A patient with a drug‑eluting stent placed in the left anterior descending artery four weeks ago is on aspirin 81 mg daily and clopidogrel 75 mg daily and now has dyspnea, hot flashes, and burning leg sensations suggestive of clopidogrel intolerance; how should his antiplatelet therapy be managed?

Management of Clopidogrel Intolerance After Recent DES Placement

Switch from clopidogrel to aspirin monotherapy (81 mg daily) immediately, as this patient is only 4 weeks post-DES and cannot safely discontinue all P2Y12 inhibitor therapy, but clopidogrel must be stopped due to intolerance. 1

Immediate Action

Discontinue clopidogrel immediately given the clear symptoms of intolerance (dyspnea, hot flashes, burning leg sensations). 2

Continue aspirin 81 mg daily indefinitely as the cornerstone of antiplatelet therapy in all patients with coronary artery disease. 1

Critical Timing Consideration

This patient is at extremely high risk for stent thrombosis at only 4 weeks post-DES placement. The first 6 months after DES implantation represent the highest-risk period, and early discontinuation of P2Y12 inhibitor therapy within the first 6 months is a major predictor of stent thrombosis (hazard ratio 13.74). 3

Alternative P2Y12 Inhibitor Options

Since dual antiplatelet therapy (DAPT) is mandatory for at least 12 months after DES placement 1, you must substitute another P2Y12 inhibitor:

Option 1: Ticagrelor (Preferred)

• Loading dose: 180 mg once, then 90 mg twice daily 1, 4
• Advantages: No cross-reactivity with clopidogrel (different chemical structure—not a thienopyridine), more consistent platelet inhibition, does not require hepatic conversion 4
• Disadvantages: Twice-daily dosing may affect compliance, higher cost 4
• Contraindications: Prior intracranial hemorrhage, history of stroke/TIA (use with caution) 4

Option 2: Prasugrel

• Loading dose: 60 mg once, then 10 mg daily 1
• Advantages: More potent than clopidogrel, once-daily dosing 1
• Absolute contraindication: Prior stroke or TIA 1
• Caution: Higher bleeding risk than clopidogrel 3

Cross-Reactivity Warning

Cross-reactivity among thienopyridines has been reported. 1 Since both clopidogrel and prasugrel are thienopyridines, there is potential for cross-reactivity. Ticagrelor is NOT a thienopyridine and therefore has no cross-reactivity risk. 4

Recommended Algorithm

1. Immediately discontinue clopidogrel 2

2. Continue aspirin 81 mg daily 1

3. Initiate ticagrelor:

   • Loading dose: 180 mg immediately 4
   • Maintenance: 90 mg twice daily 1, 4
   • Duration: Complete 12 months of DAPT from stent placement 1

4. If ticagrelor is contraindicated or not tolerated:

   • Consider prasugrel ONLY if patient has no history of stroke/TIA 1
   • Loading dose: 60 mg, then 10 mg daily 1

5. If both ticagrelor and prasugrel are contraindicated:

   • Continue aspirin monotherapy and accept increased stent thrombosis risk 1
   • Consider early cardiology consultation for risk stratification

Duration of Therapy

DAPT must continue for at least 12 months after DES placement in this patient who received the stent 4 weeks ago. 1 After 12 months, aspirin should be continued indefinitely. 1

Common Pitfall to Avoid

Do NOT simply discontinue clopidogrel and continue aspirin monotherapy at 4 weeks post-DES. This dramatically increases stent thrombosis risk, which is often catastrophic (myocardial infarction or death). 5, 3 The patient requires substitution with an alternative P2Y12 inhibitor, not discontinuation of dual antiplatelet therapy. 1