What are the implications of using Eliquis (apixaban) and aspirin (acetylsalicylic acid) together?

From the Guidelines

The use of Eliquis (apixaban) and aspirin (acetylsalicylic acid) together is not recommended without an adequate indication, as it may increase the risk of bleeding events without providing a clear benefit in terms of stroke prevention or death 1.

Implications of Combination Therapy

• The combination of antiplatelet agents, such as aspirin, with anticoagulants, like apixaban, should only be used in selected patients with acute vascular disease, such as acute coronary syndromes 1.
• The AVERROES trial demonstrated that apixaban is more effective than aspirin in preventing stroke or systemic embolism in patients with atrial fibrillation, with no significant difference in major bleeding 1.
• However, when apixaban is used in combination with aspirin, the risk of bleeding events increases, and there is no clear benefit in terms of stroke prevention or death 1.

Recommended Dosing

• If aspirin is concomitantly used with apixaban, a dose of 75-100 mg per day is suggested, with concomitant use of a proton pump inhibitor (PPI) to minimize gastrointestinal bleeding 1.

Clinical Considerations

• The decision to use apixaban and aspirin together should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 1.
• The results of ongoing trials, such as the AUGUSTUS trial, may provide further guidance on the use of apixaban and aspirin in patients with atrial fibrillation and acute coronary syndromes 1.

From the FDA Drug Label

Apixaban can cause bleeding which can be serious and rarely may lead to death. This is because apixaban is a blood thinner medicine that reduces blood clotting You may have a higher risk of bleeding if you take apixaban tablets and take other medicines that increase your risk of bleeding, including:

• aspirin or aspirin-containing products
• long-term (chronic) use of nonsteroidal anti-inflammatory drugs (NSAIDs)
• warfarin sodium (COUMADIN®, JANTOVEN®)
• any medicine that contains heparin
• selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
• other medicines to help prevent or treat blood clots

The use of Eliquis (apixaban) and aspirin together may increase the risk of bleeding, as both medications affect blood clotting. Patients taking both medications should be closely monitored for signs and symptoms of bleeding. It is essential to inform your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements, as some may increase the risk of bleeding or stroke when taken with apixaban tablets 2.

From the Research

Implications of Using Eliquis (Apixaban) and Aspirin (Acetylsalicylic Acid) Together

• The use of apixaban and aspirin together has been studied in several clinical trials, including the AUGUSTUS trial 3 and the ARISTOTLE trial 4.
• These trials have shown that apixaban is associated with a lower risk of bleeding and stroke or systemic embolism compared to warfarin, and that aspirin increases the risk of bleeding in patients with atrial fibrillation 3, 4.
• The AUGUSTUS trial found that apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and that aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention 3.
• The ARISTOTLE trial found that apixaban reduced stroke or systemic embolism and caused less major bleeding than warfarin, irrespective of concomitant aspirin use 4.
• A post hoc analysis of the AUGUSTUS trial found that apixaban was associated with lower rates of major or clinically relevant nonmajor bleeding and death or hospitalization than vitamin K antagonists in patients with and without prior stroke, transient ischemic attack, or thromboembolism 5.
• Another analysis of the AUGUSTUS trial found that the use of aspirin immediately and for up to 30 days after an acute coronary syndrome or percutaneous coronary intervention resulted in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events, but that after 30 days, aspirin continued to increase bleeding without significantly reducing ischemic events 6.

Bleeding Risk

• The use of apixaban and aspirin together is associated with an increased risk of bleeding, particularly in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention 3, 4, 5, 6.
• The AUGUSTUS trial found that aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention, particularly in those with an estimated glomerular filtration rate (eGFR) >80 mL·min-1·1.73 m-2 3.
• The ARISTOTLE trial found that apixaban caused less major bleeding than warfarin, irrespective of concomitant aspirin use 4.

Ischemic Events

• The use of apixaban and aspirin together has been shown to reduce the risk of ischemic events, including stroke and systemic embolism, in patients with atrial fibrillation 3, 4, 5, 7.
• The AUGUSTUS trial found that apixaban was associated with lower rates of ischemic events than vitamin K antagonists in patients with and without prior stroke, transient ischemic attack, or thromboembolism 5.
• The ARISTOTLE trial found that apixaban reduced stroke or systemic embolism and caused less major bleeding than warfarin, irrespective of concomitant aspirin use 4.