What is Brillinta (ticagrelor)?

Brilinta (Ticagrelor): A Potent Antiplatelet Medication

Brilinta (ticagrelor) is an oral, direct-acting P2Y12 receptor antagonist that provides more rapid, potent, and consistent platelet inhibition compared to clopidogrel, significantly reducing mortality and cardiovascular events in patients with acute coronary syndrome. 1

Mechanism of Action

Ticagrelor belongs to the cyclopentyl-triazolopyrimidine class and works as a direct inhibitor of the P2Y12 receptor on platelets. Unlike clopidogrel, ticagrelor:

• Binds to the receptor at a location distinct from the ADP binding site
• Blocks ADP-mediated receptor activation in a noncompetitive fashion through an allosteric mechanism
• Does not require hepatic conversion to an active metabolite
• Has a rapid onset of action, achieving significant platelet inhibition within 30 minutes 1

Clinical Efficacy

The landmark PLATO trial demonstrated ticagrelor's superior efficacy compared to clopidogrel in 18,624 patients with acute coronary syndrome:

• Primary composite endpoint (cardiovascular death, MI, or stroke) was significantly reduced with ticagrelor (9.8% vs 11.7%, HR 0.84, p<0.001)
• Myocardial infarction rates were lower (5.8% vs 6.9%, p=0.005)
• Cardiovascular mortality was reduced (4.0% vs 5.1%, p<0.001)
• All-cause mortality was reduced (4.5% vs 5.9%, p<0.001) 1

Dosing Regimen

• Loading dose: 180 mg orally as a one-time dose
• Maintenance dose: 90 mg orally twice daily, typically for 12 months after an ACS event
• Concomitant therapy: Low-dose aspirin (75-100 mg daily) is recommended 2, 1

Clinical Applications

Ticagrelor is indicated for:

• Acute coronary syndromes (unstable angina, NSTEMI, STEMI)
• Patients managed with either invasive (PCI) or non-invasive strategies 1

Advantages Over Clopidogrel

• More rapid onset of action
• More potent platelet inhibition
• More consistent antiplatelet effect
• Reversible binding (vs. irreversible with clopidogrel)
• Reduced mortality in ACS patients 3, 4

Safety Considerations

• Bleeding risk: No significant difference in overall major bleeding compared to clopidogrel, but higher rates of non-CABG-related bleeding 1, 3
• Dyspnea: Occurs in up to 15% of patients, usually mild to moderate 2
• Bradycardia: May occur, often asymptomatic 2
• Perioperative management: Discontinue at least 5 days before planned surgery 2

Important Clinical Pearls

1. Drug interactions: Ticagrelor is metabolized by CYP3A4 and may increase exposure to simvastatin and lovastatin; atorvastatin is a safer statin choice 1

2. Switching from clopidogrel: When transitioning from clopidogrel to ticagrelor, a loading dose of ticagrelor should still be administered 2

3. Aspirin dosing caution: Higher aspirin doses (>100 mg daily) may reduce ticagrelor's effectiveness 2

4. Compliance importance: Patient adherence is especially critical with the twice-daily dosing regimen 2

5. European guidelines: The European Society of Cardiology recommends ticagrelor over clopidogrel for ACS patients unless there are contraindications (previous intracranial hemorrhage or ongoing bleeds) 1

Special Populations

In patients requiring oral anticoagulation who undergo PCI:

• Clopidogrel is generally preferred over ticagrelor for triple therapy to minimize bleeding risk
• However, in selected patients at high ischemic/thrombotic risk and low bleeding risk, ticagrelor may be considered 1

Ticagrelor represents a significant advancement in antiplatelet therapy, offering improved outcomes for patients with acute coronary syndrome compared to previous standard therapies.