Cardiac risks with COX-2 inhibitors

Linda Levesque and colleagues' findings concerning the timing of cardiovascular risks in elderly users of cyclooxygenase-2 (COX-2) inhibitors are interesting,1 but they might reflect the superiority of rofecoxib over other agents as an analgesic and anti-inflammatory agent rather than any specific cardiotoxic effect of this drug. The peak in the risk of cardiac events in the second week of treatment with rofecoxib might simply be related to increased activity levels in patients who had previously been in pain and who therefore had probably been less active and had experienced a decline in physical fitness. With a half-life of 24 hours, it takes 6 half-lives (about a week) for rofecoxib to reach steady state and maximal sustained efficacy. The finding that cardiac risk dropped back toward baseline after the second week could be explained by the patients' improved cardiac fitness resulting from a further week of increased physical activity. Perhaps we should be careful about how well we treat long-standing arthritis in those who long to be more active again.