Aspirin Resistance in Systemic Lupus Erythematosus (SLE)

This study examine whether patients with lupus respond to aspirin , and if not, if that is related to inflammation. We examine the ability of aspirin to inhibit the production of thromboxane in patients with lupus and controls and see if aspirin insensitive thromboxane production is inhibited by meloxicam.

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.

Arm: Aspirin and Meloxicam Each participant will receive 81 mg aspirin per day for 7 days, followed by meloxicam 7.5 mg daily plus aspirin 81 mg daily for 5 days

a hormone of the prostacyclin type released from blood platelets. It induces platelet aggregation and arterial constriction.

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

Kawai VK, Avalos I, Oeser A, Oates JA, Milne GL, Solus JF, Chung CP, Stein CM. Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus erythematosus: association with metabolic syndrome. Arthritis Care Res (Hoboken). 2014 Feb;66(2):285-92. doi: 10.1002/acr.22169.