Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease.
We compared the antiplatelet effects of clopidogrel and the intravenous platelet P2Y(12) receptor antagonist AR-C69931MX, which acts on the same receptor as clopidogrel by a different and reversible mechanism and, unlike clopidogrel, is active in vitro. Thirteen patients with acute coronary syndromes entered into a phase II study of intravenous AR-C69931MX (Group 1) and eight patients undergoing intracoronary stent implantation and treated with clopidogrel (Group 2) were studied using a whole blood single-platelet counting aggregation assay. Group 2 patients were also studied using turbidimetry with ADP and TRAP as agonists and whole blood [(14)C]5HT release to study dense granule secretion in response to ADP, collagen and TRAP. In Group 2 studies, a therapeutic concentration of AR-C69931MX was added in vitro before and after clopidogrel administration. AR-C69931MX in Group 1 achieved greater inhibition of ADP-induced platelet aggregation than clopidogrel in Group 2 and AR-C69931MX in vitro added to the effects of clopidogrel on ADP-induced aggregation. AR-C69931MX but not clopidogrel inhibited TRAP-induced aggregation and granule secretion and AR-C69931MX had a more consistent inhibitory effect on collagen-induced responses. In conclusion, therapeutic administration of clopidogrel moderately inhibits platelet P2Y(12) receptor activation and substantially greater P2Y(12) receptor blockade can be achieved with AR-C69931MX.
Storey
Robert F
RF
Cardiovascular Medicine, University Hospital, Queen's Medical Centre, Nottingham, NG7 2UH, UK. r.f.storey@sheffield.ac.uk
Wilcox
Robert G
RG
Heptinstall
Stan
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests; D058919:Purinergic P2 Receptor Antagonists; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine