When is ticagrelor (P2Y12 inhibitor) preferred over other antiplatelet agents in patients with acute coronary syndromes (ACS)?

When to Prefer Ticagrelor in Acute Coronary Syndromes

Ticagrelor is preferred over other antiplatelet agents in patients with acute coronary syndromes (ACS) who are not at high bleeding risk and do not have a history of intracranial hemorrhage. According to the most recent guidelines, ticagrelor offers superior reduction in ischemic events compared to clopidogrel while maintaining a manageable bleeding risk profile 1.

Primary Indications for Ticagrelor

• ACS patients undergoing PCI: Ticagrelor is recommended in preference to clopidogrel for patients with ACS (both NSTE-ACS and STEMI) undergoing percutaneous coronary intervention 1

• Medically managed ACS: Ticagrelor is recommended over clopidogrel for patients with ACS who are managed with medical therapy alone (without revascularization) 1

• Post-PCI monotherapy: In patients who have tolerated dual antiplatelet therapy with ticagrelor, transition to ticagrelor monotherapy is recommended 1 month after PCI 1, 2

Specific Clinical Scenarios Where Ticagrelor is Preferred

1. ACS patients treated with an early invasive or ischemia-guided strategy 1

   • Provides greater platelet inhibition than clopidogrel
   • Demonstrated reduction in cardiovascular death, MI, and stroke

2. Patients with high ischemic risk 1

   • Particularly beneficial in patients with elevated troponin
   • Patients with diabetes mellitus
   • Complex PCI procedures (multiple stents, bifurcation lesions)

3. Switching from clopidogrel to ticagrelor 1

   • In patients with ACS previously exposed to clopidogrel, switching to ticagrelor is recommended early after hospital admission
   • Loading dose of 180 mg irrespective of timing and loading dose of clopidogrel

Contraindications and Cautions for Ticagrelor

• Absolute contraindications:

  • Previous intracranial hemorrhage 1
  • Active bleeding 1

• Relative contraindications/caution needed:

  • High bleeding risk (PRECISE-DAPT score ≥25) 1
  • Patients requiring long-term oral anticoagulation (clopidogrel preferred) 1
  • Patients with severe respiratory conditions (due to risk of dyspnea) 3

Ticagrelor vs. Prasugrel

Both ticagrelor and prasugrel are preferred over clopidogrel in ACS patients undergoing PCI 1. However:

• Choose ticagrelor over prasugrel when:

  • Patient has history of stroke or TIA (prasugrel is contraindicated) 1
  • Medical management without PCI is planned (prasugrel not recommended) 1
  • Patient requires upstream therapy before coronary anatomy is known 1
  • Patient is ≥75 years of age or <60 kg (prasugrel requires dose reduction) 1

• Consider prasugrel over ticagrelor when:

  • Patient has history of dyspnea or asthma (ticagrelor can cause dyspnea) 3
  • Compliance with twice-daily dosing might be an issue (prasugrel is once daily) 4

Dosing and Duration

• Loading dose: 180 mg 4
• Maintenance dose: 90 mg twice daily 4
• Duration:
  • Standard recommendation: 12 months after ACS 1
  • Consider shorter duration (6 months) if high bleeding risk 1
  • Consider ticagrelor monotherapy after 1 month of DAPT 1, 5, 2

Practical Considerations

• Perioperative management: Discontinue ticagrelor 3-5 days before elective surgery; for urgent CABG, interruption for at least 24 hours is recommended 1

• Monitoring: Routine platelet function testing is not recommended to adjust therapy 1, 4

• Bleeding management: Consider proton pump inhibitor in patients at risk of gastrointestinal bleeding 1, 4

• Cost and access: Consider availability and cost, as these may impact adherence

Summary Algorithm for P2Y12 Inhibitor Selection in ACS

1. First-line therapy for most ACS patients: Ticagrelor
2. Consider prasugrel instead if: No history of stroke/TIA, coronary anatomy known, PCI planned, and no issues with age/weight restrictions
3. Use clopidogrel when: Ticagrelor and prasugrel are contraindicated, unavailable, or not tolerated, or when patient requires oral anticoagulation

By following this evidence-based approach to antiplatelet selection, clinicians can optimize outcomes by reducing ischemic events while managing bleeding risk in patients with ACS.