Hepatotoxicity of combined therapy of atorvastatin with platelet P2Y[12]-ADP receptor antagonist in coronary heart disease treated patients

ABSTRACT

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in coronary disease and percutaneous coronary stenting. It appears to be a safe drug with few occurrences of liver side-effects that usually resolved after drug withdrawal. The goal of this study was to investigate whether the co-administration of atorvastatin could aggravate the hepatic - toxicity of clopidogrel. Eighty patients with coronary disease were included in this study. All patients received a dose of 75 mg/day of clopidogrel. Forty patients group A with recent treatment [< 3 months] of clopidogrel; other forty patients group B with [> 1 year] treatment of clopidogrel. Liver function tests were measured and studied at baseline [clopidogrel without atorvastatin] and at 2, 4, 6 weeks of clopidogrel with atorvastatin [40 mg/day] afterwards. Liver function tests with co-therapy showed high significant elevation in mean serum total alkaline phosphatase [P<0.001], significant decrease [P< 0.05] in mean serum gamma-glutamyl transferase ,significant elevation [P< 0.05] in mean serum direct bilirubin and insignificant elevation [P>0.05] in mean serum total bilirubin, whereas the results appeared within normal range in mean serum levels of alanine aminotransferase, aspartate aminotransferase ,glutamate dehydrogenase -1,and total protein. Combination of atorvastatin and clopidogrel may induce hepatic injury cholestatic type resulting from abnormal bile flow caused by either drugs or its metabolites