Editorial: On the selective inhibitors of Cyclooxygenase-2: Do we have a last word?

Abstract

The cardiovascular safety of selective inhibitors of cyclooxygenase 2 (COX-2) has received a great deal of attention since the withdrawal of rofecoxib and valdecoxib and recently with the non-approvable decisions for etoricoxib and lumiracoxib by the Food and Drug Administration (FDA). Numerous reviews and editorials have attempted to bring clarity to a very complicated issue. Differences among the individual COX-2 inhibitors have been suggested, but it is difficult to compare risk because of the lack of head-to-head trials and different comparators used in the key studies. Attempts have been made to determine difference in agents through comparison of the current published trials and through metaanalysis. These comparisons are challenging because of differing patient populations, risk profile of the patients, and different comparators used in the various trials. However, an evaluation of the literature can provide some relevant information. For example, comparisons of agents with similar selectivity, such as etoricoxib and diclofenac, did not show a difference in thrombotic events or complicated gastrointestinal (GI) events in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) program [Canon et al. 2006]. A difference was noted, however, with heart failure and hypertension with etoricoxib and uncomplicated GI events with diclofenac. Also, when the population is at low risk for cardiovascular disease, as in the Celecoxib Long-term Arthritis Safety Study (CLASS), no differences are seen. The cardiac safety of COX-2 inhibitors is a Correspondence to: Carlos M. Ferrario, MD Hypertension and Vascular Research Center Wake Forest University School of Medicine Winston Salem, North Carolina 27157, USA Tel: 336-716-5819 Fax: 336-716-6644 cferrari@wfubmc.edu complex issue that needs further evaluation to determine the risk of these agents in individual patients. Understanding the mechanism behind the cardiovascular effects is also critical to assist in patient selection and evaluation of an individual’s risk versus benefit. While many have attempted to present the mechanism simplistically, two possible mechanisms, as reviewed below, have garnered the most attention to date.