Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Traditional non-steroidal anti-inflammatory drugs (tNSAIDs, such as ibuprofen)) and newer selective cyclooxygenase-2 inhibitors (coxibs) are widely used for analgesia, but they have potentially serious vascular and gastrointestinal risks. The sponsors of coxib trials and their investigators provided data to form a collaboration (the Coxib and traditional NSAID Trialists’ [CNT] Collaboration) in order to assemble a database of individual participant data from all unconfounded trials, published and unpublished, of at least four weeks duration which have involved a coxib or tNSAID. The chief aim of this Collaboration was to conduct analyses of the effects of coxibs and tNSAIDs on the most common adverse effects of coxibs and tNSAIDs, namely “major vascular events” (heart attack, stroke or dying from cardiovascular disease)” and “symptomatic ulcer or upper gastrointestinal (GI) complications” as described in the protocol.

The resulting analyses, published in the Lancet in 2013, showed that high doses of diclofenac and ibuprofen increased the risk of a major vascular event by around one third. Most of this additional risk was due to an increased risk of heart attacks. In contrast, high doses of naproxen did not appear to increase the risk of heart attacks, probably because naproxen also has protective effects that balance out any extra risk of heart attacks.

The research also showed that the risks of ulcer bleeding were increased by between 2- and 4-fold, depending on the NSAID regimen, but the consequences of such bleeding were not usually serious. Details of the trials that contributed to these analyses can be found in the Supplementary Tables.

MRC press release 30 May 13


Our team

Selected publications

Related research themes