Precaution, cyclooxygenase inhibition, and cardiovascular risk.

Cardiovascular risk led to the withdrawal of Vioxx (rofecoxib) in 2004. Some related drugs also increase cardiovascular risk and cyclooxygenase (COX)-2 inhibitors that remain on the market, including unselective non-steroidal anti-inflammatory drugs (NSAIDs), have not been exonerated. This article reviews if new evidence should change clinical and regulatory practice. Substantial COX-2 inhibition increases the incidence of cardiovascular disease unless concomitant platelet thromboxane production is inhibited by >95%. This can be investigated using whole blood assays, an approach used recently to show that acetaminophen (paracetamol) is a COX-2-selective inhibitor. The epidemiology available suggests acetaminophen, though readily available over-the-counter, does increase cardiovascular risk. Current evidence is inadequate to recommend many potential alternatives to Vioxx as safe. We argue that the precautionary principle, 'first do no harm', should underpin the regulation and prescribing of NSAIDs. Labelling which identifies these risks for prescribers and consumers should be mandatory.