COX-2 inhibitors and cardiovascular risk.

The development of drugs that selectively inhibit cyclooxygenase-2 (COX-2) demonstrates translational research from bench to bedside based on underlying knowledge of micro-cellular structure and function. However, theoretical concerns about potentially prothrombotic effects of selective COX-2 inhibitors coupled with observations of increased cardiovascular risk have produced significant consternation and lead to the withdrawal of two of these agents from the market. A number of questions remain unanswered. It appears clear that both selective and non-selective COX inhibitors are associated with increases in blood pressure. In addition, blood pressure is often increased after starting nonsteroidal therapy, and we know that even small increases in blood pressure in subjects with pre-existing vascular disease are associated with substantial increases in the risk of cardiovascular morbidity. Given this line of reasoning, one might hypothesize that the observed increases in the risk of cardiovascular events associated with COX-inhibitors are largely due to increases in blood pressure in populations of subjects who are already at high risk. But can we generalize that the adverse cardiovascular effects observed for rofecoxib and valdecoxib are sufficient to indict the entire class of COX-2 inhibitors, or is this not a class effect, but dependent upon the degree of COX-2 selectivity? In either case, it seems prudent to recommend that subjects who are at higher risk for a cardiovascular event and receiving a COX-inhibitor should also be treated with low dose ASA with close follow up of blood pressure and efficacious use of anti-hypertensive medications. Finally, modest dietary salt restriction may help lessen the effects of COX-inhibitors on blood pressure.