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JAMA. 2019 Mar 12;321(10):969-982. doi: 10.1001/jama.2019.1347.

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis.

Author information

1
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
2
Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.
3
Boston University School of Medicine, Boston, Massachusetts.
4
VA Boston Healthcare System, Boston, Massachusetts.
5
Clinical Addiction Research and Education Unit, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts.

Abstract

Importance:

An American Academy of Orthopaedic Surgeons guideline recommends tramadol for patients with knee osteoarthritis, and an American College of Rheumatology guideline conditionally recommends tramadol as first-line therapy for patients with knee osteoarthritis, along with nonsteroidal anti-inflammatory drugs.

Objective:

To examine the association of tramadol prescription with all-cause mortality among patients with osteoarthritis.

Design, Setting, and Participants:

Sequential, propensity score-matched cohort study at a general practice in the United Kingdom. Individuals aged at least 50 years with a diagnosis of osteoarthritis in the Health Improvement Network database from January 2000 to December 2015, with follow-up to December 2016.

Exposures:

Initial prescription of tramadol (n = 44 451), naproxen (n = 12 397), diclofenac (n = 6512), celecoxib (n = 5674), etoricoxib (n = 2946), or codeine (n = 16 922).

Main Outcomes and Measures:

All-cause mortality within 1 year after initial tramadol prescription, compared with 5 other pain relief medications.

Results:

After propensity score matching, 88 902 patients were included (mean [SD] age, 70.1 [9.5] years; 61.2% were women). During the 1-year follow-up, 278 deaths (23.5/1000 person-years) occurred in the tramadol cohort and 164 (13.8/1000 person-years) occurred in the naproxen cohort (rate difference, 9.7 deaths/1000 person-years [95% CI, 6.3-13.2]; hazard ratio [HR], 1.71 [95% CI, 1.41-2.07]), and mortality was higher for tramadol compared with diclofenac (36.2/1000 vs 19.2/1000 person-years; HR, 1.88 [95% CI, 1.51-2.35]). Tramadol was also associated with a higher all-cause mortality rate compared with celecoxib (31.2/1000 vs 18.4/1000 person-years; HR, 1.70 [95% CI, 1.33-2.17]) and etoricoxib (25.7/1000 vs 12.8/1000 person-years; HR, 2.04 [95% CI, 1.37-3.03]). No statistically significant difference in all-cause mortality was observed between tramadol and codeine (32.2/1000 vs 34.6/1000 person-years; HR, 0.94 [95% CI, 0.83-1.05]).

Conclusions and Relevance:

Among patients aged 50 years and older with osteoarthritis, initial prescription of tramadol was associated with a significantly higher rate of mortality over 1 year of follow-up compared with commonly prescribed nonsteroidal anti-inflammatory drugs, but not compared with codeine. However, these findings may be susceptible to confounding by indication, and further research is needed to determine if this association is causal.

PMID:
30860559
DOI:
10.1001/jama.2019.1347
[Indexed for MEDLINE]

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