Non-steroidal anti-inflammatory drugs (NSAIDs) may increase risk of vascular and gastrointestinal complications, according to a study published May 29 in The Lancet.

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The study was a meta-analysis of 639 randomized trials, and found that major vascular events were increased by about a third by a coxib (rate ratio [RR] 1.37, 95% CI 1.14–1.66; p=0.0009) or diclofenac (1.41, 1.12–1.78; p=0.0036), primarily due to an increase in major coronary events (coxibs 1.76, 1.31–2.37; p=0.0001; diclofenac 1.70, 1.19–2.41; p=0.0032). In addition, ibuprofen was found to significantly increased major coronary events (2.22, 1.10–4.48; p=0.0253), but not major vascular events (1.44, 0.89–2.33). Naproxen did not increase cardiovascular events.

Further, the study found that all NSAID regimens increased upper gastrointestinal complications (coxibs 1.81, 1.17–2.81, p=0.0070; diclofenac 1.89, 1.16–3.09, p=0.0106; ibuprofen 3.97, 2.22–7.10, p<0.0001; and naproxen 4.22, 2.71–6.56, p<0.0001).

The authors note that their analysis "showed clearly that the vascular risks of diclofenac, and possibly ibuprofen, are similar to coxibs, but that naproxen is not associated with an increased risk of major vascular events." They add that their study "indicates that the effects of different regiments in particular patients can be predicted, which could help in guiding decisions about the clinical management of inflammatory disorders."

In a related editorial comment, Marie R. Griffin of the Department of Preventative Medicine at Vanderbilt University Medical Center in Nashville, TN, notes that the study "leaves large gaps about risks associated with lower NSAID doses, longer durations of use, and residual effects after stopping treatment." She adds that, "identification of safe and effective strategies for chronic pain is sorely needed. In the meantime, long-term use of high-dose NSAIDs should be reserved for those who receive considerable symptomatic benefit from the treatment and understand the risks."

Keywords: Risk, Cyclooxygenase 2 Inhibitors, Pain, Gastrointestinal Diseases, Chronic Pain

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