Table 2. Baseline Characteristics of Propensity Score–Matched Patients With Osteoarthritis in a Study Comparing the Association of Tramadol and Other Analgesics With All-Cause Mortalitya .
| Nonselective NSAIDs | COX-2 Inhibitors | Weak Opioid | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tramadol | Naproxen | Standardized Differences | Tramadol | Diclofenac | Standardized Differences | Tramadol | Celecoxib | Standardized Differences | Tramadol | Etoricoxib | Standardized Differences | Tramadol | Codeine | Standardized Differences | |
| Participants, No. | 12 397 | 12 397 | 6512 | 6512 | 5674 | 5674 | 2946 | 2946 | 16 922 | 16 922 | |||||
| Demographics | |||||||||||||||
| Age, mean (SD), y | 69.4 (9.6) | 69.4 (9.5) | 0.00 | 70.3 (9.6) | 70.3 (9.5) | 0.00 | 69.9 (9.5) | 69.8 (9.5) | 0.01 | 68.9 (9.4) | 68.9 (9.4) | 0.00 | 70.9 (9.5) | 71.0 (9.5) | 0.00 |
| Socioeconomic deprivation index score, mean (SD)b | 2.5 (1.4) | 2.5 (1.4) | 0.01 | 2.5 (1.4) | 2.5 (1.4) | 0.01 | 2.6 (1.4) | 2.6 (1.4) | 0.01 | 2.5 (1.4) | 2.5 (1.4) | 0.03 | 2.5 (1.3) | 2.5 (1.4) | 0.01 |
| Women, % | 59.2 | 59.6 | 0.01 | 61.5 | 62.5 | 0.02 | 65.5 | 65.2 | 0.01 | 62.5 | 62.2 | 0.01 | 60.8 | 60.5 | 0.01 |
| BMI, mean (SD) | 29.1 (5.7) | 29.2 (5.6) | 0.01 | 28.7 (5.6) | 28.8 (5.6) | 0.01 | 28.6 (5.5) | 28.6 (5.3) | 0.00 | 28.7 (5.7) | 28.6 (5.3) | 0.00 | 28.8 (5.5) | 28.8 (5.5) | 0.01 |
| Osteoarthritis duration, mean (SD), y | 6.8 (6.8) | 6.8 (6.6) | 0.00 | 6.4 (6.8) | 6.4 (6.8) | 0.00 | 6.6 (6.4) | 6.6 (6.6) | 0.00 | 6.3 (6.3) | 6.3 (6.3) | 0.00 | 7.2 (7.0) | 7.1 (6.8) | 0.00 |
| Lifestyle factors | |||||||||||||||
| Drinking alcohol, % | |||||||||||||||
| None | 19.1 | 19.2 | 0.00 | 20.9 | 21.9 | 0.02 | 21.6 | 21.5 | 0.00 | 20.5 | 20.7 | 0.00 | 20.0 | 20.2 | 0.00 |
| Past | 2.8 | 2.8 | 0.00 | 2.4 | 2.5 | 0.00 | 2.6 | 2.4 | 0.02 | 2.9 | 2.4 | 0.03 | 2.9 | 3.0 | 0.01 |
| Current | 78.1 | 78.0 | 0.00 | 76.7 | 75.7 | 0.02 | 75.7 | 76.1 | 0.01 | 76.6 | 76.8 | 0.01 | 77.1 | 76.8 | 0.01 |
| Smoking status, % | |||||||||||||||
| None | 53.5 | 53.7 | 0.00 | 54.8 | 54.1 | 0.01 | 56.2 | 55.7 | 0.01 | 57.8 | 56.4 | 0.03 | 54.9 | 55.1 | 0.01 |
| Past | 33.9 | 33.7 | 0.00 | 32.4 | 32.9 | 0.01 | 29.6 | 30.0 | 0.01 | 30.9 | 31.9 | 0.02 | 34.0 | 33.9 | 0.00 |
