NSAIDs and cardiovascular adverse events: Is increasing risk associated with increasing Cox-II selectivity ratios?

Abstract

Background. Recent studies have suggested there is an increased risk of cardiovascular (CV) events with some or all of the more Cox-II selective NSAIDs. One theory for this increased risk proposes that a shift in the balance between prostacyclin, an antithrombotic vasodilator that is reduced by Cox-II inhibition, and thromboxane A2, a prothrombotic vasoconstrictor that is reduced by Cox-I inhibition will theoretically increase the risk for CV and thrombotic events. This study attempts to specifically evaluate this theory by examining the association between CV events and the relative Cox-II to Cox-I selectivity of NSAIDs. Methods. Using 2000-2001 MarketScan claims data, cross-sectional and longitudinal analyses were performed. Univariate and bivariate analyses were performed to describe and compare new, adult users of NSAIDs. Propensity score matching was used to create a subset of these users, which was balanced across numerous covariates. Finally, multivariate, time to event analyses were performed using the matched sample to test the association between relative Cox-II to Cox-I selectivity ratio and possible adverse cardiovascular events. Results. Patients who were older, male, and had higher baseline cardiovascular risk were significantly more likely to receive a higher Cox-II selective drug than a lower Cox-II selective drug. In the propensity score matched sample, adjusted for confounders, the hazard of CV event was not significantly associated with increasing Cox-II selectivity ratios. Conclusion. This study shows that patients with an increased baseline risk of CV events are significantly more likely to receive a higher Cox-II selective NSAID. After controlling for these baseline differences, no significant association was found between selectivity ratios and CV events. Therefore, using Cox-II selectivity ratios to rank order NSAIDs in terms of risk of CV events is not appropriate and practitioners should not rely on selectivity ratios in making prescribing decisions. Additional studies should evaluate other potential mechanisms contributing to the CV risk of NSAIDs, while further study, in a larger sample and for a longer duration, should be performed to confirm the absence of an association between CV adverse events and Cox-II selectivity ratios.