Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment

Vijayakumar Javalkar, MD, MCh; Okkes Kuybu, MD; Abdallah Amireh, MD; Roger E. Kelley, MD


South Med J. 2020;113(11):585-592. 

In This Article

Lower-dose Rivaroxaban Plus Aspirin

In the COMPASS (Stroke Outcomes In The Cardiovascular Outcomes For People Using Anticoagulation Strategies) trial,[59] patients with stable CAD with or without peripheral vascular disease were randomly assigned to either aspirin 100 mg/day, rivaroxaban 5 mg twice daily, or rivaroxaban 2.5 mg twice daily plus aspirin. The combined low-dose rivaroxaban plus aspirin was associated with a lower stroke risk at 0.9%/year compared with 1.6%/year in the aspirin-only group (HR 0.58, 95% CI 0.44–0.76, P < 0.001).[60] Ischemic and uncertain strokes were reduced by nearly 50% (HR 0.51, 95% CI 0.38–0.68, P < 0.001), and no significant difference was seen in the rivaroxaban-alone versus aspirin-alone patients. In a subsequent secondary analysis,[61] there were significantly fewer cardioembolic strokes (HR 0.4, 95% CI 0.20–0.78, P = 0.005) and ESUSs (HR 0.30, 95% CI 0.12–0.74, P = 0.006) with combined rivaroxaban 2.5 mg twice daily plus aspirin at 100 mg/day.

In the ATLAS ACS 2-TIMI (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction) study[1] of patients with ACS, there was no difference in the risk of stroke between either rivaroxaban 5 mg twice daily or 2.5 mg twice daily, plus low dose aspirin, versus aspirin alone. For any stroke, the combination versus aspirin had an HR of 1.24 (P = 0.25). For only ischemic stroke, the HR was 0.97 (P = 0.89), with no clear stroke protection for either dose of rivaroxaban. Of concern, the intracranial hemorrhage rate was 0.6% for rivaroxaban compared to 0.2% for aspirin alone (P = 0.009).