What are the indications for apixaban (Apixaban) 5mg twice daily (bid) and clopidogrel (Clopidogrel) in patients with non-valvular atrial fibrillation and coronary artery disease?

Indications for Apixaban 5mg BID and Clopidogrel

In patients with non-valvular atrial fibrillation and coronary artery disease requiring PCI or with acute coronary syndrome, the recommended regimen is dual antithrombotic therapy (DAT) consisting of apixaban 5 mg twice daily plus clopidogrel, which is the default strategy after a brief periprocedural period. 1

Specific Clinical Scenarios

After PCI or ACS in AF Patients

• Periprocedural period (up to 1 week): Triple therapy (apixaban 5 mg BID + aspirin + clopidogrel) may be used immediately post-procedure, with aspirin discontinued within 1 week in most patients 1

• 1 week to 12 months post-PCI: Dual therapy with apixaban 5 mg BID plus clopidogrel is the recommended default strategy 1

• Beyond 12 months: Apixaban monotherapy (5 mg BID) is recommended, with discontinuation of all antiplatelet therapy 1

High Ischemic Risk Exceptions

• Triple therapy extension: In selected patients with high ischemic risk (complex PCI, left main stenting, multivessel disease), triple therapy may be considered for up to 1 month, and in exceptional cases up to 6 months 1

• Aspirin should NOT exceed 100 mg daily when used in combination with apixaban 1

Apixaban Dosing Criteria

Standard dose (5 mg BID) is used for most patients 2

Reduced dose (2.5 mg BID) is indicated ONLY when at least 2 of the following 3 criteria are present: 3, 2

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

Evidence Supporting This Regimen

AUGUSTUS Trial Findings

• Apixaban-based dual therapy reduced major or clinically relevant non-major bleeding by 31% compared to warfarin-based triple therapy (HR 0.69,95% CI 0.58-0.81) 1

• Death plus hospitalization was lower with apixaban (HR 0.83,95% CI 0.74-0.93) 1

• No difference in ischemic outcomes between apixaban and warfarin (HR 0.93,95% CI 0.75-1.16), confirming non-inferiority 1

Why Clopidogrel Over Other P2Y12 Inhibitors

• Clopidogrel is strongly preferred over prasugrel or ticagrelor when combined with oral anticoagulation due to lower bleeding risk 1

• Ticagrelor and prasugrel as part of triple therapy are NOT recommended 1

• Over 90% of patients in major trials (AUGUSTUS, RE-DUAL PCI, PIONEER AF-PCI) used clopidogrel as the P2Y12 inhibitor 1

Critical Pitfalls to Avoid

Common Errors

• Do NOT use aspirin monotherapy or aspirin plus clopidogrel without anticoagulation in AF patients, as this provides inadequate stroke protection (only 19% stroke reduction with aspirin alone) 4

• Do NOT continue triple therapy beyond 1 week in most patients, as bleeding risk outweighs ischemic benefit 1

• Do NOT use reduced-dose apixaban (2.5 mg BID) unless 2 of 3 dose-reduction criteria are met, as underdosing increases stroke risk 3

• Do NOT double the apixaban dose if missed; take the next scheduled dose 2

Contraindications

• Apixaban must be discontinued 48 hours before elective surgery with moderate-to-high bleeding risk, or 24 hours before low-risk procedures 2

• Patients with mechanical heart valves or moderate-to-severe mitral stenosis should NOT receive apixaban 2

Medically Managed ACS (No PCI)

• In AF patients with ACS managed medically (no stent), apixaban 5 mg BID plus clopidogrel for at least 6 months should be considered 1

• This avoids the bleeding risk of triple therapy while maintaining adequate protection against both coronary and embolic events 1

Monitoring Requirements

• Renal function should be reassessed at least annually, as creatinine clearance affects apixaban dosing decisions 3

• Regular assessment of bleeding risk using HAS-BLED score (≥3 indicates high bleeding risk) guides duration of combination therapy 1