Aspirin Resistance in Systemic Lupus Erythematosus (SLE)

Premature cardiovascular disease is a major cause of mortality in patients with systemic lupus erythematosus (SLE) with the risk of myocardial infarction increased up to 50-fold. In addition to defining the mechanisms for accelerated atherosclerosis it is important to define the effects of drugs used to reduce cardiovascular risk in high-risk patients. Low dose aspirin, by inhibiting thromboxane A2 biosynthesis, has profound antiplatelet effects, but some patients have impaired thromboxane suppression - a phenomenon termed aspirin resistance. An explanation is that aspirin-independent thromboxane synthesis may occur through enhanced COX-2 activity, as would occur in an inflammatory condition such as lupus. However, little is known about the effects of low-dose aspirin in SLE. Thus, we propose to test the following hypothesis: 1) that aspirin insensitive thromboxane biosynthesis is increased in patients with lupus and is mediated by increased COX-2 activity.

Inclusion criteria

• Written Informed consent.
• Age >18 yrs.
• SLE meeting ACR criteria {Tan, Cohen, et al. 1982 1482 /id} for at least 6 months.(SLE group)
• Stable disease activity as evidenced by no change in immunosuppressive therapy in the past 1 month.
• If female of childbearing potential must use an effective method of birth control

Exclusion criteria

.

• Renal disease (creatinine >1.5 mg/dL, dialysis, 2+ or more proteinuria)
• Previous or current history of peptic ulcer disease or gastrointestinal bleed.
• Previous or current thromboembolic or ischemic cardiovascular event (stroke, myocardial infarction, angina) - can do aspirin part of study.
• Currently taking an anticoagulant or antiplatelet agent (besides aspirin).
• Thrombocytopenia (platelet count <135,000)
• Pregnancy
• Allergy to aspirin, NSAIDs
• NSAIDs in the previous week