OP0191 ASSOCIATION OF TRAMADOL WITH ALL-CAUSE MORTALITY, CARDIOVASCULAR DISEASE, VENOUS THROMBOEMBOLISM AND HIP FRACTURES AMONG PATIENTS WITH OSTEOARTHRITIS. A POPULATION-BASED STUDY
Authors: L. LI, N. Lu, H. Xie, J. Cibere, J. Kopec, J. Esdaile, J. A. Aviña-Zubieta
Journal: Annals of the Rheumatic Diseases (2020)

Background: Both tramadol (narcotic-like drug) and nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for pain relief among osteoarthritis (OA) patients. Evidence comparing risks of adverse events between tramadol and NSAIDs users is inconclusive. Objectives: To examine the association of tramadol with all-cause mortality, cardiovascular disease (CVD), venous thromboembolism (VTE) and hip fractures (HFx) compared with NSAIDs and codeine in OA. Methods: Design: Sequential propensity score-matched cohort study. Sample: All patients with OA who received medical care from 2005 to 2014 in the entire province of British Columbia, Canada. Tramadol cohort: Initial prescription of tramadol (n=56325). Four comparator cohorts: the initiation of one of the following: naproxen (n=13798), diclofenac (n=17675), cyclooxygenase-2 [Cox-2] inhibitor (n= 17039), or codeine (a weak opioid) (n=7813). Patients required to be prescribed neither tramadol nor its comparators during the year before the initial prescription date (i.e., index date). Outcomes: 1) all-cause mortality; first ever 2) CVD, 3) VTE, 4) HFx within the 1 st year after the initiation of tramadol or its comparators. Follow-up: from index date until the event occurred, disenrollment, or the end of a 1-year follow-up period. Statistical analysis: We created baseline covariates (demographics, comorbidities, medications and health resource utilization) from the year prior to the index date. Calendar years from 2005 to 2014 were divided into 10 blocks; propensity scores were calculated using logistic regression within each block. We used 1:1 greedy matching method. We estimated hazard ratios (HRs) using Cox proportional hazard models. Results: After propensity score matching, 112650 patients with OA were included (mean age of 68 years, 62.8% were females). During the 1-year follow-up, 296 deaths (21.5/1000 person-years) occurred in the tramadol cohort and 246 (17.8/1000 person-years) in the naproxen cohort (Table 1). All-cause mortality was higher for tramadol compared with all NSAIDs cohorts, but not with the codeine cohort (Table 1, Figure 1). Tramadol initiators have also a higher risk of CVD and VTE compared with the diclofenac and Cox-2 inhibitor initiators with HRs ranging from 1.2 to 1.7. Furthermore, tramadol was also associated with a higher risk of HFx compared with all NSAIDs cohorts (HRs ranging from 1.4 to 1.5). No significant difference was found between tramadol and codeine (Table 1). Table 1 Group1 Group2 Group3 Group4 All-cause Mortality Tramadol Naproxen Tramadol Diclofenac Tramadol Cox-2 inhibitor Tramadol Codeine OA (n) 13798 13798 17675 17675 17039 17039 7813 7813 Death (n) 296 246 439 345 402 267 168 199 Rate (/1000 PY) 21.5 17.8 24.8 19.5 23.6 15.7 21.5 25.5 HR (95% CI) 1.2 (1.0-1.4) 1.0 1.3 (1.1-1.5) 1.0 1.5 (1.3-1.8) 1.0 0.8 (0.7-1.0) 1.0 CVD OA (n) 11708 11708 14924 14924 14779 14779 6809 6809 CVD (n) 309 319 410 349 404 353 156 164 Rate (/1000 PY) 26.4 27.3 27.5 23.4 27.3 23.9 22.9 24.1 HR (95% CI) 1.0 (0.9-1.1) 1.0 1.2 (1.1-1.3) 1.0 1.2 (1.0-1.3) 1.0 0.9 (0.8-1.1) 1.0 VTE OA (n) 13472 13472 17230 17230 16699 16699 7660 7660 VTE (n) 41 37 60 40 70 40 28 30 Rate (/1000 PY) 3.0 2.8 3.5 2.3 4.2 2.4 3.7 3.9 HR (95% CI) 1.2 (0.9-1.6) 1.0 1.5 (1.1-1.9) 1.0 1.7 (1.3-2.3) 1.0 1.0 (0.7-1.4) 1.0 HFx OA (n) 13378 13378 17216 17216 16670 16670 7593 7593 HFx (n) 66 49 88 59 91 60 35 40 Rate (/1000 PY) 5.0 3.7 5.1 3.4 5.5 3.6 4.6 5.3 HR (95% CI) 1.4 (1.0-1.8) 1.0 1.5 (1.2-1.9) 1.0 1.5 (1.2-1.9) 1.0 0.9 (0.7-1.2) 1.0 Conclusion: OA patients initiating tramadol have an increased risk of mortality, CVD, VTE, and HFx within 1 year compared with NSAIDs, but no statistically significant difference in the risk was observed between tramadol and codeine. Disclosure of Interests: None declared