokes, defined by a modified Rankin Scale score between 3– 6, in the aspirin plus rivaroxaban group than in the aspirin group only group (p=0.01).
Prior stroke was found to be the strongest predictor of incident stroke (p<0.0001), which was associated with a 3.4 percent per year rate of stroke recurrence with aspirin.
Overall, the researchers concluded "low-dose rivaroxaban plus aspirin is an important new option for efficacious antithrombotic therapy for primary and especially secondary prevention of stroke in patients with atherosclerosis."
They added that the risk reduction for secondary prevention is significant and makes a "compelling case favoring the use of 2.5 mg rivaroxaban twice daily plus aspirin in these patients."
Study limitations included the exclusion of participants with recent stroke, thus, limiting the generalizability of these findings during the early poststroke period. Moreover, the researchers did not systematically collect transient ischemic attacks from sites, opening up the possibility for misclassification of some strokes as transient ischemic attacks. Lastly, imaging for suspected stroke was done at the site and not reviewed centrally.
Dr. Sharma reported grants and personal fees from Bayer, Bristol-Myers Squibb, Daiichi Sankyo, and Portola. Study co-authors reported several conflicts of interest relevant to the study.
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Sharma M, Hart RG, Connolly SJ, et al. Stroke Outcomes in the COMPASS Trial. Circulation2019 Feb 26;139(9):1134-1145.