Both tramadol and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain relief in osteoarthritis patients. However, the evidence comparing the risks of adverse events between tramadol and NSAIDs users has been inconclusive. Thus, Lingyi Li (University of British Columbia, Canada) and colleagues assessed the association of tramadol with all-cause mortality, CVD, VTE, and hip fractures compared with NSAIDs and codeine in osteoarthritis patients.
This was done in a sequential propensity score-matched cohort study. Eligible participants were osteoarthritis patients who received medical care from 2005 to 2014 in the province of British Columbia, Canada. The tramadol cohort included 56,325 patients who had an initial prescription of tramadol. The 4 comparator cohorts included patients who had initiated one of the following: naproxen (n=13,798), diclofenac (n=17,675), cyclooxygenase-2 [Cox-2] inhibitor (n=17,039), or codeine (n=7,813). Participants required to be prescribed neither tramadol nor its comparators during the year prior to the initial prescription date. Outcomes were all-cause mortality; first ever CVD, VTE, and hip fracture within 1 year after the initiation of tramadol or its comparators. Patients were followed-up from index date until the event occurred, disenrollment, or the end of a 1-year follow-up period. After propensity score matching, a total of 112,650 patients with osteoarthritis were included (mean age of 68 years; 62.8% was female).
During the 1-year follow-up, 296 deaths (21.5/1,000 person-years) occurred in the tramadol cohort and 246 (17.8/1,000 person-years) in the naproxen cohort. Patients with osteoarthritis who were treated with tramadol had a 20-50% higher risk of death during the first year of treatment than patients who were treated with NSAIDs, but no significant difference was observed compared with the codeine cohort. Compared with the NSAIDs cohort, patients treated with tramadol also had an increased risk of CVD, VTE, and hip fracture (see Figure). The impact of pain severity as a factor necessitating tramadol prescription and potential confounders associated with this including reduced mobility as potentially relevant mechanisms merits further considerations.
Figure: Outcomes on mortality. Adapted from [1]

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