Canada: Osteoarthritis (OA) patients treated with tramadol are at increased risk of venous thromboembolism, hip fractures, and mortality compared with treatment with NSAIDs, but not with codeine, says a new study. The study results were published in Arthritis Research and Therapy.
Tramadol use among OA patients has been increasing rapidly across the globe, but there is scarcity of population-based studies on its safety profile among OA patients. Considering this, J. Antonio Aviña-Zubieta, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and colleagues sought to determine if the use of tramadol in OA patients is associated with increased risks of cardiovascular diseases (CVD), venous thromboembolism (VTE), hip fractures, and all-cause mortality compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine.

For this purpose, the researchers conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013 using administrative health datasets from British Columbia, Canada. Matching of the tramadol cohort (i.e., tramadol initiation) was done with four comparator cohorts (i.e., initiation of naproxen, cyclooxygenase-2 [Cox-2] inhibitors, diclofenac, or codeine).
Outcomes are hip fractures, CVD, VTE, and all-cause mortality within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Hazard ratios were estimated using Cox proportional hazard models after adjusting for competing death risk.
A total of 100,358 OA patients were included (mean age: 68 years, 63% females).
Based on the study, the following findings were revealed:
All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 to 8.1 and hazard ratios (HRs) ranging from 1.2 to 1.5.
For CVD, no differences were observed between tramadol and NSAIDs.
Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years of 2.2 and HR of 1.7.
Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years of 1.9 and 1.7, respectively, and HRs of 1.6 and 1.4 respectively.
No differences were observed between tramadol and NSAIDs for all events.
"In this population-based cohort study, we found that the tramadol initiation was associated with a higher risk of VTE (70%), mortality (20–50%), and hip fractures (40–60%) over 1 year of follow-up versus commonly prescribed NSAIDs, but not with codeine," the authors concluded.
Reference:
Li, L., Marozoff, S., Lu, N. et al. Association of tramadol with all-cause mortality, cardiovascular diseases, venous thromboembolism, and hip fractures among patients with osteoarthritis: a population-based study. Arthritis Res Ther 24, 85 (2022). https://doi.org/10.1186/s13075-022-02764-3