Hepatotoxicity of Combined Therapy of Atorvastatin with Platelet P2Y12-ADP Receptor Antagonist in Coronary Heart Disease Treated Patients


ABSTRACT : BACKGROUND: 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.OBJECTIVE: The goal of this study was to investigate whether the co-administration of atorvastatin could aggravate the hepatic - toxicity of clopidogrel.PATIENTS AND METHODS: 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.RESULTS: 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 .CONCLUSION: Combination of atorvastatin and clopidogrel may induce hepatic injury cholestatic type resulting from abnormal bile flow caused by either drugs or its metabolites.KEYWORDS: clopidogrel; atorvastatin; liver function tests.