Ticagrelor: From discovery to Phase III clinical trial

摘要

Ticagrelor (AZD6140), a cyclopentyl-triazolo-pyrimidine, is the first orally available antagonist of the ADP receptor of the P2Y12 subtype. Ticagrelor inhibits platelets in a reversible manner and does not require hepatic bioactivation. The pharmacology of ticagrelor indicates that it provides more consistent, more rapid and more potent platelet inhibition than clopidogrel. Preclinical and clinical studies with ticagrelor have demonstrated that this drug has excellent oral bioavailability. The Phase III clinical study of Platelet Inhibition and Patient Outcomes (PLATO) has shown that ticagrelor reduced ischemic events and all-cause mortality without an increase in major bleeding complications. Potential advantages of ticagrelor include more flexibility in its use if rapid onset of action is needed before percutaneous coronary interventions or when cessation is required before coronary artery bypass graft surgery. Potential disadvantages include more side effects such as dyspnea, ventricular pauses or an increase in concentrations of uric acid and creatinine. However, ticagrelor did not only reduce death due to vascular causes but also all-cause mortality. Further clinical trials in indications other than acute coronary syndrome are awaited.