Antiplatelet Therapy

Introduction to Ticagrelor

• Ticagrelor is a direct-acting, reversible P2Y12 receptor antagonist that does not require hepatic bioactivation, according to the American College of Cardiology 1, 2
• It has a half-life of approximately 7 hours, and its active metabolite has a half-life of about 8.5 hours, which is relevant for perioperative management 2, 3

Pharmacokinetics and Pharmacodynamics

• Ticagrelor acts directly on the P2Y12 receptor and binds reversibly, unlike thienopyridines such as clopidogrel and prasugrel which irreversibly inhibit platelet function, according to the American College of Cardiology guidelines 2, 4
• The following table compares the mechanisms, reversibility, and recovery times of ticagrelor, clopidogrel, and prasugrel:

2, 4

Perioperative Management

• The American College of Cardiology recommends discontinuing ticagrelor 3-5 days before elective procedures to minimize bleeding risk, as also suggested by the American College of Chest Physicians 5, 2
• Platelet function begins returning within 3-5 days after discontinuation of ticagrelor, compared to 5 days for clopidogrel and 7 days for prasugrel, as recommended by the American Heart Association 4
• Platelet transfusions are largely ineffective in reversing ticagrelor's effects if administered within 24 hours of the last dose, according to the American Society of Hematology 2
• Administering tranexamic acid may reduce bleeding, and local hemostatic measures appropriate to the bleeding site should be considered 2
• A specific monoclonal antibody fragment, bentracimab (PB2452), is in advanced development and has shown promising results in clinical trials, providing immediate and sustained reversal of ticagrelor's antiplatelet effects 6

Management of Bleeding and Reversal

• Delay surgery for at least 3-5 days after the last ticagrelor dose, if possible, to minimize bleeding risk 7
• Avoid relying on platelet transfusion alone, as it fails to restore ADP-induced platelet aggregation in ticagrelor-treated patients, and avoid administering desmopressin due to disappointing clinical results 2
• Avoid bridging with heparins, as they do not reduce stent thrombosis risk but may increase bleeding risk 7
• Monitor for rebound thrombotic events and consider the timing of restarting antiplatelet therapy based on thrombotic risk 7

Clinical Use and Dosing

• The American College of Cardiology/American Heart Association guidelines recommend ticagrelor in preference to clopidogrel for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with either an early invasive or ischemia-guided strategy 8
• Administer ticagrelor loading dose of 180 mg regardless of timing of last clopidogrel dose, and begin maintenance dose of ticagrelor 90 mg twice daily 8
• Adjust aspirin dose to 81 mg daily when used with ticagrelor, as higher aspirin doses (>100 mg) may reduce ticagrelor's effectiveness 8, 9, 10
• Emphasize the importance of twice-daily dosing with ticagrelor and educate patient that missing doses significantly increases thrombotic risk 8
• If a dose of ticagrelor is missed and remembered within 12 hours of the usual time, the missed dose should be taken immediately, and the regular twice-daily schedule should be resumed 9

Safety and Side Effects

• Contraindications for ticagrelor include previous intracranial hemorrhage or ongoing bleeds, and patients with a history of stroke or transient ischemic attack (TIA) should be aware that ticagrelor increases the risk of intracranial hemorrhage compared to clopidogrel 11, 10
• Side effects of ticagrelor include potential dyspnea, which occurs in up to 15% of patients 8
• Patients should have a clear plan for what to do if a dose is missed, and should be aware of the symptoms of thrombotic events, such as chest pain or shortness of breath, which should prompt immediate medical attention 9