In a patient with atrial fibrillation taking apixaban (Eliquis) for stroke prevention, can aspirin (acetylsalicylic acid) be added safely?

Adding Aspirin to Apixaban in Atrial Fibrillation: Not Recommended

Do not add aspirin to apixaban in patients with atrial fibrillation taking anticoagulation for stroke prevention. The combination increases bleeding risk without providing additional protection against stroke or death. 1

Why This Combination Should Be Avoided

No Benefit, Only Harm

• The 2024 European Society of Cardiology guidelines explicitly state that combining antiplatelet drugs with anticoagulants should only occur in selected patients with acute vascular disease (e.g., acute coronary syndromes), not for routine stroke prevention in atrial fibrillation. 1

• Adding antiplatelet treatment to anticoagulation is not recommended in patients with AF to prevent recurrent embolic stroke (Class III recommendation, Level B evidence). 1

• Bleeding events are more common when antithrombotic agents are combined, and no clear benefit has been observed in terms of prevention of stroke or death. 1

Evidence from Clinical Trials

• In the ARISTOTLE trial, patients taking apixaban with concomitant aspirin had major bleeding rates of 3.10% per year compared to 1.82% per year in those without aspirin. The relative benefit of apixaban over warfarin was maintained regardless of aspirin use, but absolute bleeding rates were substantially higher with aspirin. 2

• The AVERROES trial demonstrated that apixaban was superior to aspirin alone for stroke prevention (hazard ratio 0.45), but this does not justify combining them—it shows apixaban should replace aspirin, not be added to it. 1

FDA Drug Label Warning

• The apixaban FDA label explicitly warns that patients have a higher risk of bleeding if they take apixaban and other medicines that increase bleeding risk, including aspirin or aspirin-containing products. 3

• The label specifically instructs patients to tell their doctor if they take aspirin, as it is listed among medications that increase bleeding risk when combined with apixaban. 3

When Aspirin Might Be Considered (Rare Exceptions)

Acute Coronary Syndrome or Recent Stenting

• The only scenario where combining aspirin with apixaban is appropriate is in patients with acute coronary syndromes or recent coronary stent placement (within the past 12 months). 1

• For AF patients undergoing PCI/stenting with low bleeding risk (HAS-BLED 0-2), triple therapy (apixaban + aspirin + P2Y12 inhibitor) may be used for 1 month, followed by dual therapy (apixaban + single antiplatelet) for up to 12 months, then apixaban alone. 1

• After 12 months from an acute coronary event, aspirin should be discontinued and the patient maintained on apixaban monotherapy. 1

Stable Coronary Artery Disease

• In AF patients with stable coronary artery disease (>12 months from acute event), adding aspirin to anticoagulation provides no reduction in MI or coronary death but increases bleeding risk by more than 50%. 1

• A large Danish cohort study showed that adding aspirin to vitamin K antagonists in stable coronary disease increased bleeding (HR 1.50) without reducing MI or coronary death (HR 1.12). 1

Common Clinical Pitfalls

"Low-Dose" Aspirin Is Not Safe

• Even low-dose aspirin (81 mg daily) significantly raises bleeding risk without proven benefit for stroke prevention in atrial fibrillation. 4

• The 2012 ESC guidelines note that the risk of major bleeding with aspirin monotherapy should be considered as being similar to oral anticoagulation, especially in elderly patients. 1

Antiplatelet Drugs Are Not Alternatives to Anticoagulation

• Antiplatelet drugs such as aspirin and clopidogrel are not an alternative to oral anticoagulation and should not be used for stroke prevention in AF, as they can lead to potential harm, especially among elderly patients. 1

• The ACTIVE W trial was stopped prematurely because warfarin was clearly superior to the combination of aspirin plus clopidogrel for stroke prevention in AF. 1

Inappropriate Continuation of Aspirin

• The combination of oral anticoagulation with antiplatelet agents (especially aspirin) without an adequate indication occurs frequently in clinical practice. 1

• Unless the patient has had a myocardial infarction, stroke, or coronary stent placement within the past 12 months, aspirin should be discontinued immediately. 4

What to Do Instead

Use Apixaban Alone

• For stroke prevention in atrial fibrillation, apixaban monotherapy at the appropriate dose (5 mg twice daily, or 2.5 mg twice daily if dose-reduction criteria are met) is the recommended approach. 5

• Dose reduction to 2.5 mg twice daily is indicated when any two of the following are present: age ≥80 years, serum creatinine ≥1.5 mg/dL, or body weight ≤60 kg. 5

For Pain Management

• If analgesia is needed, acetaminophen (up to 3-4 g daily) is recommended because it does not increase bleeding risk. 4

• NSAIDs (ibuprofen, naproxen) should be avoided as they also increase bleeding risk when combined with anticoagulation. 4, 3

Monitor Bleeding Risk

• Assess bleeding risk using the HAS-BLED score at every patient contact, with scores ≥3 indicating high risk requiring more frequent review. 1

• Address modifiable bleeding risk factors including uncontrolled blood pressure, concomitant drugs (aspirin, NSAIDs), and alcohol use. 1

• Check renal function at least annually, as impaired kidney function prolongs apixaban exposure and heightens bleeding risk. 5