Ticagrelor

摘要

Antiplatelet drugs are the cornerstone of treatment for patients with acute coronary syndromes (ACS) who undergo percutaneous coronary intervention. Clopidogrel and aspirin improve long-term clinical outcomes in these patients and have become a standard of care. However, many patients still experience ischemic/thrombotic events, and it appears that insufficient response to both aspirin and clopidogrel contribute to this failure. Clopidogrel is a prodrug that is metabolized in the liver to its active form. It inhibits platelet aggregation induced by adenosine diphosphate (ADP) by irreversibly binding to the ADP purinergic receptor (P2Y12) on the platelet surface. Prasugrel, a novel thienopyridine, exhibits more potent antiplatelet effects with lower interpatient variability and more rapid onsetof activity. All thienopyridines, however, have pharmacological limitations, which have fueled the search for more effective non-thienopyridine P2Y12 inhibitors. Promising results have been reported with ticagrelor, the first oral P2Y12 receptor antagonist with reversible effects. Ticagrelor does not require metabolic activation. In vivo one active metabolite is formed whose potency and pharmacokinetic properties are very similar to those of the parent compound, but it probably plays a minor role in ticagrelor’s antiplatelet effects. Ticagrelor offers more rapid and more pronounced platelet inhibition than other antiplatelet agents. Furthermore, the reversibility of its effects may allow shorter periods of suspension of antiplatelet treatment prior to surgery, reducing the risk of perioperative thrombotic and hemorrhagic events. Preliminary results show a trend toward protection from coronary events and no increased risk for major bleeding compared with clopidogrel. Further investigation is needed, however, to determine the optimal dosage for minimizing bleeding risks and to evaluate its impact on outcomes in various subsets of ACS patients.