By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York-Presbyterian/Weill Cornell Medical College
Dr. Fink Reports no financial relationships relevant to this field of study.
SOURCE: Sharma M, Hart RG, Smith EE, et al. Rivaroxiban for prevention of covert brain infarcts and cognitive decline: The COMPASS MRI substudy. Stroke 2020;51:2901-2909.
Covert brain infarcts are detected on magnetic resonance imaging (MRI) studies in the aging brain in about 10% of people at age 65 years, increasing to 25% at age 80 years. They are more common than symptomatic ischemic stroke and are associated with the long-term development of cognitive decline, gait impairments, and behavioral disorders. Covert vascular lesions include white matter hyperintensities and cerebral microbleeds. They accumulate over time and are additive to changes that occur with amyloid deposition in Alzheimer’s disease. Most patients who develop dementia have a combination of multiple small infarcts, plus amyloid deposition. Prevention of covert infarcts is a strategy to mitigate the frequency and severity of late-life dementia.
Sharma et al evaluated a subset of patients who underwent brain MRIs in the COMPASS study. This study included patients who had stable coronary or peripheral artery disease, including carotid artery stenosis, who were randomized to aspirin 100 mg daily, or rivaroxiban 5 mg twice daily or 2.5 mg twice daily plus aspirin. The study showed a significant benefit for the combination of rivaroxiban and aspirin for the composite endpoint of stroke, myocardial infarction, or vascular death.1 Patients who underwent serial brain MRIs were evaluated for changes in covert infarcts during the course of the study. Baseline and follow-up imaging of the brain was completed in 1,445 participants over an interval of two years. Participants also had measurements of cognition and function. The primary endpoint was a proportion of participants with incident covert infarcts. Secondary endpoints were a composite of clinical stroke, covert infarcts, cerebral microbleeds, and white matter hyperintensities. At baseline, 493 (34.1%) participants had infarcts on imaging. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial, rivaroxiban plus aspirin reduced clinical ischemic stroke by 49%. In the substudy looking at covert infarcts, the effects of rivaroxiban plus aspirin vs. aspirin alone were 2.4% vs. 3.5% respectively, a non-statistically significant difference. Incident microbleeds occurred in 6.6% of participants, and 65.7% of the participants had an increase in white matter hyperintensities over time with no effect of treatment for any endpoint. There was no effect on cognitive testing as well. In conclusion, treatment with rivaroxiban and aspirin did not reduce the development of covert infarcts but did have a beneficial effect in reducing the risk of clinical ischemic stroke.
- Eikelboom JW, Connolly, SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319-1330.