What are the indications for low‑dose aspirin (81 mg) and apixaban 5 mg twice daily, and when should the apixaban dose be reduced or an alternative used because of bleeding risk?

Indications for Aspirin 81 mg and Apixaban 5 mg BID

Aspirin 81 mg Daily Indications

Low-dose aspirin (81 mg daily) is indicated for secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD), including those with prior myocardial infarction, stroke, stable angina, or peripheral artery disease. 1, 2

Primary Prevention (Limited Role)

• For primary prevention, aspirin 81 mg may be considered (Class IIb) in adults aged 40-59 years with ≥10% 10-year ASCVD risk, but only after individualized discussion weighing bleeding risk against modest benefit. 1, 3
• The USPSTF recommends against initiating aspirin for primary prevention in adults ≥60 years due to lack of net benefit and increased bleeding risk. 3
• Aspirin may be reasonable in select primary prevention patients with coronary artery calcium (CAC) score ≥100 who lack bleeding contraindications. 1

Secondary Prevention Settings

• Continue aspirin indefinitely in patients with established coronary artery disease, prior MI, ischemic stroke/TIA, or peripheral arterial disease. 2
• For patients <1 year post-CABG surgery, continue aspirin; beyond 1 year post-CABG, aspirin can be stopped if anticoagulation is established. 1
• In myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia), aspirin 81-100 mg daily reduces thrombotic complications, though use cautiously if acquired von Willebrand disease is present. 1

Critical Contraindications

• Absolute contraindications include: known aspirin allergy, active pathological bleeding, history of NSAID-associated upper GI bleeding, active peptic ulcer disease, and concurrent anticoagulation without gastroprotection. 4, 5

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Apixaban 5 mg BID Indications

Apixaban 5 mg twice daily is indicated for stroke prevention in nonvalvular atrial fibrillation and for treatment/prevention of venous thromboembolism (VTE). 1

Atrial Fibrillation

• Apixaban is superior to aspirin for stroke prevention in AF patients, with similar major bleeding rates. The AVERROES trial demonstrated clear superiority of apixaban 5 mg BID over aspirin (81-325 mg daily) in patients unsuitable for warfarin. 1
• Apixaban is preferred over warfarin due to lower bleeding risk and no need for INR monitoring. 1

Venous Thromboembolism

• For acute VTE treatment, apixaban requires a 7-day initiation dose of 10 mg BID, then 5 mg BID for continued treatment. 1
• For cancer-associated VTE, DOACs (including apixaban) are preferred over LMWH and warfarin, though caution is needed in GI/genitourinary malignancies due to higher bleeding risk. 1
• After 6 months of full-dose anticoagulation, apixaban can be reduced to 2.5 mg BID for extended VTE prevention in select patients. 1

Dose Reduction Criteria for Apixaban

Reduce apixaban to 2.5 mg BID when ≥2 of the following are present: 1

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

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Combining Aspirin and Apixaban: High Bleeding Risk

The combination of aspirin 81 mg with apixaban 5 mg BID significantly increases major bleeding risk and should be avoided unless there is a compelling indication requiring dual antithrombotic therapy. 1, 6

When Combination May Be Necessary

• Post-PCI in AF patients: Triple therapy (apixaban + aspirin + P2Y12 inhibitor) may be used for up to 30 days in high thrombotic risk/low bleeding risk patients, then transition to dual therapy (apixaban + P2Y12 inhibitor, preferably clopidogrel) for up to 12 months. 1
• After 12 months post-PCI, continue apixaban monotherapy and discontinue all antiplatelet agents. 1

Bleeding Risk Considerations

• Major bleeding with apixaban vs aspirin occurs at 1.71 vs 0.94 per 100 patient-years (HR 1.80). 6
• Gastrointestinal bleeding is particularly elevated with apixaban (HR 2.23), though intracranial and fatal bleeding rates are similar. 6
• Risk factors for major bleeding include: NSAID use (HR 10.25), cancer (HR 2.87), apixaban use (HR 1.84), and increasing age (HR 1.47 per 5 years). 6

Gastroprotection Mandate

• When combining aspirin with apixaban (or any anticoagulant), add a proton pump inhibitor for GI protection. 4, 7
• This is especially critical in patients with prior GI bleeding, age >60 years, or concurrent NSAID use. 4

Monitoring Requirements

If combination therapy proceeds, monitor: 4

• Blood pressure, BUN/creatinine, liver function tests, CBC, and fecal occult blood at baseline and periodically
• Discontinue if BUN/creatinine doubles, hypertension worsens, or liver enzymes exceed 3× upper limit of normal

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Practical Algorithm for Decision-Making

For patients requiring anticoagulation (AF or VTE):

1. Use apixaban 5 mg BID (or 2.5 mg BID if dose reduction criteria met) as monotherapy. 1
2. Avoid adding aspirin unless acute coronary syndrome or recent PCI (<12 months). 1
3. If post-PCI, limit triple therapy to ≤30 days, then dual therapy (apixaban + clopidogrel) for ≤12 months. 1
4. Always add PPI when combining antiplatelet and anticoagulant therapy. 4, 7

For patients requiring aspirin (secondary ASCVD prevention):

1. Use aspirin 81 mg daily as monotherapy. 1, 2
2. If AF develops, transition to apixaban monotherapy and discontinue aspirin (unless recent ACS/PCI). 1
3. Never combine aspirin with NSAIDs; if pain control needed, use acetaminophen or consider short-term opioids. 4