Influence of statin treatment on platelet inhibition by clopidogrel – a randomized comparison of rosuvastatin,atorvastatin and simvastatin co‐treatment

Objectives. 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 μmol 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.