Platelet ADP-receptor antagonists for cardiovascular disease: past, present and future.
Aspirin is the foundation antiplatelet therapy for patients at risk of cardiovascular events. The thienopyridine, clopidogrel, is modestly more effective than aspirin and in patients with stroke seems to be as effective as the combination of aspirin and dipyridamole. The addition of clopidogrel to aspirin further reduces the risk of cardiovascular events in patients with acute coronary syndromes and those who undergo percutaneous coronary intervention, but uncertainty remains about whether this combination has incremental efficacy over clopidogrel monotherapy in patients with stroke or peripheral arterial disease. Clopidogrel has pharmacological limitations that have prompted the search for more effective ADP-receptor antagonists. Promising results have been achieved with the thienopyridine, prasugrel, which has been compared with clopidogrel in patients treated with aspirin. The nonthienopyridine P2Y(12) inhibitors AZD6140 and cangrelor are presently being evaluated in phase III, randomized, controlled trials.
Raju
Nina C
NC
Thrombosis Service, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L2X2, Canada. nraju1@cogeco.ca
Eikelboom
John W
JW
Hirsh
Jack
J
D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000627:therapeutic use; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000097:blood; D058925:Receptors, Purinergic P2Y12; D015607:Stents; D013876:Thiophenes / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
C548576:P2RY12 protein, human; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin