Table 1.
Basic Characteristics of Propensity-score Matched Patients with Osteoarthritis
| Tramadol vs. Naproxen | Tramadol vs. Diclofenac | Tramadol vs. Codeine | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Tramadol (n=33,024) | Naproxen (n=33,024) | Standardized differences | Tramadol (n=18,662) | Diclofenac (n=18,662) | Standardized differences | Tramadol (n=42,722) | Codeine (n=42,722) | Standardized differences | |
| Demographics | |||||||||
| Age, mean (SD), y | 68.3 (9.6) | 68.4 (9.4) | 0.010 | 69.5 (9.7) | 69.7 (9.5) | 0.023 | 70.1 (9.6) | 70.1 (9.7) | 0.002 |
| Socioeconomic deprivation index, mean (SD)† | 2.7 (1.4) | 2.7 (1.4) | 0.007 | 2.8 (1.4) | 2.9 (1.4) | 0.008 | 2.7 (1.4) | 2.7 (1.3) | 0.001 |
| Female (%) | 61.8 | 62.4 | 0.013 | 64.5 | 65.5 | 0.021 | 64.0 | 64.2 | 0.004 |
| BMI, mean (SD), kg/m2 | 29.0 (5.8) | 29.0 (5.7) | 0.005 | 28.6 (5.7) | 28.7 (5.6) | 0.005 | 28.6 (5.6) | 28.6 (5.5) | <0.001 |
| OA site (%) | |||||||||
| Knee OA | 25.0 | 25.0 | 0.001 | 22.1 | 22.3 | 0.005 | 25.8 | 25.6 | 0.005 |
| Hip OA | 12.9 | 12.9 | 0.001 | 12.5 | 12.7 | 0.006 | 13.4 | 13.3 | 0.004 |
| Hand OA | 5.3 | 5.0 | 0.015 | 4.3 | 4.1 | 0.011 | 5.4 | 5.4 | 0.001 |
| OA duration, mean (SD), y | 7.8 (7.3) | 7.9 (7.3) | 0.002 | 7.6 (7.4) | 7.6 (7.6) | 0.001 | 8.3 (7.6) | 8.3 (7.4) | 0.002 |
| Lifestyle factors | |||||||||
| Alcohol (%) | 0.006 | 0.005 | 0.007 | ||||||
| None | 20.3 | 20.5 | 23.2 | 23.4 | 21.6 | 21.4 | |||
| Past | 2.7 | 2.8 | 2.5 | 2.5 | 2.9 | 2.9 | |||
| Current | 76.9 | 76.7 | 74.2 | 74.1 | 75.4 | 75.7 | |||
| Smoking (%) | 0.007 | 0.009 | 0.004 | ||||||
| None | 53.1 | 52.8 | 53.5 | 53.3 | 54.7 | 54.5 | |||
| Past | 32.6 | 32.8 | 31.3 | 31.2 | 32.7 | 32.9 | |||
| Current | 14.2 | 14.4 | 15.1 | 15.5 | 12.6 | 12.5 | |||
| Comorbidity (%) | |||||||||
| Peptic ulcer | 6.3 | 6.1 | 0.008 | 8.7 | 8.5 | 0.009 | 7.4 | 7.5 | 0.002 |
| Chronic kidney disease | 10.3 | 10.2 | 0.002 | 7.2 | 7.0 | 0.008 | 10.9 | 10.7 | 0.005 |
| Stroke | 3.3 | 3.2 | 0.006 | 3.7 | 3.8 | 0.003 | 4.3 | 4.5 | 0.008 |
| Diabetes | 14.5 | 14.5 | 0.001 | 13.4 | 13.7 | 0.010 | 14.9 | 14.9 | 0.002 |
| Hypertension | 50.0 | 50.3 | 0.006 | 50.9 | 51.7 | 0.017 | 52.9 | 52.8 | 0.002 |
| Liver disease | 2.4 | 2.4 | <0.001 | 2.4 | 2.4 | 0.004 | 2.6 | 2.6 | 0.001 |
