Influence of statin treatment on platelet inhibition by clopidogrel - a randomized comparison of rosuvastatin, atorvastatin and simvastatin co-treatment.
OBJECTIVE
Possible interactions between clopidogrel and atorvastatin, simvastatin or rosuvastatin (a 'non-CYP3A4' metabolized statin) were investigated in a randomized prospective study using sensitive and specific ex vivo platelet function tests.


METHODS
Patients with coronary artery disease participating in a double-blind study comparing lipid-lowering effects of atorvastatin (20-80 mg OD; n = 22) and rosuvastatin (10-40 mg OD; n = 24) were studied before and after 2 weeks treatment with clopidogrel 75 mg OD after completed statin dose titration. In addition, 23 patients were randomized to open-label simvastatin 40 mg OD.


RESULTS
Clopidogrel inhibited 10 mumol L(-1) ADP-induced platelet aggregation by 40 +/- 27%, 57 +/- 28% and 51 +/- 29%, respectively, in patients on rosuvastatin, atorvastatin and simvastatin treatment. The other platelet tests yielded similar results. No dose-dependent effects of rosuvastatin or atorvastatin co-treatment on clopidogrel efficacy were observed.


CONCLUSIONS
Treatment with CYP3A4 metabolized statins, atorvastatin or simvastatin, did not attenuate the platelet inhibitory effect of clopidogrel maintenance treatment compared with the non-CYP3A4 metabolized, rosuvastatin.
Malmström
Rickard E
RE
Clinical Pharmacology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden. rickard.malmstrom@ki.se
Ostergren
J
J
Jørgensen
L
L
Hjemdahl
P
P
D000368:Aged; D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; D000077144:Clopidogrel; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; D013988:Ticlopidine