Should a patient with a cerebrovascular accident (CVA) or stroke be treated with aspirin and apixaban (Eliquis)?

From the Guidelines

The combination of aspirin and Eliquis (apixaban) is generally not recommended for most stroke patients. Typically, a patient would be prescribed either an antiplatelet medication like aspirin OR an anticoagulant like Eliquis, but not both simultaneously. The choice depends on the type of stroke:

• for ischemic strokes caused by atherosclerosis or small vessel disease, aspirin (typically 81-325 mg daily) is often used;
• for cardioembolic strokes, particularly those associated with atrial fibrillation, Eliquis (typically 5 mg twice daily, or 2.5 mg twice daily in certain patients) is preferred. Using both medications together significantly increases bleeding risk without providing substantial additional benefit in most cases, as shown in the 2024 ESC guidelines for the management of atrial fibrillation 1. There are rare exceptions where dual therapy might be considered, such as in patients with both atrial fibrillation and recent coronary stenting, but this requires careful specialist assessment of individual risk factors and should be time-limited. Any stroke patient should also focus on controlling other risk factors like blood pressure, cholesterol, diabetes, and lifestyle modifications including smoking cessation, healthy diet, and regular exercise. The AVERROES trial demonstrated a lower rate of stroke or systemic embolism with apixaban compared with aspirin (HR, 0.45; 95% CI, 0.32–0.62; P < .001), with no significant difference in major bleeding 1. This suggests that apixaban is a preferred option over aspirin for stroke prevention in patients with atrial fibrillation. However, the decision to use either aspirin or apixaban should be based on individual patient risk factors and clinical judgment, taking into account the potential benefits and risks of each treatment option.

From the FDA Drug Label

Apixaban was superior to warfarin for the primary endpoint of reducing the risk of stroke and systemic embolism In AVERROES, patients with nonvalvular atrial fibrillation thought not to be candidates for warfarin therapy were randomized to treatment with apixaban 5 mg orally twice daily (or 2. 5 mg twice daily in selected patients) or aspirin 81 to 324 mg once daily. The primary objective of the study was to determine if apixaban was superior to aspirin for preventing the composite outcome of stroke or systemic embolism AVERROES was stopped early on the basis of a prespecified interim analysis showing a significant reduction in stroke and systemic embolism for apixaban compared to aspirin Table 10: Key Efficacy Outcomes in Patients with Nonvalvular Atrial Fibrillation in AVERROES Apixaban N=2807 n (%/year)Aspirin N=2791 n (%/year) Hazard Ratio (95% CI) P-value Stroke or systemic embolism 51 (1.62) 113 (3.63) 0.45 (0.32,0.62) <0.0001

Patients with stroke should be on apixaban (Eliquis), as it has been shown to be superior to aspirin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation, as demonstrated in the AVERROES study 2.

• Key points:
  • Apixaban reduced the risk of stroke and systemic embolism compared to aspirin
  • Apixaban was superior to warfarin in reducing the risk of stroke and systemic embolism
  • The AVERROES study was stopped early due to the significant reduction in stroke and systemic embolism for apixaban compared to aspirin There is no information that aspirin and Eliquis should be used together for patients with stroke.

From the Research

Stroke Prevention Treatments

• The use of aspirin and Eliquis (apixaban) for stroke prevention in patients with atrial fibrillation has been studied in several clinical trials 3, 4, 5, 6, 7.
• Aspirin has been shown to be effective in reducing the risk of stroke, but the optimal dose is still uncertain 3.
• A study published in 2006 found that a dose of 160 mg/day was effective in preventing recurrent stroke or death in patients with a history of stroke or transient ischemic attack (TIA) 3.
• Another study published in 2013 found that apixaban was more effective than aspirin in reducing the risk of stroke in patients with atrial fibrillation 4.
• A systematic review and meta-analysis published in 2018 found that apixaban was associated with a lower risk of major bleeding compared to warfarin, dabigatran, and rivaroxaban 6.
• A network meta-analysis published in 2016 found that all oral anticoagulants, including apixaban, were more effective than antiplatelet agents in reducing the risk of ischemic stroke and all strokes 7.

Combination Therapy

• The combination of aspirin and dipyridamole has been shown to be superior to aspirin alone for stroke prevention 5.
• The use of combination therapy with aspirin and Eliquis has not been extensively studied, but it may be considered in certain patients with a high risk of stroke 5.
• However, the decision to use combination therapy should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 5.

Safety and Efficacy

• The safety and efficacy of apixaban have been established in several clinical trials, including the ARISTOTLE trial, which found that apixaban was associated with a lower risk of stroke and systemic embolism compared to warfarin 6.
• The risk of major bleeding with apixaban is lower compared to warfarin, dabigatran, and rivaroxaban 6.
• Aspirin is also associated with a risk of bleeding, and the combination of aspirin and Eliquis may increase this risk 3, 5.