title: The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease.
abstract: Recent studies suggest that cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiaggregatory effect of clopidogrel. We evaluated how CYP3A4 metabolized statins and non-CYP3A4 metabolized statins influence platelet aggregation when given concomitantly with clopidogrel. Sixty-six stable patients with ischemic heart disease were included in this parallel group study. All patients were on clopidogrel and aspirin. Thirty-three patients received a CYP3A4 metabolized statin (simvastatin or atorvastatin), and 33 were treated with a non-CYP3A4 metabolized statin (pravastatin). The antiplatelet effect of clopidogrel was assessed at inclusion and 21 days after statin discontinuation. Platelet function was evaluated by two methods 1) optical platelet aggregometry after stimulation with 20 and 30 microM ADP, and 2 and 4 mg/l collagen, respectively, 2) a Platelet FunctionAnalyzer-100. The primary effect measure was final platelet aggregation after stimulation with 20 microM ADP. No difference was observed between patients treated with a CYP3A4 metabolized statin and patients receiving a non-CYP3A4 metabolized statin (30% point (7-42) versus 20% point (9-32), p = 0.83). Platelet aggregation was not improved by discontinuation of statins for 21 days. Indeed, we found that statin treatment given concomitantly with clopidogrel resulted in an improved platelet inhibition when compared to clopidogrel given alone. The antiplatelet effect of clopidogrel is not attenuated by concomitant treatment with a CYP3A4 metabolized statin in patients with clinical stable ischemic heart disease.
authors.affiliation: Department of Cardiology, Odense University Hospital, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Vinholt
authors.forename: Tina Svenstrup
authors.initials: TS
authors.lastname: Poulsen
authors.forename: Lars
authors.initials: L
authors.lastname: Korsholm
authors.forename: Søren Risom
authors.initials: SR
authors.lastname: Kristensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
authors.forename: Hans
authors.initials: H
authors.lastname: Mickley
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects; D008078:Cholesterol, LDL; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006331:Heart Diseases / Q000097:blood* / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007511:Ischemia; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014945:Wound Healing
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; D000077144:Clopidogrel; D019821:Simvastatin; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017035:Pravastatin; D013988:Ticlopidine