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.