Unmet needs in oral antiplatelet therapy with ADP receptor blocking agents.
Antiplatelet agents like aspirin and clopidogrel are treatment cornerstones for acute coronary syndromes (ACS). Drawbacks of dual therapy with these agents include slow onset and offset of effect and wide response variability. Clopidogrel may provide little benefit if administered too close to percutaneous coronary intervention (PCI) and increase major bleeding risk if given too close to coronary artery bypass grafting (CABG) or other surgery. It may not provide sufficient antiplatelet coverage prior to CABG if stopped too long before intervention and leave patients without antiplatelet coverage due to hyporesponsiveness. Prasugrel has made steps towards addressing these limitations by exhibiting more efficient metabolism, more rapid onset of effect, and greater and more consistent platelet inhibition than clopidogrel. The TRITON-TIMI38 trial in ACS patients undergoing PCI showed prasugrel produced greater ischemic event protection than clopidogrel but significantly increased major bleeding risk. AZD6140, the first reversible oral P2Y(12) inhibitor, provides more rapid onset of effect and greater and more consistent platelet inhibition than clopidogrel. In DISPERSE2, a phase II trial in ACS patients, AZD6140 did not increase bleeding risk, reduced bleeding risk among CABG patients, and produced numerical reductions in myocardial infarction risk. AZD6140 is being compared with clopidogrel in PLATO, a phase III trial in approximately 18000 ACS patients.
Husted
Steen
S
Department of Medicine and Cardiology, Arhus University Hospital, DK-8000 Arhus C, Arhus, Denmark. steen.husted@as.aaa.dk
D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000503:physiopathology; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000284:Administration, Oral; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine