title: Ticagrelor: from discovery to Phase III clinical trial.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D017326:Clinical Trials, Phase III as Topic; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine