Sulfasalazine and Endothelial Function

Effect of Sulfasalazine on Endothelial Function

Experimental studies suggest that systemic inflammation leads to endothelial dysfunction and atherosclerosis. This study will examine the effects of the anti-inflammatory drug sulfasalazine on endothelial function in patients with coronary artery disease. Subjects will be treated with sulfasalazine or to placebo for six weeks. After a two-week rest period, subjects will cross over to the alternative treatment. Endothelium-dependent flow-mediated dilation of the brachial artery will be studied before and after each drug. We hypothesize that anti-inflammatory therapy will reverse endothelial dysfunction in patients with coronary artery disease.

Inclusion Criteria:

• History of coronary artery disease

Exclusion Criteria:

• G6PD deficiency defined by red blood cell G6PD activity assay
• Sulfa allergy
• Aspirin allergy
• Allergy to furosemide (lasix), hydrochlorthiazide, sulfonylureas, acetazolamide (Diamox) or other carbonic anhydrase inhibitors
• SGOT, SGPT, alkaline phosphatase, total bilirubin greater than 2 times the upper limit of normal
• WBC less than 4.0 or greater than 11.0 K/UL
• Platelet count less than 150 K or greater than 450K
• Hematocrit less than 30% 7
• Serum creatinine greater than 1.5 mg/dl
• Unstable angina or acute MI within 2 weeks
• Warfarin treatment
• Immunosuppressive treatment (methotrexate, cyclosporine, etc.)
• Digoxin treatment
• Phenytoin (Dilantin) treatment
• Methenamine (Mandelamine, Urex) treatment
• Probenecid or sulfinpyrazone (Anturane, Aprazone) treatment
• Porphyria
• Symptomatic GI obstruction
• GU obstruction (not including clinical evidence of benign prostatic hypertrophy)
• Pregnancy