| Current | 12.6 | 12.6 | 0.00 | 12.8 | 12.9 | 0.00 | 14.2 | 14.3 | 0.00 | 11.3 | 11.6 | 0.01 | 11.1 | 11.0 | 0.01 |
| Comorbidity, % | |||||||||||||||
| CKD | |||||||||||||||
| No CKD | 87.1 | 87.1 | 0.00 | 91.2 | 91.3 | 0.01 | 96.5 | 96.3 | 0.01 | 92.6 | 93.0 | 0.01 | 87.4 | 87.1 | 0.01 |
| Stage 1 | 0.1 | 0.1 | 0.01 | 0.0 | 0.1 | 0.01 | 0.1 | 0.0 | 0.02 | 0.1 | 0.1 | 0.01 | 0.1 | 0.1 | 0.00 |
| Stage 2 | 1.5 | 1.6 | 0.01 | 0.9 | 1.0 | 0.01 | 0.5 | 0.4 | 0.01 | 0.7 | 0.8 | 0.01 | 1.0 | 1.0 | 0.01 |
| Stage 3 | 10.1 | 10.1 | 0.00 | 6.4 | 6.2 | 0.01 | 1.8 | 2.0 | 0.01 | 5.5 | 5.1 | 0.02 | 9.7 | 9.9 | 0.01 |
| Stage 4 | 0.4 | 0.4 | 0.00 | 0.3 | 0.3 | 0.00 | 0.1 | 0.1 | 0.01 | 0.3 | 0.3 | 0.00 | 0.6 | 0.6 | 0.01 |
| Stage 5 | 0.3 | 0.2 | 0.01 | 0.3 | 0.3 | 0.00 | 0.4 | 0.4 | 0.01 | 0.2 | 0.2 | 0.02 | 0.4 | 0.4 | 0.00 |
| Stage unknown | 0.6 | 0.5 | 0.00 | 0.8 | 0.8 | 0.01 | 0.6 | 0.8 | 0.02 | 0.6 | 0.6 | 0.00 | 0.8 | 0.8 | 0.00 |
| Hypertension | 52.1 | 52.4 | 0.01 | 52.5 | 52.9 | 0.01 | 47.4 | 48.1 | 0.01 | 47.8 | 47.8 | 0.00 | 54.2 | 54.6 | 0.01 |
| Other circulatory disease | 32.7 | 32.4 | 0.01 | 32.3 | 32.5 | 0.00 | 34.9 | 34.1 | 0.02 | 33.1 | 31.7 | 0.03 | 36.4 | 36.7 | 0.01 |
| Ischemic heart disease | 14.2 | 14.6 | 0.01 | 18.0 | 18.0 | 0.00 | 17.9 | 18.1 | 0.01 | 13.1 | 13.7 | 0.02 | 18.0 | 18.2 | 0.00 |
| Hyperlipidemia | 18.4 | 18.2 | 0.00 | 17.2 | 17.2 | 0.00 | 14.1 | 14.9 | 0.02 | 16.5 | 16.3 | 0.01 | 18.3 | 18.3 | 0.00 |
| Anxiety | 15.8 | 15.6 | 0.02 | 15.2 | 14.6 | 0.01 | 17.2 | 17.6 | 0.01 | 15.3 | 15.1 | 0.01 | 15.7 | 15.7 | 0.01 |
| Diabetes | 14.6 | 14.5 | 0.00 | 13.2 | 13.8 | 0.02 | 11.7 | 11.4 | 0.01 | 11.2 | 10.8 | Diabetes | 14.6 | 14.5 | 0.00 |
| Depression | 14.4 | 14.5 | 0.00 | 13.7 | 13.9 | 0.01 | 15.3 | 15.2 | 0.00 | 14.5 | 14.8 | 0.01 | 13.5 | 13.7 | 0.01 |
| Varicose veins | 14.0 | 14.1 | 0.00 | 12.9 | 13.1 | 0.01 | 14.8 | 14.5 | 0.01 | 15.6 | 15.2 | 0.01 | 14.7 | 14.9 | 0.01 |
| Angina | 9.4 | 9.7 | 0.01 | 12.6 | 12.7 | 0.01 | 13.3 | 13.5 | 0.00 | 9.9 | 10.0 | 0.01 | 12.5 | 12.5 | 0.00 |
| Peptic ulcer | 6.5 | 6.1 | 0.01 | 8.9 | 8.6 | 0.01 | 8.9 | 8.8 | 0.00 | 6.1 | 6.6 | 0.02 | 7.8 | 7.9 | 0.00 |
| Pneumonia or infection | 7.3 | 7.2 | 0.00 | 7.6 | 7.6 | 0.00 | 9.5 | 9.2 | 0.01 | 8.8 | 8.4 | 0.02 | 7.9 | 8.1 | 0.01 |
| Atrial fibrillation | 4.8 | 4.5 | 0.02 | 5.6 | 5.3 | 0.01 | 4.8 | 4.7 | 0.01 | 3.6 | 3.9 | 0.01 | 7.8 | 8.0 | 0.01 |
| Chronic obstructive pulmonary disease | 5.0 | 4.8 | 0.01 | 6.0 | 5.5 | 0.02 | 5.5 | 5.1 | 0.02 | 5.0 | 4.2 | 0.04 | 5.8 | 5.9 | 0.00 |
| Myocardial infarction | 4.9 | 5.0 | 0.01 | 6.2 | 6.2 | 0.00 | 5.6 | 5.8 | 0.01 | 4.3 | 4.7 | 0.02 | 6.6 | 6.6 | 0.00 |
| Venous thromboembolism | 4.0 | 3.9 | 0.01 | 4.8 | 4.5 | 0.02 | 4.9 | 4.9 | 0.00 | 4.2 | 3.8 | 0.02 | 5.1 | 5.0 | 0.00 |
| Congestive heart failure | 2.8 | 2.6 | 0.02 | 4.5 | 4.3 | 0.01 | 4.6 | 4.5 | 0.00 | 3.3 | 3.2 | 0.01 | 4.8 | 4.8 | 0.00 |
| Transient ischemic attack | 3.2 | 3.3 | 0.01 | 4.2 | 4.1 | 0.01 | 4.0 | 4.0 | 0.00 | 2.1 | 2.7 | 0.04 | 4.2 | 4.2 | 0.00 |
| Stroke | 3.3 | 3.2 | 0.00 | 3.7 | 3.9 | 0.01 | 3.6 | 3.6 | 0.00 | 2.5 | 2.6 | 0.01 | 4.2 | 4.3 | 0.01 |
| Medication, % | |||||||||||||||
| Other NSAIDsc | 85.7 | 86.2 | 0.02 | 73.2 | 74.1 | 0.02 | 90.6 | 91.3 | 0.03 | 94.7 | 94.1 | 0.03 | 88.0 | 87.8 | 0.01 |
| Antihypertensive | 67.0 | 67.6 | 0.01 | 67.6 | 68.5 | 0.02 | 68.2 | 68.3 | 0.00 | 64.8 | 65.1 | 0.01 | 70.1 | 70.5 | 0.01 |
| Statin | 47.6 | 47.9 | 0.01 | 42.4 | 42.6 | 0.01 | 33.7 | 34.2 | 0.01 | 39.5 | 39.5 | 0.00 | 47.0 | 47.2 | 0.00 |
| Aspirin | 36.1 | 36.7 | 0.01 | 37.3 | 37.4 | 0.00 | 34.1 | 34.9 | 0.02 | 30.2 | 31.3 | 0.02 | 40.0 | 40.3 | 0.01 |
| Other opioidsc | 35.4 | 35.9 | 0.01 | 32.0 | 32.9 | 0.02 | 39.6 | 39.5 | 0.00 | 33.3 | 32.5 | 0.02 | 17.3 | 17.1 | 0.00 |
| ACE inhibitors | 36.7 | 36.9 | 0.01 | 34.4 | 35.3 | 0.02 | 28.6 | 28.9 | 0.01 | 28.8 | 29.2 | 0.01 | 39.0 | 39.1 | 0.00 |
| Benzodiazepines | 35.7 | 35.8 | 0.00 | 33.1 | 33.4 | 0.01 | 39.9 | 39.7 | 0.01 | 39.1 | 38.1 | 0.02 | 34.8 | 34.7 | 0.00 |
| Calcium channel blockers | 34.9 | 35.0 | 0.00 | 34.5 | 35.1 | 0.01 | 32.3 | 32.4 | 0.00 | 30.8 | 30.8 | 0.00 | 37.5 | 37.5 | 0.00 |
| β-Receptor inhibitor | 35.8 | 36.0 | 0.00 | 34.5 | 35.3 | 0.02 | 35.2 | 35.6 | 0.01 | 34.2 | 34.0 | 0.00 | 38.9 | 39.1 | 0.00 |
| Loop diuretics | 17.9 | 18.0 | 0.00 | 21.6 | 21.3 | 0.01 | 24.8 | 25.0 | 0.00 | 19.1 | 20.0 | 0.02 | 23.1 | 23.1 | 0.00 |
| Glucocorticoids | 22.7 | 22.9 | 0.00 | 21.3 | 21.0 | 0.01 | 23.9 | 22.7 | 0.03 | 22.6 | 23.2 | 0.01 | 24.1 | 24.0 | 0.00 |
| SSRI | 22.1 | 22.5 | 0.01 | 18.7 | 19.0 | 0.01 | 21.4 | 21.0 | 0.01 | 23.2 | 22.5 | 0.02 | 20.2 | 20.4 | 0.01 |
| Nitrates | 13.5 | 13.7 | 0.01 | 15.5 | 15.7 | 0.01 | 16.7 | 17.2 | 0.01 | 12.7 | 12.8 | 0.01 | 16.8 | 16.8 | 0.00 |
| Angiotensin receptor blocker | 14.2 | 14.3 | 0.00 | 12.7 | 12.6 | 0.00 | 8.8 | 8.9 | 0.00 | 11.8 | 12.1 | 0.01 | 14.1 | 14.2 | 0.00 |
| Potassium-sparing diuretics | 7.6 | 7.6 | 0.00 | 10.5 | 10.5 | 0.00 | 13.8 | 13.5 | 0.01 | 10.6 | 10.6 | 0.00 | 10.3 | 10.3 | 0.00 |
| Antidiabetic | 10.2 | 10.2 | 0.00 | 9.6 | 10.0 | 0.01 | 8.4 | 8.6 | 0.01 | 8.4 | 7.9 | 0.02 | 10.9 | 11.0 | 0.00 |
| Anticoagulants | 6.4 | 6.1 | 0.01 | 7.6 | 6.9 | 0.03 | 6.3 | 6.2 | 0.00 | 4.9 | 4.9 | 0.00 | 10.1 | 10.1 | 0.00 |
| Thiazide-like diuretics | 5.5 | 5.5 | 0.00 | 5.9 | 5.9 | 0.00 | 5.6 | 5.9 | 0.01 | 6.7 | 7.0 | 0.01 | 6.3 | 6.4 | 0.00 |
| SNRI | 5.8 | 6.0 | 0.01 | 4.3 | 4.6 | 0.01 | 5.5 | 5.4 | 0.00 | 5.7 | 5.9 | 0.01 | 5.2 | 5.3 | 0.01 |
| Health care utilization, mean (SD)d | |||||||||||||||
| Hospitalizations | 0.7 (1.3) | 0.7 (1.4) | 0.02 | 0.6 (1.1) | 0.6 (1.3) | 0.01 | 0.4 (1.0) | 0.4 (1.0) | 0.02 | 0.5 (1.0) | 0.4 (1.0) | 0.04 | 0.8 (1.5) | 0.8 (1.6) | 0.01 |
| General practice visits | 12.8 (10.0) | 12.7 (10.3) | 0.01 | 12.8 (9.7) | 12.9 (10.4) | 0.01 | 14.1 (10.7) | 13.9 (11.1) | 0.02 | 13.0 (9.7) | 12.8 (9.2) | 0.02 | 14.2 (11.5) | 14.1 (10.8) | 0.01 |
| Specialist referrals | 1.3 (1.6) | 1.3 (1.7) | 0.01 | 1.0 (1.4) | 1.0 (1.4) | 0.01 | 1.0 (1.3) | 1.0 (1.4) | 0.00 | 1.0 (1.4) | 1.0 (1.4) | 0.00 | 1.3 (1.6) | 1.3 (1.6) | 0.00 |
Abbreviations: ACE, angiotensin-converting enzyme; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CKD, chronic kidney disease; COX-2, cyclooxygenase 2; NSAID, nonsteroidal anti-inflammatory drug; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
a
The time block, site of osteoarthritis, and comorbidities occurring in <5% of patients are presented in the Supplement.
b
The socioeconomic deprivation index score (ie, Townsend Deprivation Index) ranged from 1 (least deprived) to 5 (most deprived).
c
Other NSAID or opioid prescriptions prior to the index date.
d
Frequency during the 2 years before index date.