Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

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 \< 10 g/dL or hematocrit \< 30 %, hematocrit \> 50 %, platelets \< 100.000/mm3 or \> 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 \< 10 g/dL or hematocrit \< 30 %, hematocrit \> 50 %, platelets \< 100.000/mm3 or \> 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