Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study.
BACKGROUND
Some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to address this issue prospectively by performing serial measurements of 19 platelet characteristics using conventional aggregometry, rapid analyzers, and flow cytometry.


METHODS
The Interaction of Atorvastatin and Clopidogrel Study (Interaction Study) was designed for patients undergoing coronary stenting. All patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg of clopidogrel immediately prior to stent implantation. They had been taking atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at least 30 days prior to stenting. The main outcome measure was comparison of platelet biomarkers 4 and 24 hours after clopidogrel administration between study groups.


RESULTS
At baseline, patients from both statin groups exhibited diminished platelet aggregation and reduced platelet expression of G-protein-coupled protease-activated thrombin receptor (PAR)-1. There were no significant differences in measured platelet characteristics among the study groups 4 and 24 hours after clopidogrel intake, with the exception of a lower collagen-induced aggregation at 24 hours and a constantly diminished expression of PAR-1 in patients treated with any statin.


CONCLUSIONS
Statins in general, and atorvastatin in particular, do not affect the ability of clopidogrel to inhibit platelet function in patients undergoing coronary stenting. These prospective data also suggest that statins may inhibit platelets directly via yet unknown mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.
Serebruany
Victor L
VL
HeartDrug Research, LLC, Baltimore, MD, USA. Heartdrug@aol.com
Midei
Mark G
MG
Malinin
Alex I
AI
Oshrine
Benjamin R
BR
Lowry
David R
DR
Sane
David C
DC
Tanguay
Jean-François
JF
Steinhubl
Steven R
SR
Berger
Peter B
PB
O'Connor
Christopher M
CM
Hennekens
Charles H
CH
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D019917:Blood Vessel Prosthesis Implantation; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000628:therapy; D004347:Drug Interactions; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine