Research News

NSAIDs are linked to increased risk of venous thromboembolism, study finds

BMJ 2014; 349 doi: (Published 25 September 2014) Cite this as: BMJ 2014;349:g5834
  1. Jacqui Wise
  1. 1London

A meta-analysis has found a statistically significant increased risk of deep vein thrombosis and pulmonary embolism in users of non-steroidal anti-inflammatory drugs (NSAIDs), which has led researchers to say that these drugs should be prescribed with caution.

NSAIDs are among the most commonly used classes of drugs, but they are well known for their potential adverse effects. For example, in 2004 rofecoxib (Vioxx) was withdrawn from the market because of concerns about an increased risk of myocardial infarction and sudden cardiac death among users.

The new research,1 published online in the journal Rheumatology, included one cohort study and five case control studies with a total of 21 401 venous thromboembolism events. Randomised controlled trials were not included in the meta-analysis because venous thromboembolism is a relatively uncommon adverse effect that generally requires a larger sample size and a longer duration of follow-up.

The meta-analysis found a statistically significant increased risk of venous thromboembolism in users of NSAIDs compared with participants who did not use them (pooled risk ratio 1.80 (95% confidence interval 1.28 to 2.52)). Three studies reported a risk ratio among participants who used selective COX 2 inhibitors, and this was higher still (1.99 (1.44 to 2.75).

The study’s lead author, Patompong Ungprasert of the Bassett Medical Center in New York, said, “This is the first systematic review and meta-analysis of published observational studies assessing the risk of venous thromboembolism among NSAIDs users. Why NSAIDs may increase the risk of venous thromboembolism is unclear. It is possibly related to COX 2 inhibition leading to thromboxane-prostacyclin imbalance. Physicians should be aware of this association and NSAIDs should be prescribed with caution, especially in patients already at a higher risk of venous thromboembolism.”

The authors said that the six studies included in the meta-analysis were of high quality but had some limitations, so the results should be interpreted with caution. For example, all of the NSAIDs were evaluated as one group in the study, but not all individual drugs may increase the risk of venous thromboembolism. Also, as it was a meta-analysis of observational studies, it could not be certain that the NSAIDS themselves increased the risk of venous thromboembolism. For example, patients might have had NSAIDS prescribed for underlying illnesses that caused pain and immobility or for chronic inflammatory disorders that were linked to a higher venous thromboembolism risk than that of the general population.


Cite this as: BMJ 2014;349:g5834


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