Tramadol has been associated with an increased risk of all-cause mortality and hip fractures one year after the first prescription
With opioid use reportedly rising among rheumatoid patients in Europe, a study of osteoarthritis (OA) patients in British Columbia, Canada, adds to the growing evidence of the risk of hip fractures and all-cause mortality associated with tramadol.
Pain relief is a primary concern for OA patients, since no effective treatments are available to halt OA progression.
Tramadol is a so-called weak opioid, introduced in Australia in late 1998 – but no longer recommended by Australian peak medical bodies after reports of adverse effects increased steadily year on year and a 2019 Cochrane review underscored that position.
According to estimates published in late 2016, around 5% of OA patients in Australia are on tramadol, with a similar proportion of users among OA patients in British Columbia, Canada, as of 2014.
However, tramadol is associated with a higher rate of mortality and risk of hip fractures than other pain relief medications commonly prescribed for OA, such as nonsteroidal anti-inflammatory drugs (NSAIDs).
And yet since 2012, the American College of Rheumatologists has conditionally recommended tramadol as first-line therapy for patients with knee OA, along with NSAIDs.
Researchers from the Arthritis Research Canada have now examined the risk of cardiovascular disease (CVD) and venous thromboembolism (VTE), as well as all-cause mortality and hip fractures, associated with tramadol prescription among OA patients in British Columbia, Canada, between 2005 to 2014.
Lead author and PhD candidate Lingyi Li, from the University of British Columbia, presented their findings at the 2020 EULAR conference.
The study – which compared tramadol with three NSAIDs (naproxen, diclofenac and Cox-2 inhibitors) and codeine in over 112,000 Canadian OA patients – reaffirms previous findings from UK cohorts published earlier this year.[1],[2]
Tramadol was associated with an increased risk of all-cause mortality and hip fractures one year after the first prescription, compared with all three NSAIDs, but not codeine.
A higher one-year risk of CVD and VTE among tramadol users was also reported compared with patients prescribed diclofenac and Cox-2 inhibitors only.
Professor David Hunter, a rheumatologist from the Institute of Bone and Joint Research in Sydney, said the inclusion of CVD and VTE in this analysis is novel and may provide some mechanistic insights into the cause of the increased mortality associated with tramadol – although there is always potential for confounding effects with observational studies.
Professor Hunter noted that the reported increase in absolute risk for all-cause mortality, VTE and CVD was only small, however, he said the result was important considering how frequently this medication was used worldwide.
“Even a small [increase in] absolute risk leads to a relatively large number of [adverse] cases, as were seen in this relatively large sample size,” he said.
Professor Hunter also stressed that the risk for VTE, hip fractures and concomitant cardiovascular disease is already higher in people with OA – before adding tramadol into the mix.
“With the real risks of morbidity and mortality in an at-risk population [of OA patients], there is little justification for its use,” he said.
Association of tramadol with all-cause mortality, cardiovascular disease, venous thromboembolism and hip fractures among patients with osteoarthritis: A population-based study, Ann Rheum Dis 2020, 2 June
[1] https://jamanetwork.com/journals/jama/fullarticle/2727448
[2] https://asbmr.onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3935
