Tramadol linked to increased mortality risk in osteoarthritis patients
medwireNews: Mortality rates are significantly higher during the first year after a tramadol prescription than after prescription of common nonsteroidal anti-inflammatory drugs (NSAIDs), but it is unclear whether the relationship is causal, say researchers.
Indeed, they caution that the results “were susceptible to confounding by indication” because “participants with initial prescription of tramadol had a higher comorbidity burden than those with an initial prescription of NSAIDs before propensity score matching.”
The study included 44,451 patients aged 50 years and older with osteoarthritis who were prescribed tramadol between 2000 and 2015. These patients, who were all registered in a UK-wide general practice database (The Health Improvement Network), were matched using propensity scoring to patients with osteoarthritis who were prescribed naproxen (n=12,397), diclofenac (n=6512), celecoxib (n=5674), etoricoxib (n=2946), or codeine (n=16,922) during the same period.
Guanghua Lei (Central South University, Hunan, China) and colleagues found that, during the first year after their initial prescription, patients who received tramadol had a significant 1.70- to 2.04-fold increased risk for death from any cause relative to those who received naproxen, diclofenac, celecoxib, or etoricoxib, but were no more likely to die than patients who received codeine.
Mortality rates were 23.5 versus 13.8 per 1000 person–years for tramadol versus naproxen, 36.2 versus 19.2 per 1000 person–years for tramadol versus diclofenac, 31.2 versus 18.4 per 1000 person–years for tramadol versus celecoxib, and 25.7 versus 12.8 per 1000 person–years for tramadol versus etoricoxib.
The all-cause mortality rates in the cohort comparing tramadol with codeine were 32.2 and 34.6 per 1000 person–years, respectively.
Writing in JAMA, the researchers note that deaths due to cardiovascular and gastrointestinal causes, infection, cancer, and respiratory diseases were all higher with tramadol than with the four NSAIDs, but small numbers for each specific cause meant that most associations were not statistically significant.
During the course of the study the proportion of participants prescribed tramadol increased from 3.4% in 2000 to 11.1% in 2013, followed by a slight decrease to 9.8% in 2015.
Lei et al say that if their findings are “replicated and determined to likely be causal” they will have “clinical implications” that “indicate an unfavorable safety profile of tramadol.”
And despite current guidelines recommending the use of tramadol for knee osteoarthritis, “non-opioid therapy could be preferred for management of chronic pain (eg, osteoarthritis),” they add.
However, the authors also point out that the data “may not be generalizable to patients with other diseases whose disease pathophysiology may modify the effect of tramadol on mortality.”
By Laura Cowen
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