Dataset Information

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

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.

SUBMITTER: Zeng C

PROVIDER: S-EPMC6439672 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zeng Chao C Dubreuil Maureen M LaRochelle Marc R MR Lu Na N Wei Jie J Choi Hyon K HK Lei Guanghua G Zhang Yuqing Y

JAMA 20190301 10

<h4>Importance</h4>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.<h4>Objective</h4>To examine the association of tramadol prescription with all-cause mortality among patients with osteoarthritis.<h4>Design, setting, and participants</h4>Seq ...[more]

PMID: 30860559

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Project description:BackgroundThe use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine.MethodsUsing administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death.ResultsOverall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0-6.7) to 8.1 (4.9-11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0-1.4) to 1.5 (1.3-1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7-3.7) and HR (95% CI) of 1.7 (1.3-2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4-3.4) and 1.7 (0.2-3.3), respectively, and HRs (95% CI) of 1.6 (1.2-2.0) and 1.4 (1.1-1.9), respectively. No differences were observed between tramadol and NSAIDs for all events.ConclusionsOA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.

Project description:BackgroundThis study was to explore the relationship between cardiovascular health (CVH) and the risk of all-cause mortality in patients with osteoarthritis (OA).MethodsThis cohort study retrieved the data of 3642 patients with OA aged ≥ 20 years from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). CVH was evaluated based on Life's Essential 8 (LE8) includes diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The outcome of all-cause mortality was assessed using the death certificate records of participants from the National Death Index. Variables that might affect all-cause mortality were used as covariates. The weighted univariate COX proportional hazards model was used to explore the association between each covariate and all-cause mortality. The weighted univariate and multivariate COX proportional hazards models were used to explore the association between different CVH levels and all-cause mortality. A restricted cubic spline (RCS) curve was plotted to show the association between different CVH levels and all-cause mortality in OA patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated.ResultsFindings show that people with moderate CVH (HR = 0.67, 95% CI = 0.45-0.98) and high CVH (HR = 0.47, 95% CI = 0.26-0.87) were associated with reduced risk of all-cause mortality in patients with OA. The HR of all-cause mortality in patients with OA decreased by 0.12 as per 10 points increase of LE8 score (HR = 0.81, 95% CI = 0.73-0.90). The RCS curve revealed that the HR of all-cause mortality decreased with the increase in LE8 score. The survival probability of patients in the high CVH group was higher than the moderate CVH group and low CVH group (p = 0.002).ConclusionModerate-to-high CVH is associated with a decreased risk of all-cause mortality in patients with OA. These findings might provide a reference for the formulation of prognosis improvement strategies for the management of patients with OA.

Project description:ObjectiveTramadol 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.DesignAmong 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.ResultsAmong 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.ConclusionsIn 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.

Project description:BackgroundThe newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA.MethodsWe extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects.ResultsIn total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices.ConclusionsThis study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.

Dataset Information

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

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

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

Similar Datasets

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