Ticlopidine with Ginkgo Biloba extract: A Feasible Combination for Patients with Acute Cerebral Ischemia

Abstract

Background: Even though clopidogrel is the most used drug for cardiovascular prevention, resistance occurs in significant numbers. Therefore, we evaluated platelet aggregation ability of thienopyridines in relation with various genotypes. Method: The study population was randomly assigned with clopidogrel (n=43), ticlopidine (n=41), or ticlopidine plus Gingko Biloba extract (EGb) (n=43). Dosage was maintained as 75 mg clopidogrel daily, 250 mg ticlopidine twice daily, and 250 mg ticlopidine plus 80 mg Gingko Biloba extract twice daily. Using multiple electrodes aggregometry, platelet aggregation was measured by activators of adenosine diphosphate (ADP), arachidonic acid (ASP), and thrombin (TRAP) at baseline (T0), 7 days (T1), and 90 days (T2). Side-effects were analyzed in the 3 groups. Inhibition of platelet aggregation (IPA) was defined as percent decrease at T0 and T1. Non-responsiveness (<IPA 20%) was analyzed according to cytochrome P450 polymorphisms. Results: There was no difference of general demographics and platelet aggregation at baseline in all groups. A significant difference of platelet aggregation showed on ADP test in the groups at T1 (28.9 +/- 17.2 vs. 22.7 +/- 11.1 vs. 14.6 +/- 10.3%, p<0.001) and T2 (27.5 +/- 24.5 vs. 18.3 +/- 16.6 vs. 14.4 +/- 9.8%, p=0.007), whereas ASP (p=0.064) and TRAP tests (p=0.143) had no differences at T1. Serious adverse events had no differences among the groups (p=0.902). CYP2C19*2 alleles had poor responsiveness of clopidogrel (p=0.038), and not in ticlopidine (p=0.780). Conclusions: This finding suggests that ticlopidine plus Gingko Biloba extract has sufficient anti-platelet abilities with an acceptable profile of adverse events and CYP2C19*2 alleles are associated with clopidogrel responsiveness. Published by Elsevier Ltd.