Risk of cardiovascular events associated with selective COX-2 inhibitors

Area of Science:

• Cardiovascular medicine
• Rheumatology
• Pharmacology

Background:

• Atherosclerosis involves inflammation; selective cyclooxygenase 2 (COX-2) inhibitors may offer antiatherogenic effects by reducing inflammation.
• However, COX-2 inhibitors can decrease prostacyclin production, potentially increasing prothrombotic activity.

Purpose of the Study:

• To assess the cardiovascular effects of COX-2 inhibitors in patients without coronary artery disease using arthritis and musculoskeletal pain medications.
• To evaluate the safety of COX-2 inhibitors concerning thrombotic cardiovascular events.

Main Methods:

• Conducted a MEDLINE search for English-language articles on COX-2 inhibitors (1998-February 2001).
• Reviewed pharmaceutical company submissions to the US Food and Drug Administration.
• Analyzed data from two major randomized trials (VIGOR, CLASS) and two smaller trials.

Main Results:

• The VIGOR trial showed a 2.38-fold increased risk of thrombotic cardiovascular events with rofecoxib compared to naproxen.
• The CLASS trial found no significant difference in cardiovascular events between celecoxib and nonsteroidal anti-inflammatory agents.
• Annualized myocardial infarction rates were significantly higher with both rofecoxib (0.74%) and celecoxib (0.80%) compared to placebo (0.52%) in primary prevention trials.

Conclusions:

• Available data suggest a potential increased risk of cardiovascular events associated with COX-2 inhibitors.
• Further prospective trials are needed to fully characterize and quantify this cardiovascular risk.