Patients receiving tramadol for osteoarthritis more likely to die, fracture hip
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Patients who receive tramadol for osteoarthritis demonstrate an increased risk for hip fractures, venous thromboembolism and mortality, compared with those treated with NSAIDs, according to data published in Arthritis Research and Therapy.
“As suggested by a recent meta-analysis on the comparative effectiveness of NSAIDs and opioid use for knee OA, there is no statistically significant difference in pain relief between tramadol and NSAIDs among OA patients; however, tramadol is associated with more opioid-related adverse effects, for example, nausea, dizziness, constipation, tiredness, headache, vomiting, and drowsiness,” Lingyi Li, MSc, of Arthritis Research Canada, and colleagues wrote.
“Several studies have compared risks of serious adverse events between tramadol and alternative commonly prescribed analgesics in patients with OA using the Health Improvement Network data that includes 6% of the U.K. population,” they added. “These studies showed that tramadol was associated with a significantly higher risk of mortality, myocardial infarction (MI), and hip fractures as compared to commonly prescribed NSAIDs. However, to describe the safety profile of tramadol among OA patients, the results need to be confirmed in a truly population-based sample.”
To analyze the safety profile of tramadol, compared with NSAIDs, among patients with OA, Li and colleagues reviewed information on from the Population Data British Columbia database. Patients were considered eligible for inclusions if they were aged older than 50 years, diagnosed with OA and received medical care between Jan. 1, 2005, and Dec. 31, 2013. For their study, the researchers defined OA based on when a patient visited health care professionals for the disease on at least two occasions within 2 years. A single discharge from a hospital with an OA code was also sufficient.
Researchers conducted a sequential, propensity score-matched cohort study with a total of four cohorts. In addition to the tramadol cohort, patients who received initial prescriptions for naproxen, diclofenac, a cyclooxygenase-2 inhibitor, or codeine were also evaluated. Patients were followed for at least 1 year. Assessed outcomes included all-cause mortality, incident cardiovascular diseases consisting of myocardial infarction or ischemic stroke, VTE consisting of pulmonary embolism or deep vein thrombosis, and hip fractures within the first year of treatment initiation.
A total of 100,358 patients with OA included in the analysis. Among these patients, 12,269 were in the naproxen cohort, 15,749 in the diclofenac cohort, 15,421 in the cyclooxygenase-2 inhibitor cohort and 6,751 in the codeine cohort.
According to the researchers, there was no difference CVD risk between the tramadol and other cohorts. However, for all-cause mortality, tramadol demonstrated a higher rate than naproxen (rate difference per 1,000 person-years [RD] = 3.3; 95% CI, 0-6.7), diclofenac (RD = 5.6; 95% CI, 2.3-9) and cyclooxygenase-2 inhibitor (RD = 8.1; 95% CI, 4.9-11.4). The rate was not higher in the codeine group (RD = –3.8; 95% CI, –9.2 to 1.5). Tramadol also had an association with VTE when compared with diclofenac (RD = 2.2; 95% CI, 0.7-3.7), and with hip fractures, compared with diclofenac (RD = 1.9; 95% CI, 0.4-3.4) and cyclooxygenase-2 inhibitors (RD = 1.7; 95% CI, 0.2-3.3).
“Although further evidence on the relationship between tramadol and mortality and morbidity outcomes is required, the accumulation of evidence of the risks associated with its use suggests that current guidelines on tramadol use in clinical practice might need to be revisited,” Li and colleagues wrote. “We found that the initiation of tramadol was associated with a higher risk of mortality (20% to 50%), VTE (70%), and hip fractures (40% to 60%) over 1 year of follow-up compared with commonly prescribed NSAIDs, but not with codeine.”
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David A. McLain, MD, MACR, FACP, FRCP
This is a big data study comparing new starts of tramadol to new starts of naproxen, diclofenac, Cox-2 NSAIDs or codeine in the treatment of osteoarthritis. The authors point out the worldwide burden of OA, with more than 300 million affected, and as the second costliest health condition in the United States. They also point out that there is no effective way, to date, to prevent progression. Tramadol patients were older, had a longer duration of OA, had more health care visits and hospitalizations, had more comorbidities, and a higher use of other prescriptions than the other groups.
The authors used propensity matching to overcome these differences. The variable that they didn’t have access to was OA disease severity. It appears from the baseline data that the tramadol group was sicker. They did show worse outcomes with tramadol. They suggest that the increase of usage in the United States, United Kingdom and Canada, I presume due to the opioid crisis, has a cost as well.
In rheumatology practice, we find that the NSAIDs we write are being stopped by nephrology, cardiology and gastroenterology, or even by us due to adverse effects. It leaves the OA patient with few options. Sometimes the best we can do is to try low doses of several medications and hope that this helps.
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