Use of NSAIDs--An Update

The articles for this week deal with the positive and negative actions of NSAIDs. This particular article primarily addressed a popular news topic: the increase in risk for cardiovascular and cerebrovascular events due to selective COX-2 inhibitors. These drugs looked promising for pain relief without the unwanted side affect of GI bleeding that occurs with COX-1 inhibition. However, in September 2004, Merck withdrew its product, Vioxx, from the market and the concerns for COX-2 inhibitors increased significantly.

The American Heart Association released this article as an update on the safety of using NSAIDs. An FDA joint meeting came to the conclusion that celecoxib (Celebrex), valdecoxib (Bextra) and rofecoxib (Vioxx), all selective COX-2 inhibitors, “significantly increase the risk of cardiovascular events in a dose-dependent manner.” Although celecoxib is still on the U.S. market, it comes with a strict “black box” warning.

The article by Antman et al. stated the hypothesis that the increased risk for CV events is due to a shift in the prothrombotic/antithrombotic balance on endothelial cells. The shift leans toward thrombosis. It is believed this occurs because platelet aggregation is COX-1-dependent and so this mechanism would still work. In addition, COX enzymes catalyze the production of prostacyclin in endothelial cells which can disrupt platelet aggregation. So selective COX-2 inhibition would keep COX-1 activated while decreasing prostacyclin production and thus decreasing antithrombotic activity. The hypothesis also includes the fact that COX-2 inhibition increases sodium and thus water reabsorption (which can cause edema) and can increase risk for heart failure and hypertension (since activation of COX ultimately causes “local smooth muscle cell relaxation and vasodilation” and this would be inhibited).

The article concludes basically by saying that patients who must have NSAID treatment should first try acetaminophen or aspirin, the least risky NSAIDs. If this doesn’t work, then they should be prescribed nonselective NSAIDs. Selective COX-2 inhibitors should only be prescribed if absolutely necessary, and in the lowest dose and for the shortest duration possible. Any patients with a medical history of CV problems should seriously weigh the risks and benefits.