Nussmeier NA et al. (2005) Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 352: 1081–1091

Patients receiving CYCLO-OXYGENASE 2 (COX2) INHIBITORS following coronary-artery bypass grafting (CABG) are at increased risk from serious adverse effects, such as myocardial infarction, cardiac arrest, stroke and pulmonary embolism, according to a recent double-blind, international study. Such concerns had been raised previously, but had not been proven statistically significant until now.

Patients who had undergone CABG with cardiopulmonary bypass were grouped according to risk strata and geographic location, and randomized to receive multiple doses of valdecoxib (Bextra®; Pfizer Ltd, Walton-on-the-Hill, UK) and its intravenous prodrug parecoxib (Dynastat®; Pfizer Ltd) (n = 550), placebo and oral valdecoxib (n = 560) or placebo alone (n = 600) over a 10-day postoperative period. Standard opioids were available to all patients.

During the 30-day follow-up period, the frequency of adverse cardiovascular, renal, gastrointestinal and surgical-wound-related complications was significantly higher for patients that received COX2 inhibitors (7.4%) compared with the group given placebo only (4.0%, P = 0.02). Separate analyses of event subtypes showed that this difference was primarily due to a significantly greater frequency of cardiovascular events in the parecoxib plus valdecoxib cohort.

The association between serious thromboembolic events and COX2 inhibition might be a function of the drugs interfering with production of the vasodilator PROSTACYCLIN. The investigators recommend that COX2 inhibitors should no longer be used in patients recovering from CABG, and suggest avoiding administration of drugs of this class to any person undergoing a vascular procedure for atherosclerotic disease.