| Transient ischemic attack | 3.1 | 3.0 | 0.005 | 3.8 | 3.6 | 0.010 | 4.0 | 4.1 | 0.003 |
| Ischemic heart disease | 9.9 | 9.7 | 0.004 | 12.9 | 12.8 | 0.002 | 12.9 | 12.6 | 0.006 |
| Congestive heart failure | 1.9 | 1.7 | 0.011 | 3.2 | 2.9 | 0.013 | 3.5 | 3.5 | <0.001 |
| Angina | 7.4 | 7.3 | 0.005 | 9.9 | 9.9 | <0.001 | 9.8 | 9.6 | 0.007 |
| Peripheral vascular disease | 1.5 | 1.4 | 0.011 | 2.1 | 1.9 | 0.012 | 1.8 | 1.9 | 0.004 |
| Venous thromboembolism | 3.4 | 3.5 | 0.003 | 3.9 | 3.7 | 0.010 | 4.4 | 4.4 | 0.001 |
| Pneumonia or infection | 7.2 | 7.2 | 0.002 | 7.0 | 6.8 | 0.007 | 8.0 | 7.9 | 0.004 |
| Hyperlipidaemia | 17.0 | 17.3 | 0.007 | 15.5 | 15.9 | 0.010 | 16.9 | 16.8 | 0.003 |
| Dementia | 0.9 | 0.9 | 0.004 | 0.8 | 0.8 | 0.001 | 1.2 | 1.3 | 0.006 |
| Varicose veins | 12.8 | 12.7 | 0.003 | 12.5 | 12.7 | 0.005 | 13.8 | 13.8 | 0.001 |
| Other circulatory disease | 30.3 | 30.1 | 0.004 | 29.1 | 29.2 | 0.001 | 34.0 | 33.8 | 0.003 |
| Depression | 14.7 | 14.9 | 0.006 | 14.1 | 14.0 | 0.004 | 14.0 | 14.0 | 0.001 |
| Chronic obstructive pulmonary disease | 5.4 | 5.3 | 0.002 | 6.2 | 6.0 | 0.007 | 6.2 | 6.2 | 0.003 |
| Atrial fibrillation | 4.1 | 3.7 | 0.020 | 4.7 | 4.3 | 0.019 | 7.0 | 6.9 | 0.002 |
| Anxiety | 16.2 | 16.2 | 0.001 | 15.3 | 15.5 | 0.007 | 16.2 | 16.2 | <0.001 |
| Seizure | 0.5 | 0.5 | 0.001 | 0.5 | 0.4 | 0.001 | 0.5 | 0.5 | 0.006 |
| Sleep disorder or sleep apnea | 1.9 | 1.9 | 0.004 | 1.5 | 1.5 | 0.007 | 1.8 | 1.8 | 0.001 |
| Rheumatoid arthritis | 2.1 | 2.0 | 0.002 | 2.2 | 2.1 | 0.006 | 2.5 | 2.5 | <0.001 |
| Medication (%) | |||||||||
| Other NSAIDs# | 85.0 | 85.1 | 0.003 | 70.3 | 71.7 | 0.031 | 86.4 | 86.2 | 0.006 |
| Other opioids# | 32.8 | 33.1 | 0.006 | 30.3 | 30.4 | 0.002 | 15.6 | 15.7 | 0.001 |
| Aspirin | 33.2 | 33.3 | 0.003 | 34.1 | 34.5 | 0.008 | 36.3 | 36.3 | <0.001 |
| ACE inhibitors | 34.0 | 34.1 | 0.001 | 32.2 | 32.3 | 0.002 | 36.7 | 36.6 | 0.002 |
| Calcium channel blockers | 32.4 | 33.0 | 0.013 | 32.9 | 33.2 | 0.005 | 35.9 | 35.6 | 0.006 |
| Angiotensin receptor blocker | 13.5 | 13.4 | 0.002 | 12.3 | 12.3 | <0.001 | 13.6 | 13.6 | <0.001 |
| Beta receptor inhibitor | 33.4 | 33.4 | <0.001 | 31.8 | 32.3 | 0.011 | 35.9 | 35.9 | 0.001 |
| Statins | 41.0 | 41.5 | 0.010 | 35.6 | 35.9 | 0.006 | 39.9 | 39.8 | 0.002 |
| Loop diuretics | 16.2 | 16.1 | 0.001 | 20.0 | 19.6 | 0.012 | 20.8 | 20.9 | 0.003 |
| Thiazide diuretics | 36.8 | 37.1 | 0.005 | 38.9 | 39.4 | 0.010 | 39.9 | 40.0 | 0.002 |
| Potassium-sparing diuretics | 6.8 | 6.9 | <0.001 | 9.4 | 9.3 | 0.001 | 9.0 | 8.9 | 0.002 |
| Glucocorticoids | 22.6 | 22.7 | 0.003 | 21.1 | 21.2 | 0.001 | 24.2 | 24.0 | 0.003 |
| Nitrates | 11.3 | 11.1 | 0.007 | 12.9 | 12.9 | 0.002 | 13.5 | 13.5 | 0.001 |
| Antidiabetic medicine | 10.4 | 10.4 | <0.001 | 9.8 | 10.0 | 0.005 | 10.7 | 10.6 | 0.002 |
| Anticoagulants | 5.4 | 5.2 | 0.012 | 5.9 | 5.4 | 0.025 | 8.8 | 8.7 | 0.004 |
| Benzodiazepines | 36.1 | 36.6 | 0.011 | 33.5 | 33.8 | 0.007 | 35.5 | 35.3 | 0.004 |
| SSRI | 24.0 | 24.0 | 0.001 | 20.7 | 20.6 | 0.002 | 22.1 | 22.1 | 0.002 |
| SNRI | 6.5 | 6.6 | 0.004 | 5.2 | 5.3 | 0.005 | 5.7 | 5.7 | <0.001 |
| Antiepileptic medicine | 9.1 | 9.3 | 0.005 | 6.9 | 6.9 | <0.001 | 8.5 | 8.5 | <0.001 |
| PPIs | 57.0 | 56.8 | 0.003 | 50.1 | 50.3 | 0.002 | 53.7 | 53.4 | 0.005 |
| H2 blockers | 23.1 | 23.3 | 0.005 | 24.8 | 24.7 | 0.002 | 25.6 | 25.5 | 0.003 |
| Healthcare utilization, mean (SD) | |||||||||
| Hospitalizations‡ | 0.4 (0.8) | 0.4 (0.9) | 0.024 | 0.3 (0.8) | 0.3 (0.9) | 0.030 | 0.5 (1.0) | 0.5 (1.1) | 0.002 |
| General practice visits‡ | 6.9 (5.6) | 6.9 (5.8) | 0.006 | 7.0 (6.0) | 7.0 (6.2) | 0.005 | 7.7 (6.8) | 7.7 (6.5) | 0.006 |
| Specialist referrals‡ | 0.7 (1.1) | 0.7 (1.1) | 0.005 | 0.5 (0.9) | 0.5 (0.9) | 0.003 | 0.7 (1.0) | 0.7 (1.1) | 0.003 |
| Propensity score (SD) | 0.5 (0.2) | 0.5 (0.2) | 0.002 | 0.4 (0.2) | 0.4 (0.2) | 0.002 | 0.6 (0.1) | 0.6 (0.1) | 0.009 |
OA, osteoarthritis; BMI, body mass index; n, number; y, years; SD, standard deviation; NSAID, non-steroidal anti-inflammatory drug; ACE, angiotensin converting enzyme; SSRI, Selective serotonin reuptake inhibitor; SNRI, Serotonin-norepinephrine reuptake inhibitor; PPIs, proton pump inhibitors; H2 blockers, histamine-2 blockers.
†
The Socio-Economic Deprivation Index (i.e., Townsend Deprivation Index) was grouped into quintiles from 1 (least deprived) to 5 (most deprived).
#
Other NSAIDs or opioids means other NSAIDs or opioids use prior to the index date.
‡
Frequency during the past one year.