What is ticagrelor?

What is Ticagrelor?

Ticagrelor is an oral, reversible P2Y12 receptor inhibitor that directly blocks adenosine diphosphate (ADP)-mediated platelet activation, providing more rapid and potent antiplatelet effects than clopidogrel for patients with acute coronary syndromes. 1

Mechanism of Action

• Ticagrelor belongs to the cyclopentyl-triazolopyrimidine class and acts as a direct, reversible inhibitor of the P2Y12 receptor 1
• It binds to the P2Y12 receptor at a site distinct from the ADP binding site, blocking receptor activation through a noncompetitive, allosteric mechanism 1
• Unlike clopidogrel and prasugrel (thienopyridines), ticagrelor does not require hepatic conversion to an active metabolite 1

Pharmacokinetic Profile

• Ticagrelor achieves platelet inhibition within 30 minutes, exceeding levels obtained with 300-600 mg clopidogrel loading doses 1, 2
• Peak inhibitory effect occurs approximately 2 hours after a loading dose of 180 mg or maintenance dose of 90 mg twice daily 1
• The reversible binding allows platelet function to recover within 3-4 days after discontinuation, compared to 5-10 days with irreversible thienopyridines 1
• Ticagrelor has a plasma half-life of approximately 12 hours, necessitating twice-daily dosing 2

Standard Dosing

• Loading dose: 180 mg (not 90 mg) 1, 2
• Maintenance dose: 90 mg twice daily 1
• A 60 mg twice daily maintenance dose exists for extended therapy beyond 12 months but was not studied immediately post-PCI 1

Clinical Efficacy Evidence

• In the PLATO trial of 18,624 patients with acute coronary syndromes, ticagrelor reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke by 16% compared to clopidogrel (9.8% vs 11.7%, HR 0.84, P<0.001) 3
• Ticagrelor reduced all-cause mortality (4.5% vs 5.9%, P<0.001) and stent thrombosis more effectively than clopidogrel 3, 4
• Myocardial infarction rates were lower with ticagrelor (5.8% vs 6.9%, P=0.005) 3
• Benefits were consistent in both invasively and non-invasively managed patients 5

Bleeding Risk Profile

• Major bleeding rates were similar between ticagrelor and clopidogrel (11.6% vs 11.2%, P=0.43) 3
• Non-CABG-related major bleeding was higher with ticagrelor (4.5% vs 3.8%, P=0.03) 3, 4
• Ticagrelor had more fatal intracranial bleeding but fewer fatal bleeds of other types compared to clopidogrel 3

Unique Adverse Effects

• Dyspnea occurs in 10-15% of patients, typically within the first week of treatment, usually mild to moderate in severity 4, 5
• Ventricular pauses ≥3 seconds may occur but are largely asymptomatic 4, 5
• These side effects are not seen with clopidogrel 4

Clinical Positioning

The ACC/AHA recommends ticagrelor over clopidogrel for patients with acute coronary syndromes based on superior reduction in cardiovascular outcomes (Class IIa recommendation) 4

When to Use Ticagrelor:

• Patients with acute coronary syndromes (NSTE-ACS or STEMI) 1
• High ischemic/thrombotic risk patients with low bleeding risk 1
• Patients undergoing PCI for acute coronary syndromes 1

When to Use Clopidogrel Instead:

• Prior stroke or transient ischemic attack 4
• High bleeding risk patients 1, 4
• Contraindications or intolerance to ticagrelor 4
• When ticagrelor is unavailable 4
• Patients with atrial fibrillation on oral anticoagulation undergoing PCI (clopidogrel preferred due to lower bleeding risk) 1

Important Clinical Considerations

• Aspirin dose should not exceed 75-100 mg daily when used with ticagrelor, as higher doses may reduce ticagrelor's efficacy 1, 2
• Discontinue ticagrelor 5 days before elective surgery 1, 2
• Ticagrelor is a P-glycoprotein inhibitor and can increase levels of concomitant medications like dabigatran 2
• In patients with atrial fibrillation on oral anticoagulation, avoid triple therapy (aspirin + ticagrelor + anticoagulant); use double therapy (ticagrelor + anticoagulant without aspirin) 1