The Association of Celecoxib, Rofecoxib, and Non-selective Nonsteroidal Anti-inflammatory Medications with Indices of Thrombosis and Endothelial Function in the Multi-ethnic Study

Background: Cyclooxygeanse-2 (COX-2) inhibitors and non-selective nonsteroidal anti-inflammatory medications (NSAIDs) have been associated with increased cardiovascular risk. COX-2 inhibition may lead to an imbalance in prostanoids producing a prothrombotic state, thereby increasing cardiovascular events. Limited data exists on indices of thrombosis in patients taking these medications. Methods: Through a cross-sectional analysis of subjects within the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated the association between use of celecoxib (n=235), rofecoxib (n=163), and non-selective NSAIDs (n=1121) use with d-dimer, fibrinogen, von Willebrand Factor (vWF), Factor VIII, ICAM-1, PAI-1 compared with controls (n=5180). Results: There was a statistically significant association of elevated d-dimer levels with use of celecoxib (p<0.0001), rofecoxib (p=0.0014) and non-selective NSAIDs (p=0.0003). Also, subjects taking celecoxib at high doses (>250mg daily) had significantly higher ddimer levels than those taking lower doses (<150mg daily). These associations continued to be present after logarithmic transformation of d-dimer. There was an effect modification of aspirin use upon the relationship of COX-2 inhibitor and non-selective NSAID use and d-dimer that was not present after logarithmic transformation of d-dimer. Conclusions: The current analysis supports the hypothesis that the cardiovascular risk associated with COX-2 inhibitors and non-selective NSAID results from increased thrombotic proclivity.