Relative Thromboembolic Risks Associated with COX-2 Inhibitors

OBJECTIVE To evaluate the clinical literature on cyclooxygenase-2 (COX-2) inhibitors to determine whether a greater incidence of thromboembolic events is universal within the drug class. DATA SOURCES A MEDLINE search was conducted (1996–March 2005) for key articles in the English language assessing the efficacy or safety of these agents. STUDY SELECTION AND DATA EXTRACTION Randomized, double-blind, and controlled trials, as well as case–control and retrospective cohort studies, that assessed the cardiovascular safety of COX-2 inhibitors were reviewed. DATA SYNTHESIS Seventeen published studies were reviewed, and the cardiovascular safety data were extracted from each trial. The mechanism by which COX-2 inhibitors may induce a thromboembolic event is likely multifactorial involving (1) COX-2–specific isoform binding affinity, (2) drug dose, (3) duration of therapy, and (4) cardiovascular risk profile of the patient. Evidence supports an association between cardiovascular adverse events and the use of rofecoxib, valdecoxib, and celecoxib. However, this risk is not equally distributed among the drugs. Given the relative paucity of data, lumiracoxib and etoricoxib cardiovascular effects remain uncertain. CONCLUSIONS Each COX-2 inhibitor has a unique cardiovascular risk profile. Based on the current evidence, celecoxib is the safest COX-2 inhibitor when prescribed appropriately in the lowest possible dose for the shortest duration in the ideal target population.