Are Coxibs better than NSAIDs for the Treatment of Chronic Pain?

A study published in the August issue of BMC Musculoskeletal Disorders has addressed the controversial topic of non-steroidal anti-inflammatory drugs (NSAIDs) versus cyclooxygenase-2 selective inhibitors (coxibs) analgesics in the treatment of chronic pain. In particular the authors explored the incidence of serious gastrointestinal and cardiovascular adverse events between the two groups of drugs. It is recognised that these outcomes are dependent on the chosen drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. Overall results of this study were generally in favour of the coxibs.

Chronic pain is defined as pain of at least moderate severity that occurs on most days for a period of at least 6 months. Chronic pain is a common complaint affecting approximately 20% of the general population. It may be associated with a wide range of diseases and can markedly impair the quality of life of its sufferers. Chronic musculoskeletal pain can be challenging to treat and frequently requires prescription of anti-inflammatory medications. Traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 selective inhibitors (coxibs) are both viable treatment options for chronic pain associated with osteoarthritis. Unfortunately these agents have potential life-threatening side effects including gastrointestinal harm, acute renal failure, congestive heart failure and cardiovascular harm. Adverse effects of NSAIDs and coxibs have been largely publicised in recent years and much confusion exists regarding the role of cox-2 selective inhibitors in the management of chronic pain. Researchers from the Pain Research and Nuffield Department of Anaesthetics and the University of Oxford have recently published an article specifically evaluating the gastrointestinal and cardiovascular risks of cox-2 selective inhibitors versus NSAIDs. The authors pooled data from valid meta-analyses of clinical trials and cohort studies to clearly define the incidence of these side effects. Relevant trials predominantly included patients with chronic pain from osteoarthritis, rheumatoid arthritis, back pain or ankylosing spondylitis. Gastrointestinal side effects included complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers, and serious cardiovascular outcomes where defined as ATPC (antiplatelet trial collaborators) events which included myocardial infarctions, strokes or vascular deaths. Five different coxibs were specifically analysed, namely celecoxib, etoricoxib, valdecoxib, rofecoxib and lumiracoxib. Annualised rates of individual adverse events were calculated and compared to those of traditional NSAID treatments. Researchers hoped their clarifications of relationships and comparisons between the drugs would simplify treatment choices.As expected the primary results of the study showed that patients treated with a coxib rather than NSAID had overall fewer complicated upper gastrointestinal events. In addition per 1000 patients treated for a year there would be one more fatal or nonfatal heart attack or stroke in the coxib group. However, overall rates of major cardiovascular events were considered similar between NSAIDs and coxibs. More specifically, three of the included drugs had sufficient data and numbers of events to allow direct individual comparisons. It was found that for every 1000 patients treated with one year duration of therapy with celecoxib (instead of an NSAID) 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes would occur. For rofecoxib there would be six fewer upper gastrointestinal complications, but three more fatal or nonfatal heart attacks or strokes. Finally for lumiracoxib it was noted that eight fewer upper gastrointestinal complications, but one more fatal or nonfatal heart attack or stroke would occur. In the individual analysis results were in favour of each of the coxibs in terms of gastrointestinal bleed risk. Researchers concluded that the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events for each coxib treatment. Surprisingly rates of cardiovascular events were also in favour of celecoxib and valdecoxib versus NSAID, perhaps contrary to previous beliefs regarding the cardiovascular risks of coxib agents. The latter two agents may therefore be the safest analgesic options to avoid serious adverse events. However, this study only included two rare harmful events and other side effects such as congestive heart failure, renal impairment and anaemia may warrant further consideration. Moreover, heart attack and stroke may be potentially more fatal outcomes than gastrointestinal bleeding so the small increase in the number of cardiovascular events with the other coxibs may be deemed relevant. In conclusion this study shows that coxib analgesics may produce less serious gastrointestinal outcomes without a significant increase in the rates of serious cardiovascular events. This suggests coxib treatments may be the favoured analgesic options for chronic pain sufferers despite recent poor media reputations. Medical practitioners however should be wary of the wide range of available therapies and tailor treatment to their individual patients’ co-morbidities and response. Source:

1. Moore R, Derry S, McQuay H. Cyclo-oxygenase-2 selective inhibitors and nonsteroidalanti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk, BMC Musculoskeletal Disorders 2007; 8 (73): 1-11.