What is the preferred antiplatelet therapy, ticagrelor (Brillinta) or clopidogrel, for patients after an acute coronary event?

Ticagrelor vs Clopidogrel After Acute Coronary Syndrome

In patients with acute coronary syndrome (ACS), ticagrelor (Brilinta) is preferred over clopidogrel for maintenance P2Y12 inhibitor therapy due to its superior reduction in mortality and cardiovascular events. 1

Comparative Efficacy and Guidelines

• The 2016 ACC/AHA guidelines provide a Class IIa recommendation (Level of Evidence: B-R) for using ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy in patients with ACS treated with DAPT after coronary stent implantation 1

• Ticagrelor demonstrated superior outcomes compared to clopidogrel in the PLATO trial, with significant reductions in:

  • Death from vascular causes (4.0% vs 5.1%, p=0.001) 2
  • Myocardial infarction (5.8% vs 6.9%, p=0.005) 2
  • All-cause mortality (4.5% vs 5.9%, p<0.001) 2

• The European Society of Cardiology recommends ticagrelor (180 mg loading dose, 90 mg twice daily) plus aspirin as first-line DAPT regimen for ACS patients, regardless of initial treatment strategy 3

Pharmacological Advantages of Ticagrelor

• Ticagrelor achieves greater platelet inhibition than clopidogrel, with mean maximum light transmittance aggregometry responses of 28±10% for ticagrelor versus 44±15% for clopidogrel (p<0.001) 4

• Ticagrelor has a more rapid onset of action (30 minutes) compared to clopidogrel (2 hours), providing faster antiplatelet effects in the acute setting 5

• High on-treatment platelet reactivity occurs in only about 3% of patients on ticagrelor compared to 30-40% with clopidogrel, indicating more consistent antiplatelet effects 5, 4

Duration of Therapy

• For patients with ACS treated with DAPT after BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months (Class I, Level of Evidence: B-R) 1

• In patients with high bleeding risk, discontinuation of P2Y12 therapy after 6 months may be reasonable (Class IIb, Level of Evidence: C-LD) 1

• Recent evidence suggests that ticagrelor monotherapy (without aspirin) after 1 month of DAPT may reduce bleeding while maintaining similar MACCE rates compared to continued DAPT 6

Special Considerations

• When using ticagrelor, a daily aspirin dose of 81 mg is recommended (rather than higher doses) 1

• For patients previously on clopidogrel, switching to ticagrelor is recommended early after hospital admission with a 180 mg loading dose, regardless of timing and loading dose of clopidogrel 1, 3

• In patients with prior history of stroke or TIA, prasugrel should not be administered (Class III: Harm, Level of Evidence: B-R), making ticagrelor the preferred potent P2Y12 inhibitor in this population 1

Bleeding Risk Considerations

• While ticagrelor showed no significant difference in overall major bleeding compared to clopidogrel in the PLATO trial (11.6% vs 11.2%, p=0.43), it was associated with higher rates of non-procedure-related bleeding (4.5% vs 3.8%, p=0.03) 2

• To minimize bleeding risk with any DAPT regimen:

  • Use radial over femoral access for coronary procedures 1, 3
  • Prescribe a proton pump inhibitor in combination with DAPT 1, 3
  • Maintain a daily aspirin dose of 75-100 mg 1, 3

When to Consider Clopidogrel Instead

• Clopidogrel remains the P2Y12 inhibitor of choice in patients with:
  • Previous intracranial hemorrhage 1, 3
  • Need for oral anticoagulation 1, 3
  • High bleeding risk with inability to tolerate more potent P2Y12 inhibition 1
  • Intolerance to ticagrelor (e.g., dyspnea, which occurs in some patients) 5

In conclusion, current evidence and guidelines strongly support ticagrelor as the preferred P2Y12 inhibitor over clopidogrel for most patients after ACS due to its superior efficacy in reducing mortality and recurrent cardiovascular events, despite a slightly increased risk of non-procedure-related bleeding.