title: Multiple antiplatelet effects of clopidogrel are not modulated by statin type in patients undergoing percutaneous coronary intervention.
abstract: We investigated whether statin type or dose influenced the inhibition of platelet function induced by clopidogrel in a prospective, open, parallel group study in patients undergoing elective percutaneous coronary intervention. Patients were taking CYP3A4 metabolised atorvastatin (n = 20) or simvastatin (n = 21), non-CYP3A4 metabolised pravastatin (n = 11) or fluvastatin (n = 2), or no statin therapy (n = 5). ADP and TRAP-induced platelet aggregation were measured using optical aggregometry, whole-blood single-platelet counting, and the Ultegra and Plateletworks point-of-care systems. Platelet pro-coagulant activity (annexin V binding and microparticle formation), P-selectin expression and platelet-leukocyte conjugate formation were assessed by flow cytometry. Platelet responses were measured at baseline, 4 h post clopidogrel 300 mg, and after 10 and 28 days with clopidogrel 75 mg daily. Clopidogrel significantly inhibited both ADP and TRAP-induced platelet responses over time, with steady state inhibition achieved by day 10. This was demonstrated by all techniques used. There was no significant effect of statin type or dose on platelet responses by any method at any time-point. In conclusion, statins do not influence the inhibitory effects of clopidogrel on multiple platelet responses, including aggregation, P-selectin expression, platelet-leucocyte conjugate formation and pro-coagulant responses, in patients undergoing elective PCI.
authors.affiliation: Cardiovascular Research Group, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Sheffield, UK.
authors.forename: Simon M G
authors.initials: SM
authors.lastname: Smith
authors.forename: Heather M
authors.initials: HM
authors.lastname: Judge
authors.forename: Gary
authors.initials: G
authors.lastname: Peters
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy; D004341:Drug Evaluation; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000077340:Fluvastatin; D000069059:Atorvastatin; D000077144:Clopidogrel; D019821:Simvastatin; D017035:Pravastatin; D013988:Ticlopidine