Journal Article

Association of tramadol with all-cause mortality, cardiovascular diseases, venous thromboembolism, and hip fractures among patients with osteoarthritis: a population-based study

Li, Lingyi, Cibere, Jolanda, Kopec, Jacek A., Aviña-Zubieta, J. Antonio, Lu, Na, Marozoff, Shelby, Esdaile, John M., Xie, Hui

2022

Overview

Background The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine. Methods Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures 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. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death. Results Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0–6.7) to 8.1 (4.9–11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0–1.4) to 1.5 (1.3–1.8). 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 (95% CI) of 2.2 (0.7–3.7) and HR (95% CI) of 1.7 (1.3–2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4–3.4) and 1.7 (0.2–3.3), respectively, and HRs (95% CI) of 1.6 (1.2–2.0) and 1.4 (1.1–1.9), respectively. No differences were observed between tramadol and NSAIDs for all events. Conclusions OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Anti-Inflammatory Agents, Non-Steroidal - adverse effects / Arthritis / Cardiovascular disease / Cardiovascular diseases / Cardiovascular Diseases - chemically induced / Care and treatment / Codeine - adverse effects / Cohort Studies / Complications and side effects / Cyclooxygenase 2 Inhibitors - adverse effects / Development and progression / Diclofenac - therapeutic use / Dosage and administration / Epidemiology / Female / Fractures / Health risks / Hip fractures / Hip Fractures - chemically induced / Hip Fractures - drug therapy / Hip Fractures - epidemiology / Hip joint / Humans / Male / Medicine / Medicine & Public Health / Mortality / Nonsteroidal anti-inflammatory drugs / Orthopedics / Osteoarthritis / Osteoarthritis - chemically induced / Osteoarthritis - drug therapy / Population-based studies / Prevention / Rheumatology / Risk factors / Thromboembolism / Tramadol / Tramadol - adverse effects / Venous thromboembolism / Venous Thromboembolism - chemically induced / Venous Thromboembolism - drug therapy / Venous Thromboembolism - epidemiology