According to the CDC, it is estimated that about 20% of the U.S. population suffers from chronic pain. Compared with other demographic groups, chronic pain is highest among women, occurring in about 21.7%. Given that the lifetime risk of developing BC in the U.S. is about 13%, the potential exists for women suffering from chronic pain to also develop BC. Data are conflicting about the risks of increased mortality associated with the use of tramadol for chronic pain.
Researchers conducted a head-to-head, propensity score-matching study to help clarify the impact of tramadol on overall survival (OS) among women who used the opioid for noncancer pain prior to receiving a BC diagnosis.
Using data from the Taiwan Cancer Registry database, patients were identified as those who had a diagnosis of chronic pain prior to receiving a diagnosis of BC between January 1, 2008, and December 31, 2017. To be included in the study, patients aged 20 years or older had to be on an analgesic and have a diagnosis of chronic pain as determined by the presence of an ICD-9 code for osteoarthritis, spinal disorders, peripheral vascular disease, osteoporosis, gout, headache, diabetic neuropathy, rheumatoid arthritis, pressure ulcer, or herpes zoster.
Long-term tramadol use—which was defined as the use of tramadol on most days for more than 3 months with a mean tramadol dose of >180 defined daily doses per year—had to have occurred prior to a BC diagnosis. The case group consisted of those who received the above amount of tramadol prior to the index data of a BC diagnosis and the control group, which was comprised of those who were not prescribed tramadol prior to the index data of a BC diagnosis. This control group could have received nonsteroidal anti-inflammatory agents or other opioids. Patients who used long-term tramadol following the diagnosis of BC were not included in the study.
Patients were matched based on propensity scores for sex, age, comorbidities, income level, urbanization, menopausal status, human epidermal growth factor receptor-2 status, nodal surgical types (sentinel versus axillary), American Joint Committee on Cancer clinical stage, hormone receptor status, breast surgical type (conservation surgery vs. total mastectomy), differentiation of the tumor type, use of chemotherapy, and administration of adjuvant radiotherapy.
The endpoint of the study was all-cause death in chronic pain patients with BC who received long-term tramadol therapy before the index BC diagnosis date.
Six-hundred and twenty-four patients, including 520 long-term tramadol users (cases) and 104 nontramadol users (control group), were included in the study. Multivariate Cox regression analysis found that the group that used tramadol before a BC diagnosis exhibited less favorable prognostic factors for OS (adjusted hazard ratio [aHR] 3.45 for all-cause death between tramadol users and nonusers, 95% CI 2.36-5.04, P <.001). The only variable that was associated with an increase in all-cause death was age. The aHRs of all-cause mortality was 1.6 for those aged 66 to 75 years (95% CI 1.03-2.46), 2.6 for those aged 76 to 85 years (95% CI 1.63-4.17), and 5.09 for those aged older than 85 years (95% CI 2.33-11.12). Further analysis of the 5-year OS curves for the long-term tramadol users versus nonusers were 82.92% versus 52.42%, respectively (P <.001).
Although not definitely conclusive, pharmacists should be aware of the potential risk of increased mortality associated with prior long-term use of tramadol for chronic pain in patients with BC.
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