NSAIDs vs. Coxibs in the Presence of Aspirin

Eligibility Criteria

• 1. Age 18-75 years of age for patients who regularly use NSAIDs.
• 2. Age 18-65 years of age for patients who do not regularly use NSAIDs
• 3. Able to give informed consent
• 4. Subjects with CVD or increased CV risk. Please see definitions for each criteria below:
• * Increased CV risk (Subjects should have at least 3 of the following)
• * \> 55 years of age
• * Hypertension
• * Dyslipidemia (LDL \> 160 mg/dL or HDL \< 40 mg/dL in females and \< 35 mg/dL in males or subjects currently receiving lipid lowering therapy as standard of care (i.e. statin drugs, prescription ω 3-acid ethyl esters, fibrates or prescription niacin \[≥1,000 mg/d\])
• * Family history of premature CV disease (MI, angina pectoris, heart failure, cardiac death or coronary revascularization, stroke, carotid endarterectomy, or other arterial surgery or angioplasty for atherosclerotic vascular disease in a parent, grandparent, or sibling with symptom onset or diagnosis before age 55 y for males and 65 y for females)
• * Current smoker
• * Left ventricular hypertrophy
• * Documented ankle brachial index of \<0.9
• * History of microalbuminuria, urine protein-creatinine ratio of \>2
• * CV disease (defined as one of the following):
• * Calcium score of \>0
• * ≥ 50 % occlusion of a coronary artery by angiography
• * ≥ 50 % occlusion of a carotid artery by angiography or ultrasound
• * History of stable angina
• * Symptomatic peripheral arterial disease
• * Prior MI, unstable angina, percutaneous coronary intervention, CABG, TIA, ischemic stroke, carotid endarterectomy, or other arterial surgery or angioplasty, which have occurred \> 3 months prior to screening visit
• * Diabetes Mellitus type 1 or 2 (considered a CV disease equivalent).
• * Clinical diagnosis of rheumatoid arthritis, as determined by individual patient and physician, requiring daily treatment with NSAIDs.
• 1. Unstable angina, MI, CVA, CABG \<3 months from screening visit
• 2. Planned coronary, cerebrovascular, or peripheral revascularization
• 3. Undergone major surgery within 3 months prior to screening visit or has planned major surgery during the study period
• 4. Uncontrolled hypertension (SBP \>190, DBP \>100 mm Hg) during screening visit
• 5. Uncontrolled arrhythmia \< 3 months from screening visit
• 6. NYHA class III-IV heart failure or if available, ejection fraction ≤ 35 %
• 7. Within 6 months prior to screening visit, a history of ACS or hospitalization for heart failure
• 8. Oral corticosteroid, prednisone (or equivalent) \> 20 mg daily
• 9. Anticoagulation therapy
• 10. Antiplatelet therapy except for aspirin
• 11. GI ulceration \< 60 days before screening visit
• 12. GI bleeding, perforation, obstruction \< 6 months of screening visit
• 13. Inflammatory bowel disease, diverticulitis active \< 6 months of screening visit
• 14. AST, ALT, or BUN \>2x the upper limit normal (within 30 days prior to screening visit)
• 15. Creatinine level \>1.7 mg/dL in men, 1.5 mg/dL in women (within 30 days prior to screening visit)
• 16. On fluconazole, methotrexate, or lithium therapy
• 17. Malignancy \< 5 years before screening visit
• 18. Other known, active, significant GI, hepatic, renal, or coagulation disorders
• 19. Allergy, allergic-type reactions or hypersensitivity (e.g. asthma, urticaria, etc.) to any of the study medications and its components (i.e. sulfonamides)
• 20. History of any disease of condition that, in the opinion of the investigator would place the subject at an unacceptable risk to participate in this study
• 21. Any clinically relevant abnormal findings in physical examination, vital signs, or previous laboratory works that, in the opinion of the investigator, may compromise the safety of the subject to participate
• 22. Subjects who are legally institutionalized
• 23. Lactating females or females of childbearing potential except for those who are surgically sterile or postmenopausal-