ranitidin versus omeprazole in patients taking clopidogrel

Conditions: Coronary Artery Disease; Drug Interaction Potentiation

Summary: previous reports have shown a possible drug interaction between clopidogrel and proton pump inhibitors (ppi´s), which could result in increased number of adverse cardiovascular events among patients on dual antiplatelet therapy(dapt). because of this, ranitidin has been proposed as an alternative drug to ppi´s for prophylaxis of gastrointestinal bleeding in patients who need dapt. the study´s aim is to test the hypothesis that ranitidin doesn´t have any influence on clopidogrel pharmacodynamic.

study population: 100 patients with stable coronary artery disease from heart institute inclusion criteria: * age \> 18 years old * coronary artery disease, defined as previous myocardial infarction and/or coronary angioplasty and/or coronary artery bypass graft (cabg) surgery and/or coronariography showing obstruction of at least 50 % in one of major epicardial vessels * treatment with acetylsalicylic acid (asa) 100 mg/day exclusion criteria: * use in the last 7 days of oral anticoagulant or any other antiplatelet drug beside asa * previous utilization of ppi or ranitidine in the last 7 days before randomization * active bleeding * pregnancy or woman of childbearing age without contraceptive method * hemoglobin \ 50 %, platelets \ 500.000/mm3; creatinin clearance \< 50 ml/minute * percutaneous coronary intervention (pci) on the last 30 days before randomization (or pci on the last year when drug-eluted stents are used); cabg surgery on the last 90 days; acute coronary syndrome on the last 60 days * active malignant neoplasm * active peptic ulcer disease on the last 60 days or upper gastrointestinal bleeding any time in life * known allergy to the drugs clopidogrel, ranitidine or omeprazole * refuse to participate in the study\] methodology: the study has a double-blind, double-dummy prospective design. clopidogrel action is evaluated by platelet function tests: verifynow, bioimpedance aggregometry and platelet function analyzer-100 (pfa-100). the patients have measurements of platelet function on three moments: before starting clopidogrel; 1 week after dapt with clopidogrel (without loading dose) plus asa; and after 1 week of randomization to ranitidin 150 mg bid or omeprazole 20 mg bid.

Eligibility criteria:
inclusion criteria: * age \> 18 years old * coronary artery disease, defined as previous myocardial infarction and/or coronary angioplasty and/or cabg surgery and/or coronariography showing obstruction of at least 50 % in one of major epicardial vessels * treatment with acetylsalicylic acid (asa) 100 mg/day exclusion criteria: * use on the last 7 days of any other antiplatelet drug beside asa or oral anticoagulant * previous utilization of ppi or ranitidine in the last 7 days before randomization * any active bleeding * pregnancy or woman of childbearing age without contraceptive method * hemoglobin \ 50 %, platelets \ 500.000/mm3; creatinin clearance \< 50 ml/minute * percutaneous coronary intervention (pci) on the last 30 days before randomization (or pci on the last year when drug-eluted stents are used); cabg surgery on the last 90 days; acute coronary syndrome on the last 60 days * active malignant neoplasm * active peptic ulcer disease on the last 60 days or upper gastrointestinal bleeding any time in life * known allergy to the drugs clopidogrel, ranitidine or omeprazole * refuse to participate in the study

Keywords: clopidogrel omeprazole ranitidin interaction aggregability