Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes.
BACKGROUND
The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins. We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes (ACS) could affect the antiplatelet potency of clopidogrel.


RESULTS
Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study. Patients were randomized to receive daily either 10 mg of atorvastatin (n=21) or 40 mg of pravastatin (n=24). Thirty patients who underwent percutaneous coronary intervention (PCI) received a loading dose of 375 mg of clopidogrel, followed by 75 mg/d for at least 3 months. In the remaining 15 patients who refused to undergo PCI, clopidogrel therapy was not administered. Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel. The serum levels of soluble CD40L and the adenosine 5'-diphosphate- or thrombin receptor activating peptide-14-induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 minutes after admission) and 5 weeks later. Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation, nor did clopidogrel influence the therapeutic efficacy of atorvastatin.


CONCLUSIONS
Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients.
Mitsios
John V
JV
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece.
Papathanasiou
Athanasios I
AI
Rodis
Foteini I
FI
Elisaf
Moses
M
Goudevenos
John A
JA
Tselepis
Alexandros D
AD
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000069059:Atorvastatin; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; C072032:thrombin receptor peptide (42-55); D023201:CD40 Ligand; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; D000077144:Clopidogrel; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D017035:Pravastatin; D013988:Ticlopidine