Effects of the atorvastatin and clopidogrel combination therapy on statin bioavailability and platelet function of patients with stable coronary disease

Abstract

BACKGROUND: Atorvastatin 80 mg is recommended in patients with coronary artery disease to reduce cardiovascular events, however, there is controversy regarding the pharmacokinetic interactions between high doses of statins and the concomitant use of clopidogrel, since they share the same biotransformation pathway. This study evaluated the effects of the atorvastatin/clopidogrel combination therapy on the pharmacokinetics of statins and on platelet function of patients with stable coronary artery disease receiving chronic statins METHOD: Patients were admitted four times (V1 to V4) to a day-clinic. Statin was discontinued seven days (D) before the first admission. Patients then received atorvastatin 80 mg (D1 to D22) and clopidogrel 75 mg/day (D8 to D29). Fasting blood samples were obtained at all time points for lipid measurements, platelet function tests (cone and plate technique), and quantification of atorvastatin plasma levels (liquid chromatography and mass spectrometry) RESULTS: The discontinuation of statins for one week changed the lipid profile (P V2, V3 and V4). Platelet adhesion was lower with clopidogrel alone (P = 0.003; V4 V2, V3 e V4). A adesão plaquetária foi menor com clopidogrel isolado (P = 0,003; V4 < V1, V2 e V3), enquanto para a agregação houve menor valor com tratamento combinado atorvastatina/clopidogrel ou clopidogrel isolado comparado aos demais períodos (P < 0,0001; V3 e V4 < V1 e V2). O clopidogrel não modificou as concentrações de atorvastatina CONCLUSÃO: Atorvastatina em alta dose não afetou as respostas plaquetárias ao clopidogrel; entretanto, curto período de suspensão da estatina piorou o perfil lipídico e a função plaquetária.Universidade Federal de São Paulo (UNIFESP)Instituto GalenoUNIFESPSciEL