What is the recommended choice of antiplatelet (single or dual) and anticoagulant therapy for a patient with Acute Coronary Syndrome (ACS) Non-ST-Elevation Myocardial Infarction (NSTEMI), Atrial Fibrillation (AF), and non-obstructive Coronary Artery Disease (CAD)?

Antiplatelet and Anticoagulant Strategy for NSTEMI with AF and Non-Obstructive CAD

In patients with NSTEMI, atrial fibrillation, and non-obstructive CAD, initiate dual therapy with a direct oral anticoagulant (DOAC) plus clopidogrel 75 mg daily for 1 month, then transition to DOAC monotherapy for long-term stroke prevention. 1

Rationale for This Approach

The presence of non-obstructive CAD fundamentally changes the risk-benefit calculation compared to patients requiring PCI with stenting. Without stent thrombosis risk, the primary concern shifts to stroke prevention from AF while minimizing bleeding complications from excessive antithrombotic therapy.

Initial Phase (First Month)

• Start dual therapy immediately: DOAC plus clopidogrel 75 mg daily 1, 2
• Aspirin should be avoided in this specific scenario, as triple therapy (aspirin + clopidogrel + anticoagulant) dramatically increases bleeding risk without proven benefit in non-obstructive CAD 1, 2
• Duration: 1 month only for patients with standard bleeding risk 1, 2

DOAC Selection and Dosing

Choose one of the following based on renal function and bleeding risk:

• Apixaban: 5 mg twice daily (reduce to 2.5 mg twice daily if ≥2 criteria: age ≥80 years, weight ≤60 kg, or creatinine ≥1.5 mg/dL) 1
• Rivaroxaban: 15 mg once daily (reduce to 10 mg once daily if CrCl 30-50 mL/min) 1, 2
• Edoxaban: 60 mg once daily (reduce to 30 mg once daily if CrCl 15-50 mL/min, weight ≤60 kg, or concurrent P-glycoprotein inhibitors) 1
• Dabigatran: 150 mg twice daily (reduce to 110 mg twice daily if high bleeding risk) 1, 2

DOACs are strongly preferred over warfarin in this population 2. If warfarin must be used, target INR 2.0-2.5 (lower end of therapeutic range) with frequent monitoring 3, 1

Long-Term Management (After 1 Month)

• Transition to DOAC monotherapy and discontinue clopidogrel 1, 2
• Continue DOAC indefinitely based on CHA₂DS₂-VASc score for stroke prevention 1, 4
• Do not continue antiplatelet therapy beyond 1 month in the absence of obstructive CAD requiring revascularization 1, 2

Risk Assessment Framework

Bleeding Risk Stratification (HAS-BLED Score)

Calculate before initiating therapy 1, 2:

• HAS-BLED ≥3 = High bleeding risk: Use 1 month dual therapy only, then DOAC monotherapy 1
• HAS-BLED 0-2 = Standard risk: Can consider 1-3 months dual therapy if additional ischemic risk factors present 2

Stroke Risk Assessment (CHA₂DS₂-VASc)

This determines the need for long-term anticoagulation 1, 4:

• Score ≥2 in men or ≥3 in women: Strong indication for indefinite anticoagulation
• The NSTEMI event itself does not change this calculation

Critical Distinctions from Obstructive CAD with Stenting

This recommendation differs fundamentally from patients requiring PCI with stenting, where:

• Standard NSTEMI guidelines recommend DAPT (aspirin + P2Y12 inhibitor) for 12 months 3, 5
• Patients with stents and AF require initial triple therapy (aspirin + clopidogrel + anticoagulant) for 1-3 months 3, 1, 2

In non-obstructive CAD, there is no stent thrombosis risk, eliminating the rationale for prolonged dual antiplatelet therapy or triple therapy. 1, 2

Bleeding Risk Reduction Measures

Implement these universally 1, 2:

• Proton pump inhibitor: Mandatory for all patients on combined antithrombotic therapy 1, 2
• Avoid NSAIDs completely 1, 2
• Monitor renal function every 3-6 months and adjust DOAC dosing accordingly 1
• Reassess HAS-BLED score at each follow-up visit 4

Common Pitfalls to Avoid

Pitfall 1: Continuing Triple Therapy Beyond 1 Month

Many clinicians reflexively continue aspirin indefinitely after any ACS event. In non-obstructive CAD with AF, prolonged triple therapy increases major bleeding by 2-3 fold without reducing ischemic events. 1, 2, 6

Pitfall 2: Using Standard NSTEMI DAPT Duration

The 12-month DAPT recommendation from ACS guidelines 3, 5 applies to patients with obstructive CAD undergoing revascularization. Non-obstructive CAD patients derive no benefit from prolonged antiplatelet therapy and face only bleeding risk. 1, 2

Pitfall 3: Choosing Ticagrelor or Prasugrel Over Clopidogrel

While ticagrelor and prasugrel are preferred P2Y12 inhibitors in standard NSTEMI 3, clopidogrel is specifically recommended when combined with anticoagulation due to lower bleeding risk 3, 1, 2

Pitfall 4: Discontinuing Anticoagulation After 12 Months

The AF-related stroke risk persists indefinitely. DOAC monotherapy must continue lifelong based on CHA₂DS₂-VASc score, not the temporal relationship to the NSTEMI event. 1, 4

Special Considerations

If Diagnostic Angiography is Planned

• Continue dual therapy (DOAC + clopidogrel) through the procedure 1
• Hold morning DOAC dose on procedure day if using twice-daily agent 1
• Resume full regimen 6-8 hours post-procedure if hemostasis achieved 1

If Patient Has High Ischemic Risk Despite Non-Obstructive CAD

Examples: Extensive plaque burden, diabetes, prior MI, multivessel disease on angiography

• Maximum duration: 3 months dual therapy, then DOAC monotherapy 2
• Do not extend beyond 3 months even with multiple risk factors, as bleeding risk outweighs benefit 1, 2

If Patient Develops Bleeding on Dual Therapy

• Immediately discontinue clopidogrel and continue DOAC monotherapy 1
• Reassess bleeding source and optimize PPI therapy 1, 2
• Consider dose reduction of DOAC if appropriate criteria met 1