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Association Of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis

Chao Zeng, Maureen Dubreuil, Marc R. Larochelle, Na Lu, Jie Wei, Hyon K Choi, Guanghua Lei, Yuqing Zhang
Published 2019 · Medicine
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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.
This paper references
Multiple imputation for nonresponse in surveys
Donald B. Rubin (1987)
Perforated peptic ulcer and short-term mortality among tramadol users.
Marie Louise Tørring (2008)
A 15‐year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom
Teng-Chou Chen (2018)
Trends in prescription of opioids from 2003-2009 in persons with knee osteoarthritis.
Elizabeth A. Wright (2014)
Polypharmacy and adverse outcomes after hip fracture surgery
Maria Härstedt (2016)
Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review.
Savannah R. Smith (2016)
Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities.
J. N. Katz (2016)
OARSI guidelines for the non-surgical management of knee osteoarthritis.
Timothy E. McAlindon (2014)
Medication fall risk in old hospitalized patients: a retrospective study.
Maria José Martins da Costa-Dias (2014)
Checking the Cox model with cumulative sums of martingale-based residuals
D. Lin (1993)
Tramadol for noncancer pain and the risk of hyponatremia.
Jean-Pascal Fournier (2015)
Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis
Nicholas R Latimer (2009)
CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016.
Deborah Dowell (2016)
An application of propensity score matching using claims data.
John D Seeger (2005)
Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.
Jean-Pascal Fournier (2015)
Osteoarthritis. Lancet. 2015;386(9991):376-387
S Glyn-Jones (2015)
Comparison of fatal poisonings by prescription opioids.
Margareeta Häkkinen (2012)
The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults
Nicole Seleno (2011)
Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures.
Sameer Hassamal (2018)
Opioid Prescription, Morbidity, and Mortality in United States Dialysis Patients.
Paul L. Kimmel (2017)
Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition.
David S. Jevsevar (2013)
The comparative safety of analgesics in older adults with arthritis.
Daniel H. Solomon (2010)
Imputation for Nonresponse in Surveys
Rubin DB.Multiple (1987)
American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.
Marc C. Hochberg (2012)
Drugs and other chemicals involved in fatal poisoning in England and Wales during 2000–2011
Simon James Handley (2014)
Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks
Carmelo Scarpignato (2015)
Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial.
André D Beaulieu (2008)
Trends in opioid analgesic abuse and mortality in the United States.
Richard C Dart (2015)
Pharmacology and Clinical Experience with Tramadol in Osteoarthritis
Warren A. Katz (2012)
Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study
Blánaid Hicks (2018)
Treatment effects in the presence of unmeasured confounding: dealing with observations in the tails of the propensity score distribution--a simulation study.
Til Stürmer (2010)
Increasing Prescription of Opiates and Mortality in Patients With Inflammatory Bowel Diseases in England
Nicholas E Burr (2018)
Impaired Mobility, ASA Status and Administration of Tramadol are Risk Factors for Postoperative Delirium in Patients Aged 75 Years or More After Major Abdominal Surgery
Antoine Brouquet (2010)
Fatal unintentional intoxications with tramadol during 1995-2005.
Micaela Tjäderborn (2007)
Fracture risk associated with the use of morphine and opiates.
Peter Vestergaard (2006)
Tramadol deaths in Northern Ireland: a review of cases from 1996 to 2012.
Chandalar Randall (2014)
Trends in opioid analgesic abuse and mortality in the United States.
Richard C Dart (2015)
Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain.
W. A. Ray (2016)
Cause-specific mortality in patients with psoriatic arthritis and rheumatoid arthritis
Alexis Ogdie (2017)

This paper is referenced by
Osteoarthritis Year in Review 2019: Epidemiology and Therapy.
Margreet Kloppenburg (2020)
Thiazide diuretics and risk of knee replacement surgery among patients with knee osteoarthritis: a general population-based cohort study.
Jie Wei (2019)
Tramadol and Mortality in Patients With Osteoarthritis-Reply.
Guanghua Lei (2019)
Impact of orally administered tramadol combined with self-selected music on adult outpatients with burns undergoing dressing change: A randomized controlled trial.
Xiu-Hang Zhang (2019)
Tramadol and Mortality in Patients With Osteoarthritis.
David T Felson (2019)
Opioid prescription practices for patients discharged from the emergency department with acute musculoskeletal fractures.
Garrick Mok (2020)
Efficacy and harms of long-term opioid therapy in chronic non-cancer pain: Systematic review and meta-analysis of open-label extension trials with a study duration ≥ 26 weeks.
Paul Bialas (2019)
Preoperative Pain Management: Is Tramadol a Safe Alternative to Traditional Opioids Before Total Hip Arthroplasty?
Joshua A Bell (2020)
Opioid Use After Total Knee Arthroplasty: Does Tramadol Have Lower Risk Than Traditional Opioids?
David E Demik (2020)
Outpatient Readmission in Rheumatology: A Machine Learning Predictive Model of Patient’s Return to the Clinic
Alfredo Madrid-García (2019)
Use of opioids for chronic non-cancer pain.
Vicente Palop Larrea (2020)
Des recommandations sur la prise en charge de la coxarthrose: lecture critique
Magda Choueiri (2019)
Association of Tramadol Use With Risk of Hip Fracture.
Jie Wei (2020)
The epidemiology of regular opioid use and its association with mortality: Prospective cohort study of 466 486 UK biobank participants
Gary John Macfarlane (2020)
Opioids and Cannabinoids for Osteoarthritis: Either, Both, or Neither
Ariane Barbacki (2020)
Treating postoperative pain? Avoid tramadol, long-acting opioid analgesics and long-term use
Georgia C. Richards (2019)
Using Propensity Score Methods to Create Target Populations in Observational Clinical Research.
Laine E Thomas (2020)
Management of osteoarthritis during COVID‐19 pandemic
Enrico Ragni (2020)
Patterns of pharmacological treatment of patients with migraine, tension-type headache, and cluster headache in a large group of patients in Colombia, 2019
Jorge Enrique Machado-Alba (2020)
Association of Tramadol with Risk of Myocardial Infarction Among Patients with Osteoarthritis.
Jie Wei (2019)
Why are we still using opioids for osteoarthritis?
Kevin Yip (2019)
Toward wiping out osteoarthritis in China: research highlights
Zhi-zhong Ye (2020)
Usual care including home exercise with versus without spa therapy for chronic low back pain: protocol for the LOMBATHERM’ study, a multicentric randomised controlled trial
Romain J Forestier (2020)
2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.
Sharon L. Kolasinski (2020)
Towards defining the safer use of opioids in rheumatology
Seoyoung C. Kim (2019)
Opioids for chronic low back pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least four weeks double-blind duration.
Frank Petzke (2019)
Risk of opioid misuse in people with cancer and pain and related clinical considerations: a qualitative study of the perspectives of Australian general practitioners
Tim Luckett (2020)
Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis
Eugene J Kucharz (2019)
Empfehlungen der zweiten Aktualisierung der Leitlinie LONTS
Winfried Häuser (2020)
Translating the dose response into risk and benefit.
John B Warren (2019)
Opioid Treatments for Chronic Pain
Roger Chou (2020)
Efficacy and Safety of Naproxen vs Opioids for the Treatment of Musculoskeletal Pain
Stephen A. Brunton (2019)
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