Should Aspirin (ASA) be continued in a patient on Apixaban (Eliquis)?

From the Guidelines

No, aspirin (ASA) should generally be discontinued when a patient is on apixaban, as continuing both medications together significantly increases bleeding risk without providing additional benefit for most patients. Apixaban alone is sufficient for anticoagulation in conditions like atrial fibrillation or venous thromboembolism. The only exception would be in specific cases of recent acute coronary syndrome or coronary stent placement, where dual therapy might be temporarily indicated under careful specialist supervision, as suggested by the 2020 ACC expert consensus decision pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease 1.

If the patient has both a cardiovascular indication for aspirin and a separate indication for anticoagulation, the risks and benefits should be carefully weighed by their healthcare provider, considering factors such as the patient's history of acute coronary syndrome (ACS), the type and location of coronary stents, and other clinical factors that may influence the decision to continue or discontinue aspirin therapy 1. Patients should not discontinue either medication without consulting their physician first. If the patient experiences any unusual bleeding while on apixaban, they should seek immediate medical attention. The mechanism behind the increased bleeding risk is that both medications affect hemostasis through different pathways - apixaban inhibits factor Xa in the coagulation cascade while aspirin inhibits platelet aggregation.

Some key considerations in managing patients on apixaban and aspirin include:

• The duration of dual antiplatelet therapy (DAPT) and the safety of shortening it, which may be influenced by the characteristics and morphology of the vessel, lesion, and stent location 1.
• The use of proton pump inhibitors (PPIs) or histamine H2-receptor antagonists to reduce the risk of gastrointestinal bleeding in patients on multiple antithrombotic agents 1.
• The importance of careful attention to time spent in the therapeutic range for patients on vitamin K antagonists (VKAs) to reduce bleeding risk 1.
• The consideration of cost and patient preference when making decisions regarding choice of therapy 1.

Overall, the decision to continue or discontinue aspirin in patients on apixaban should be individualized and based on a careful assessment of the patient's risk factors and clinical circumstances, with a focus on minimizing the risk of bleeding and maximizing the benefits of anticoagulation therapy.

From the FDA Drug Label

Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs)

The use of ASA with apixaban increases the risk of bleeding. There is no direct information in the label that suggests ASA should be continued or discontinued when taking apixaban. However, due to the increased risk of bleeding, it is recommended to use caution when concomitantly using ASA and apixaban. The decision to continue ASA should be made on a case-by-case basis, considering the individual patient's risk of bleeding and thrombotic events 2.

From the Research

ASA and Apixaban Combination

• The combination of ASA and apixaban has been studied in various contexts, including cancer-associated venous thromboembolism and peripheral artery disease 3, 4, 5.
• In patients with cancer-associated venous thromboembolism, the concomitant administration of anticancer agents and apixaban did not affect the risk of recurrent VTE or major bleeding 3.
• In patients with peripheral artery disease, the combination of rivaroxaban (a novel oral anticoagulant) and ASA has been shown to reduce the risk of cardiovascular events, but may increase the risk of bleeding 4, 5.
• The use of apixaban with ASA has not been directly studied in the context of peripheral artery disease, but the available evidence suggests that the combination of a novel oral anticoagulant and ASA may be beneficial in reducing cardiovascular events 5.

Safety and Efficacy

• The safety and efficacy of apixaban with ASA have been evaluated in various studies, including those on cancer-associated venous thromboembolism and peripheral artery disease 3, 4, 5.
• In general, the combination of apixaban and ASA has been shown to be effective in reducing the risk of recurrent VTE and cardiovascular events, but may increase the risk of bleeding 3, 4, 5.
• The use of apixaban with ASA requires careful consideration of the potential benefits and risks, including the risk of bleeding and the need for dose adjustment 6.

Dose Adjustment

• The need for dose adjustment when using apixaban with ASA has been evaluated in several studies, including those on the pharmacokinetics of apixaban and the effects of concomitant medications on apixaban concentrations 6.
• The available evidence suggests that the concomitant use of strong P-glycoprotein inhibitors and CYP3A4 inhibitors may increase apixaban concentrations and require dose adjustment 6.
• The use of apixaban with ASA requires careful consideration of the potential need for dose adjustment and the monitoring of apixaban concentrations to minimize the risk of bleeding and other adverse events 6.