Association of tramadol with risk of myocardial infarction among patients with osteoarthritis

J Wei; M J Wood; M Dubreuil; G Tomasson; M R LaRochelle; C Zeng; N Lu; J Lin; H K Choi; G Lei; Y Zhang

doi:10.1016/j.joca.2019.10.001

Association of tramadol with risk of myocardial infarction among patients with osteoarthritis

Osteoarthritis Cartilage. 2020 Feb;28(2):137-145. doi: 10.1016/j.joca.2019.10.001. Epub 2019 Oct 16.

Authors

J Wei¹, M J Wood², M Dubreuil³, G Tomasson⁴, M R LaRochelle⁵, C Zeng⁶, N Lu⁷, J Lin⁸, H K Choi⁹, G Lei¹⁰, Y Zhang¹¹

Affiliations

¹ Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
² Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
³ Boston University School of Medicine, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA. Electronic address: [email protected].
⁴ Department of Public Health Sciences, University of Iceland, Stapi Hringbraut, 101 Reykjavik, Iceland. Electronic address: [email protected].
⁵ Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, MA, USA. Electronic address: [email protected].
⁶ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: [email protected].
⁷ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Arthritis Research Canada, Richmond, British Columbia, Canada. Electronic address: [email protected].
⁸ Department of Orthopaedic Surgery, Peking University People's Hospital, Beijing, China. Electronic address: [email protected].
⁹ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
¹⁰ Department of Orthopaedic Surgery, Peking University People's Hospital, Beijing, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: [email protected].
¹¹ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].

Abstract

Objective: Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. We aimed to examine the association of tramadol with risk of myocardial infarction (MI) among patients with OA.

Design: Among OA patients aged 50-90 years without history of MI, cancer, or opioid use disorder in The Health Improvement Network database in the United Kingdom (2000-2016), three sequential propensity-score matched cohort studies were assembled, i.e., (1) patients who initiated tramadol or naproxen (negative comparator); (2) patients who initiated tramadol or diclofenac (positive comparator); and (3) patients who initiated tramadol or codeine (a commonly used weak opioid). The outcome was incident MI over six-months.

Results: Among tramadol and naproxen initiators (n = 33,024 in each cohort), 77 (4.8/1000 person-years) and 46 (2.8/1000 person-years) incident MI occurred, respectively. The rate difference (RD) and hazard ratios (HR) for incident MI with tramadol initiation were 1.9 (95% confidence interval [CI] 0.6 to 2.3)/1000 person-years and 1.68 (95% CI 1.16 to 2.41) relative to naproxen initiation, respectively. Among tramadol and diclofenac initiators (n = 18,662 in each cohort), 58 (6.4/1000 person-years) and 47 (5.1/1000 person-years) incident MIs occurred, respectively. The corresponding RD and HR for incident MI were 1.2 (95%CI -2.1 to 14.1)/1000 person-years and 1.24 (95%CI 0.84 to 1.82), respectively. Among tramadol and codeine initiators (n = 42,722 in each cohort), 127 (6.1/1000 person-years) and 103 (5.0/1000 person-years) incident MI occurred, respectively, and the corresponding RD and HR were 1.1 (95%CI:-0.3 to 2.5)/1000 person-years and 1.23 (95%CI:0.95 to 1.60), respectively.

Conclusions: In this population-based cohort of patients with OA, the six-month risk of MI among initiators of tramadol was higher than that of naproxen, but comparable to, if not lower than, those of diclofenac or codeine.

Keywords: Cohort; Myocardial infarction; Osteoarthritis; Tramadol.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Analgesics, Opioid / therapeutic use*
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Codeine / therapeutic use
Diclofenac / therapeutic use
Female
Humans
Incidence
Male
Middle Aged
Myocardial Infarction / epidemiology*
Naproxen / therapeutic use
Osteoarthritis / drug therapy*
Propensity Score
Proportional Hazards Models
Risk Factors
Tramadol / therapeutic use*

Substances

Analgesics, Opioid
Anti-Inflammatory Agents, Non-Steroidal
Diclofenac
Tramadol
Naproxen
Codeine

Abstract

Publication types

MeSH terms

Substances

Grants and funding