title: ADP induced platelet degranulation in healthy individuals is reduced by clopidogrel after pretreatment with atorvastatin.
abstract: Statins inhibit platelet reactivity and reduce blood thrombogenicity. The effectiveness of clopidogrel in inhibiting platelet reactivity was suggested to be reduced in the presence of atorvastatin due to shared enzymes in metabolism. Healthy individuals, 17 pretreated with atorvastatin (20 mg/d for 3 days) and 17 without pretreatment, as well as 15 patients with stable coronary artery disease (CAD) and concurrent atorvastatin therapy were started on clopidogrel (loading dose 300 mg, then 75 mg/d). P-selectin on platelet surface after stimulation with ADP or Thrombin Receptor Activating Peptide (TRAP) was flow cytometrically measured before and during clopidogrel administration. Whole blood platelet agglutination was tested by a platelet function assay.TRAP and - in trend - ADP induced p-selectin exposure was reduced by the atorvastatin pretreatment before clopidogrel was added. Combining clopidogrel with atorvastatin in the healthy individuals led to a further reduction in ADP-induced platelet p-selectin exposure. Clopidogrel also reduced platelet reactivity in CAD patients with concurrent atorvastatin medication. We conclude that pretreatment with atorvastatin reduces platelet reactivity before administration of clopidgrel. No drug interaction was seen, however, platelet inhibitory effects were observed during the treatment with clopidogrel and atorvastatin.
authors.affiliation: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin Department of Internal Medicine / Cardiology Hindenburgdamm 30 12200 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Piorkowski
authors.forename: Ulf
authors.initials: U
authors.lastname: Weikert
authors.forename: Peter-Lothar
authors.initials: PL
authors.lastname: Schwimmbeck
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000069059:Atorvastatin; D015550:Cell Degranulation / Q000187:drug effects*; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005340:Fibrinogen / Q000378:metabolism; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011758:Pyrroles / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D006538:Heptanoic Acids; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine