Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2008

Current guidelines recommend dual antiplatelet of aspirin and clopidogrel for patients who have acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) those patients commonly prescribed proton pump inhibitors (PPIs) to prevent gastrointestinal side effects. The purposes of this study were to determine the effect of rabeprazole and omeprazole on the antiplatelet action of clopidogrel plus aspirin, to investigate the prevalence of clopidogrel nonresponder in patients with coronary artery disease (CAD) and compare the rate of clopidogrel nonresponsiveness before and after receiving each PPI. All consecutive patients with angiographic diagnosis of CAD were recruited. The study consisted of patients who had taken clopidogrel 75 mg/day at least 5 days and patients who received loading dose (LD) of clopidogrel 300 mg and aspirin 300-325 mg before underwent PCI. All patients were treated with aspirin 81-325 mg/day at least 7 days prior to the study. Exclusion criteria included previous treatment with PPIs within 2 weeks and serum creatinine > 1.5 mg/dl. The patients were randomized into two treatment groups: 20 mg/day of omeprazole or 20 mg/day of rabeprazole for at least 2 weeks. Effect of clopidogrel on platelet aggregation was measured by light transmission aggregometry using ADP 20 M as agonist. Clopidogrel nonresponder was defined as ADP 20 M-induced maximal platelet aggregation (MPA) > 50%. Platelet aggregation test was assessed before and after receiving PPIs for at least 2 weeks. Of 87 patients were enrolled during August 2008 to March 2009, 43 patients took omeprazole while 44 patients took rabeprazole. Overall, 18% were scheduled for elective PCI patients and 82% were stable CAD patients. This study found that concomitant use of omeprazole or rabeprazole in patients receiving aspirin plus clopidogrel were significantly increased platelet aggregation from baseline (32.5% and 14%, respectively) but not significantly different between the two drugs (p = 0.519). Average values of MPA after ADP 20 M stimuli before and after receiving PPIs were 38.53 +- 20.16% and 52.05 +- 19.46%, respectively. There was no significant difference in demographic, clinical characteristics and co-medications between the two groups except for body mass index. This study found high prevalence of clopidogrel nonresponder, 34%, prior to taking PPIs and increased to 59% after receiving PPIs in CAD patients. Univariate analysis, showed that diabetes mellitus to be a risk factor for clopidogrel nonresponsiveness (OR = 2.93, 95%CI = 1.17-7.29, p = 0.019).