The inhibitory potency of clopidogrel on ADP-induced platelet activation is not attenuated when it is co-administered with atorvastatin (20 mg/day) for 5 weeks in patients with acute coronary syndromes.
The antiplatelet potency of clopidogrel may be attenuated by short-term co-administration of lipophilic statins metabolized through the cytochrome P-450, isoform 3A4. We investigated whether the co-administration of atorvastatin (20?mg/day) for 5 weeks, in patients with acute coronary syndromes (ACS) could affect the antiplatelet activity of clopidogrel. Fifty-one patients with the first episode of an ACS were included in the study. All patients underwent percutaneous coronary intervention (PCI) and received a loading dose of 375 mg of clopidogrel, followed by 75 mg/day for at least 3 months. Twenty-six of them presented with low density lipoprotein (LDL) cholesterol levels >100?mg/dl (2.6 mmol/l) (measured within 24 h from the onset of symptoms) and received daily 20 mg/day of atorvastatin. The ADP- or TRAP-induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 min after admission) and 5 weeks afterwards. Atorvastatin did not influence either the clopidogrel-induced inhibition of platelet aggregation initiated by 5 or 10 microM ADP or the clopidogrel-induced reduction of the membrane expression of P-selectin and CD40L induced by ADP. In conclusion, atorvastatin, even at a dose of 20 mg/day does not affect the antiplatelet efficacy of clopidogrel when co-administered for 5 weeks in ACS patients.
Mitsios
John V
JV
Laboratory of Biochemistry, Department of Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Papathanasiou
Athanasios I
AI
Elisaf
Moses
M
Goudevenos
John A
JA
Tselepis
Alexandros D
AD
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D014280:Triglycerides; C072032:thrombin receptor peptide (42-55); D023201:CD40 Ligand; D000244:Adenosine Diphosphate; D002784:Cholesterol; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine