Can aspirin be given to a patient with Non-ST-Elevation Myocardial Infarction (NSTEMI) on Eliquis (apixaban)?

From the Guidelines

Aspirin can be given to a patient with Non-ST-Elevation Myocardial Infarction (NSTEMI) on Eliquis (apixaban), but this requires careful consideration of bleeding risk. The standard recommendation is to administer a loading dose of 162-325 mg of non-enteric coated aspirin, followed by a maintenance dose of 81 mg daily, as stated in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. This dual antithrombotic therapy is important because aspirin and apixaban work through different mechanisms - aspirin inhibits platelet aggregation while apixaban is a direct factor Xa inhibitor that prevents clot formation. For patients with NSTEMI, this combination helps reduce the risk of recurrent cardiac events. However, the combination does increase bleeding risk, so patients should be monitored closely for any signs of bleeding, including bruising, blood in stool or urine, or unusual bleeding from gums. Regular complete blood count monitoring is advisable, as recommended in the guideline 1. In some high-bleeding-risk patients, a lower aspirin maintenance dose (81 mg) is preferred, and the duration of dual therapy might be shortened based on individual risk assessment, as suggested in the guideline 1. Patients should also be educated about bleeding precautions and when to seek medical attention. Key points to consider include:

• Aspirin should be continued indefinitely in patients with NSTEMI who tolerate it, as stated in the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction 1.
• The maintenance dose of aspirin should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all other patients, as recommended in the 2014 AHA/ACC guideline 1.
• Patients should be monitored closely for signs of bleeding and educated about bleeding precautions, as emphasized in the guideline 1.

From the FDA Drug Label

7.3 Anticoagulants and Antiplatelet Agents Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk, post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

Aspirin can be given to a patient with Non-ST-Elevation Myocardial Infarction (NSTEMI) on Eliquis (apixaban), but it increases the risk of bleeding.

• The rate of ISTH major bleeding was 2.8% per year with apixaban versus 0.6% per year with placebo in patients receiving single antiplatelet therapy.
• In ARISTOTLE, concomitant use of aspirin increased the bleeding risk on apixaban from 1.8% per year to 3.4% per year 2.

From the Research

Aspirin and Eliquis (Apixaban) in NSTEMI

• The use of aspirin in patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) on Eliquis (apixaban) is a complex issue, with several studies providing insights into the safety and efficacy of this combination 3, 4, 5, 6.
• According to a 2014 study, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the gold standard for patients with acute coronary syndrome, including NSTEMI 3.
• A 2024 narrative review suggests that patients with NSTEMI should be initiated on anticoagulation, such as heparin or low molecular weight heparin, during the acute phase, and that longer-term management may involve triple antithrombotic therapy with a direct oral anticoagulant (DOAC), aspirin, and clopidogrel 4.
• The APPRAISE trial, published in 2009, investigated the use of apixaban in combination with antiplatelet therapy after acute coronary syndrome, and found that apixaban increased the risk of bleeding, but also reduced the risk of ischemic events 5.
• A post hoc analysis of the APPRAISE-2 trial, published in 2019, found that bleeding risk was increased in patients receiving triple therapy with apixaban, thienopyridine, and aspirin, compared to those receiving dual therapy with apixaban and aspirin 6.

Bleeding Risk and Ischemic Events

• The studies suggest that the use of aspirin in patients with NSTEMI on Eliquis (apixaban) may increase the risk of bleeding, particularly when used in combination with other antiplatelet agents 5, 6.
• However, the same studies also suggest that this combination may reduce the risk of ischemic events, such as myocardial infarction and stroke 4, 5.
• The balance between the risk of bleeding and the benefit of reducing ischemic events must be carefully considered in each individual patient, taking into account their unique clinical characteristics and risk factors 7.

Clinical Implications

• The use of aspirin in patients with NSTEMI on Eliquis (apixaban) should be guided by current clinical guidelines and the results of ongoing research 3, 4.
• Clinicians should carefully weigh the potential benefits and risks of this combination, and consider alternative antithrombotic strategies in patients at high risk of bleeding or ischemic events 5, 6.