Which dual antiplatelet therapy (DAPT) agent to start first, aspirin or a P2Y12 inhibitor (e.g. clopidogrel), after bleeding has improved?

Restarting Dual Antiplatelet Therapy After Bleeding: Start with Aspirin First

After bleeding has improved, aspirin should be restarted first, followed by the P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) when adequate hemostasis is achieved. 1

Rationale for Restarting Aspirin First

The approach to restarting dual antiplatelet therapy (DAPT) after bleeding should follow a sequential pattern based on established guidelines:

1. Initial Management:

   • For patients with coronary stents on DAPT, withholding both antiplatelet agents simultaneously is not recommended due to high risk of stent thrombosis 1
   • The European Society of Cardiology (ESC) and Asian Pacific Association of Gastroenterology (APAGE) guidelines recommend continuing aspirin and withholding the P2Y12 inhibitor during active bleeding 1

2. Resumption Strategy:

   • Aspirin should be restarted as soon as hemostasis is achieved 1
   • P2Y12 inhibitors should be resumed after adequate hemostasis, preferably within 5 days after endoscopic hemostasis for patients with drug-eluting coronary stents 1

Practical Algorithm for DAPT Resumption After Bleeding

1. During Active Bleeding:

   • Continue low-dose aspirin (75-100 mg daily) if possible
   • Temporarily withhold P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel)
   • Use proton pump inhibitor infusion for gastrointestinal bleeding 1

2. After Hemostasis is Achieved:

   • Step 1: Resume/continue aspirin immediately
   • Step 2: Resume P2Y12 inhibitor within 5 days (preferably sooner if bleeding risk allows)
   • Step 3: Consider loading dose of P2Y12 inhibitor when restarting to achieve rapid platelet inhibition 1

3. P2Y12 Inhibitor Selection After Bleeding:

   • For patients with high bleeding risk: Consider clopidogrel (less potent, lower bleeding risk)
   • For patients with acute coronary syndrome and acceptable bleeding risk: Consider ticagrelor (preferred) or prasugrel 1, 2

Special Considerations

• Stent Thrombosis Risk: The risk of stent thrombosis is highest within the first month after placement, making prompt resumption of DAPT crucial 1

• Bleeding Risk Assessment: Use validated risk scores (e.g., PRECISE-DAPT) to guide duration of therapy after resumption 1

• Proton Pump Inhibitors: Always add a PPI when resuming DAPT to reduce risk of recurrent gastrointestinal bleeding 1, 2

• Dosing Considerations: Use low-dose aspirin (75-100 mg daily) to minimize bleeding risk while maintaining efficacy 1, 2

Important Caveats

• If bleeding risk remains prohibitively high, consider maintaining only aspirin therapy and consulting with cardiology for individualized recommendations

• For patients with very recent stent placement (<1 month), the thrombotic risk is extremely high, and every effort should be made to maintain at least aspirin therapy continuously

• For patients with drug-eluting stents, early resumption of the P2Y12 inhibitor (within 5 days) is particularly important to prevent stent thrombosis 1

• If the patient is on ticagrelor and experienced significant bleeding, consider switching to clopidogrel when restarting P2Y12 inhibitor therapy to reduce bleeding risk 2

By following this sequential approach of restarting aspirin first followed by the P2Y12 inhibitor, you can balance the competing risks of recurrent bleeding and thrombotic events in patients requiring dual antiplatelet therapy.