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Cardiovascular safety of naproxen questioned

PLoS Clinical Trials has published the results of the Cardiovascular and Cerebrovascular Events in the Randomized, Controlled Alzheimer's Disease Anti-Inflammatory Prevention (ADAPT) Trial.

This study was stopped early in 2004 by the National Institute for Health. A press release stated "data from the ADAPT trial indicated an apparent increase in cardiovascular and cerebrovascular events among participants taking naproxen when compared to placebo".

The trial recruited patients aged 70 and over who had at least one first degree relative with Alzheimer's like dementia. NSAID use was excluded although antiplatelet doses of aspirin were permitted. Patients were then randomised to celecoxib, naproxen or matching placebos.

A composite endpoint including cardiovascular death, myocardial infarction, stroke, transient ischemic attack and heart failure was analysed and revealed a statistically significant increase in the number of events experienced in the naproxen arm of the study. At this point the study was terminated.

The study paper states "these results must be interpreted in the context of a trial that was stopped early, with small numbers of events that were not originally intended as specific outcomes".

An accompanying editorial is critical of the way the study was halted and states "the trial results cannot be reliably interpreted". As recently reported, the European Medicines Agency (EMEA) assessed the safety of all NSAIDS and concluded that a thrombotic risk could not be established for naproxen.

Action: The results of this study are not compelling enough to challenge the findings of the EMEA assessment. As previously recommended, naproxen is a suitable second line choice, after ibuprofen, where NSAIDs are indicated.