P2Y12 antagonism: promises and challenges.
The P2Y12 antagonist clopidogrel has a well-established role as an antithrombotic agent in the settings of percutaneous coronary intervention and acute coronary syndromes. However, several challenges remain, including the relatively slow onset of action of clopidogrel and the phenomenon of clopidogrel response variability or "resistance". Novel P2Y12 antagonists, including prasugrel, AZD6140, and cangrelor, have a faster onset of action, as well as more potent, and less variable, inhibition of platelet function ex vivo. Whether this promise will be translated into clinical benefit for patients will be determined by the results of ongoing phase 3 clinical trials.
Michelson
Alan D
AD
Center for Platelet Function Studies, University of Massachusetts Medical School, Room S5-846, 55 Lake Avenue North, Worcester, MA 01655, USA. michelson@platelets.org
D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality* / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D017326:Clinical Trials, Phase III as Topic; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004502:Education, Medical, Continuing; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D058919:Purinergic P2 Receptor Antagonists; D016032:Randomized Controlled Trials as Topic; D058925:Receptors, Purinergic P2Y12; D018570:Risk Assessment; D016019:Survival Analysis; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D008565:Membrane Proteins; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine