Table 1.
Baseline Characteristics of Propensity-score Matched Patients with Knee Osteoarthritis (≥50 years) Initiating PPI (Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, or Esomeprazole) or H2RA
| Propensity-score Matched Study Cohorts* |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Baseline Characteristics | Omeprazole Initiators (N=2,672) | H2RA Initiators (N=2,672) | Pantoprazole Initiators (N=664) | H2RA Initiators (N=664) | Lansoprazole Initiators (N=3,747) | H2RA Initiators (N=3,747) | Rabeprazole Initiators (N=751) | H2RA Initiators (N=751) | Esomeprazole Initiators (N=827) | H2RA Initiators (N=827) |
| Demographics | ||||||||||
| Age, mean (SD), y | 70.5 (9.7) | 70.9 (9.6) | 71.0 (9.7) | 70.5 (9.8) | 70.8 (9.8) | 70.6 (9.7) | 70.5 (9.4) | 70.0 (9.2) | 69.6 (9.7) | 70.2 (9.5) |
| Male (%) | 41.7 | 42.3 | 40.1 | 42.6 | 43.1 | 42.4 | 38.1 | 38.5 | 37.6 | 39.5 |
| Socio-Economic | ||||||||||
| Deprivation Index Score**, mean (SD) | 2.7 (1.4) | 2.7 (1.4) | 2.8 (1.4) | 2.7 (1.4) | 2.8 (1.4) | 2.8 (1.4) | 2.6 (1.3) | 2.7 (1.3) | 2.7 (1.4) | 2.7 (1.4) |
| OA Duration, mean (SD), y | 7.3 (6.8) | 7.4 (6.7) | 6.6 (6.3) | 6.5 (6.1) | 7.2 (6.7) | 7.2 (6.6) | 6.5 (6.0) | 6.6 (6.2) | 7.4 (7.0) | 7.2 (6.6) |
| BMI, mean (SD), kg/m2 | 28.3 (4.7) | 28.3 (4.4) | 28.3 (4.5) | 28.3 (4.7) | 28.2 (4.6) | 28.2 (4.5) | 28.0 (4.7) | 28.2 (4.4) | 28.2 (4.7) | 28.2 (4.6) |
| Lifestyle factors | ||||||||||
| Smoking (%) | ||||||||||
| None | 56.8 | 57.1 | 57.4 | 56.3 | 56.3 | 56.4 | 59.5 | 58.3 | 57.7 | 56.2 |
| Past | 31.4 | 31.7 | 32.2 | 32.7 | 31.8 | 31.7 | 26.0 | 26.6 | 31.8 | 33.5 |
| Current | 11.8 | 11.2 | 10.4 | 11.0 | 11.9 | 11.9 | 14.5 | 15.0 | 10.5 | 10.3 |
| Alcohol Use (%) | ||||||||||
| None | 22.9 | 24.7 | 22.6 | 24.7 | 22.8 | 22.7 | 21.6 | 22.0 | 22.1 | 20.8 |
| Past | 2.9 | 2.8 | 2.7 | 1.7 | 2.9 | 2.6 | 2.8 | 2.8 | 3.4 | 3.0 |
| Current | 74.1 | 72.5 | 74.7 | 73.6 | 74.3 | 74.7 | 75.6 | 75.2 | 74.5 | 76.2 |
| Comorbidities | ||||||||||
| Charlson Index, mean (SD) | 0.8 (1.3) | 0.7 (1.3) | 0.7 (1.3) | 0.6 (1.1) | 0.7 (1.3) | 0.7 (1.3) | 0.5 (1.1) | 0.6 (1.2) | 0.8 (1.3) | 0.8 (1.3) |
| Peptic Ulcer Disease (%) | 6.8 | 7.5 | 12.3 | 12.3 | 7.0 | 7.0 | 9.7 | 8.9 | 12.2 | 10.9 |
| Gastroesophageal reflux disease (%) | 16.5 | 16.5 | 33.3 | 33.3 | 16.7 | 17.4 | 26.8 | 28.0 | 37 | 35.3 |
| Gastritis (%) | 26.9 | 25.4 | 36.6 | 36 | 26.8 | 27.6 | 32.4 | 31.0 | 43.5 | 43.9 |
| Myocardial Infarction (%) | 8.8 | 8.3 | 7.5 | 9.2 | 8.2 | 7.4 | 6.4 | 7.1 | 4.8 | 5.6 |
| Atrial Fibrillation (%) | 7.7 | 7.3 | 9.0 | 9.3 | 8.4 | 8.3 | 5.6 | 6.7 | 6.2 | 6.4 |
| Ischemic Heart Disease (%) | 21.7 | 22.0 | 22.0 | 22.3 | 21.1 | 19.8 | 19.3 | 20.1 | 16.9 | 18.4 |
| Peripheral Vascular Disease (%) | 2.6 | 2.3 | 3.2 | 3.0 | 2.1 | 2.3 | 2.7 | 2.5 | 1.9 | 2.1 |
| Congestive Heart Failure (%) | 6.0 | 5.6 | 6.2 | 6.2 | 5.9 | 5.3 | 6.0 | 5.7 | 3.9 | 4.0 |
| Valvular Heart Disease (%) | 4.7 | 4.1 | 3.0 | 3.8 | 4.1 | 3.7 | 2.3 | 2.0 | 2.3 | 3.1 |
| Transient Ischemic Attack (%) | 5.1 | 4.6 | 5.9 | 5.7 | 5.3 | 5.0 | 5.5 | 4.9 | 4.6 | 5.0 |
| Angina (%) | 13.7 | 14.1 | 14.3 | 14.8 | 13.4 | 12.6 | 14.4 | 15.2 | 12.0 | 14.0 |
| Other Circulatory Disease (%) | 36.8 | 36.0 | 40.5 | 38.7 | 36.1 | 36.1 | 34.9 | 36.0 | 37.0 | 39.4 |
| Stroke (%) | 5.2 | 4.8 | 5.4 | 3.3 | 5.9 | 5.3 | 4.0 | 3.7 | 3.1 | 3.7 |
| Hypertension (%) | 51.9 | 51.6 | 53.3 | 51.4 | 49.9 | 50.8 | 46.9 | 48.3 | 50.8 | 52.4 |
| Chronic Obstructive Pulmonary Disease (%) | 7.4 | 7.1 | 5.7 | 5.0 | 6.8 | 6.8 | 5.2 | 5.1 | 5.9 | 7.4 |
| Chronic Kidney Disease (%) | 10.8 | 9.9 | 8.7 | 8.0 | 10.3 | 9.7 | 3.1 | 3.3 | 9.8 | 9.8 |
| Liver Disease (%) | 2.7 | 2.7 | 1.4 | 1.2 | 2.6 | 3.0 | 1.7 | 2.1 | 2.8 | 2.8 |
| Diabetes (%) | 16.1 | 15.2 | 15.4 | 17.0 | 15.5 | 15.1 | 10.0 | 11.5 | 15.5 | 14.1 |
| Cancer (%) | 13.6 | 13.4 | 12.3 | 11.7 | 13.5 | 13 | 10.8 | 10.7 | 12.8 | 12.2 |
| Pneumonia or Infection (%) | 9.0 | 9.5 | 10.7 | 11.9 | 9.3 | 9.0 | 10.4 | 8.1 | 9.3 | 9.2 |
| Depression (%) | 14.0 | 13.0 | 15.8 | 16.3 | 13.4 | 14.1 | 13.6 | 13.6 | 16.4 | 18.1 |
| Venous Thromboembolism (%) | 4.3 | 4.8 | 4.1 | 4.5 | 4.2 | 4.2 | 4.3 | 3.9 | 3.7 | 3.4 |
| Varicose (%) | 15.3 | 14.3 | 16.0 | 15.8 | 14.4 | 14.2 | 12.8 | 15.4 | 15.7 | 14.8 |
| Inflammatory Conditions (%) | 12.5 | 13.1 | 11.9 | 12.3 | 13 | 12.7 | 11.1 | 11.1 | 12.6 | 12.2 |
| Falls (%) | 15.4 | 16.2 | 17.8 | 17.9 | 15.2 | 15.2 | 16.1 | 14.4 | 16.2 | 17.2 |
| Hip Fracture (%) | 2.0 | 1.9 | 2.0 | 1.4 | 1.7 | 1.7 | 1.2 | 0.8 | 1.7 | 2.1 |
| Hyperlipidemia (%) | 19.3 | 18.2 | 19.7 | 18.4 | 17.9 | 17.9 | 16.2 | 16.6 | 18.5 | 21.3 |
| Dementia (%) | 1.1 | 1.4 | 1.5 | 1.2 | 1.4 | 1.4 | 0.5 | 0.5 | 1.8 | 1.5 |
| Osteoporosis (%) | 10.4 | 11.0 | 12.8 | 15.5 | 10.9 | 10.6 | 10.5 | 10.7 | 10.8 | 12.6 |
| Seizure (%) | 0.8 | 0.8 | 0.5 | 0.5 | 0.6 | 0.7 | 0.4 | 0.4 | 0.6 | 0.2 |
| Trauma (%) | 1.1 | 1.1 | 1.4 | 1.4 | 1.2 | 1.4 | 0.8 | 0.8 | 1.0 | 1.7 |
| Medication | ||||||||||
| Nitrate (%) | 11.6 | 10.7 | 12.3 | 14.9 | 10.8 | 10.3 | 10.3 | 9.9 | 9.2 | 9.6 |
| Antihypertensive Medicine (%) | 61.3 | 60.7 | 61.6 | 62.2 | 59.5 | 60.0 | 56.7 | 59.4 | 61.3 | 61.8 |
| ACE Inhibitors (%) | 27.2 | 25.8 | 26.4 | 25.0 | 26.2 | 25.6 | 20.4 | 21.8 | 24.4 | 24.7 |
| Beta Blockers (%) | 26.8 | 26.0 | 25.9 | 25.9 | 24.8 | 24.4 | 22.2 | 24.4 | 22.1 | 23.7 |
| Calcium Channel Blockers (%) | 24.8 | 24.7 | 25.6 | 26.1 | 23.9 | 24.5 | 20.4 | 22.0 | 23.9 | 25 |
| ARBs (%) | 11.5 | 10.9 | 11.3 | 11.0 | 10.5 | 11.0 | 7.9 | 8.0 | 13.9 | 14.1 |
| Statin (%) | 36.8 | 36.6 | 36.9 | 36.9 | 36.3 | 34.9 | 23.3 | 25.0 | 35.2 | 36.3 |
| Benzodiazepines (%) | 14.7 | 14.4 | 17.8 | 17.5 | 15.3 | 15.2 | 16.0 | 17.0 | 16.6 | 15.7 |
| SSRI (%) | 9.6 | 9.2 | 10.2 | 10.4 | 9.6 | 10.7 | 7.6 | 8.5 | 11.0 | 12.0 |
| SNRI (%) | 1.8 | 1.4 | 2.0 | 2.3 | 1.8 | 1.6 | 1.2 | 1.9 | 1.9 | 1.6 |
| Aspirin (%) | 33.2 | 32.4 | 31.3 | 30.7 | 31.6 | 30.7 | 28.4 | 30 | 26.4 | 30.0 |
| NSAIDs (%) | 44.4 | 44.4 | 45.2 | 47.0 | 46.1 | 45.5 | 52.1 | 53.7 | 38.9 | 40.1 |
| Loop Diuretics (%) | 14.7 | 15.0 | 15.5 | 16.3 | 15.5 | 14.1 | 16.0 | 15.2 | 12.8 | 13.3 |
| HCTZ (%) | 20.4 | 20.1 | 19.6 | 19.0 | 18.8 | 19.8 | 22.1 | 24.0 | 19.1 | 20.7 |
| Potassium Sparing Diuretics (%) | 4.8 | 5.1 | 5.1 | 5.4 | 4.7 | 4.2 | 6.8 | 5.1 | 3.9 | 4.0 |
| DMARDs (%) | 1.8 | 1.5 | 1.5 | 1.5 | 1.7 | 1.7 | 1.5 | 1.5 | 2.2 | 2.1 |
| Glucocorticoids (%) | 11.8 | 11.6 | 12.0 | 10.2 | 12.6 | 13.1 | 10.3 | 11.1 | 11.1 | 10.5 |
| Anticoagulant (%) | 6.2 | 6.2 | 7.5 | 7.2 | 6.0 | 6.2 | 4.3 | 5.6 | 4.7 | 3.9 |
| Opioids (%) | 16.7 | 17.6 | 22.1 | 20.0 | 16.6 | 17.2 | 16.9 | 15.3 | 22.2 | 23.1 |
| Other PPIs (%) | 20.9 | 21.2 | 51.5 | 49.7 | 26.9 | 25.9 | 27.0 | 24.9 | 71.3 | 70.1 |
| Bisphosphonates (%) | 6.5 | 6.4 | 7.2 | 8.0 | 6.3 | 5.8 | 5.2 | 4.7 | 6.4 | 6.7 |
| Antidiabetic Medication | 11.3 | 10.6 | 10.2 | 11.6 | 10.8 | 10.4 | 7.5 | 9.1 | 10.8 | 10.2 |
| Health Care Utilization, mean (SD) | ||||||||||
| General Practice Visits*** | 14.0 (11.6) | 14.1 (11.6) | 15.6 (11.7) | 15.2 (11.1) | 14.2 (11.1) | 14.2 (11.0) | 13.8 (10.2) | 13.8 (10.4) | 16.2 (11.5) | 16.3 (11.9) |
| Hospitalizations*** | 0.8 (1.9) | 0.8 (1.6) | 0.8 (1.7) | 0.9 (1.8) | 0.8 (1.7) | 0.8 (1.9) | 0.4 (1.1) | 0.3 (0.9) | 0.9 (1.9) | 1.0 (1.9) |
| Referrals*** | 1.2 (1.7) | 1.2 (1.8) | 1.4 (1.7) | 1.4 (2.0) | 1.2 (1.7) | 1.2 (1.8) | 0.9 (1.5) | 0.9 (1.3) | 1.5 (1.8) | 1.6 (2.2) |
H2RAs, histamine-2 receptor antagonists; N, number; OA, osteoarthritis; BMI, body mass index; ACE, angiotensin converting enzyme; ARB, Angiotensin II receptor blocker; SSRI, Selective serotonin reuptake inhibitor; SNRI, Serotonin-norepinephrine reuptake inhibitor; NSAIDs, non-steroidal anti-inflammatory drugs; HCTZ, hydrochlorothiazide; DMARDs, disease-modifying antirheumatic drugs; PPI, proton pump inhibitor; H2RA, Histamine-2 receptor antagonist; y, years; SD, standard deviation.
*
A comparison initiator was randomly selected to match to each initiator within 1 -year cohort accrual block.
**
Socio-Economic Deprivation Index Score was measured by the Townsend Deprivation Index, which was grouped into quintiles from 1 (least deprived) to 5 (most deprived).
***
Frequency during the past two years