Why carry out this study?
|
Patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) require long-term nonsteroidal anti-inflammatory drugs (NSAIDs) use. However, the side effects of long-term NSAIDs use limit its benefits in these patients. |
We aimed to assess health burden of cardiovascular events associated with NSAID use in Japanese patients with OA and/or CLBP. |
What was learned from the study?
|
This retrospective database study shows that prolonged NSAID use increases risk of acute myocardial infarction. |
Elderly patients and patients with diabetes, hypertension, and other cardiovascular disease are at increased risk for acute myocardial infarction. |
Plain Language Summary
Digital Features
Introduction
Methods
Study Design and Data Sources
Exposure
Study Outcomes
Statistical Analysis
Ethics Statement
Results
Patient Disposition
Characteristics | All patients (N = 180,371) | Patients < 65 years (N = 165,938) | Patients ≥ 65 years (N = 14,433) |
---|---|---|---|
Age at index date, mean ± SD (years) | 49.3 ± 11.8 | 47.7 ± 10.8 | 68.2 ± 2.8 |
Men, n (%) | 92,650 (51.4) | 86,079 (51.9) | 6571 (45.5) |
Follow-up duration, median (IQR) (days) | 857.0 (433.0, 1460.0) | 884.0 (450.0, 1491.0) | 610.0 (308.0, 1086.0) |
Comorbidities, n (%) | |||
GI disease | 14,285 (7.9) | 12,407 (7.5) | 1878 (13.0) |
Renal disease | 1454 (0.8) | 1183 (0.7) | 271 (1.9) |
CV disease (excluding hypertensive disease) | 24,238 (13.4) | 19,560 (11.8) | 4678 (32.4) |
Hypertension | 39,413 (21.9) | 32,321 (19.5) | 7092 (49.1) |
Diabetes mellitus | 21,240 (11.8) | 17,405 (10.5) | 3835 (26.6) |
NSAIDs as first-line analgesics | 161,152 (89.3%) | 148,146 (89.3) | 13,006 (90.1) |
Patients stratified by treatment duration, mean ± SD (years) | |||
> 0 to ≤ 1 | 152,408 (84.5) | 140,732 (84.8) | 11,676 (80.9) |
> 1 to ≤ 3 | 7449 (4.1) | 6326 (3.8) | 1123 (7.8) |
> 3 to ≤ 5 | 1022 (0.6) | 849 (0.5) | 173 (1.2) |
> 5 | 273 (0.2) | 239 (0.1) | 34 (0.2) |
Consistent use of NSAIDsa, n (%) | 33,795 (21.0) | 29,724 (20.1) | 4071 (31.3) |
Mode of administration of first-line NSAIDs, n (%) | |||
Oral | 145,597 (90.3) | 135,074 (91.2) | 10,523 (80.9) |
Patch | 129,591 (80.4) | 118,328 (79.9) | 11,263 (86.6) |
Other transdermal | 38,648 (24.0) | 35,126 (23.7) | 3522 (27.1) |
Suppository | 18,580 (11.5) | 17,418 (11.8) | 1162 (8.9) |
First-Line NSAID Use
Mode of administration | Treatment duration (years) | ||||
---|---|---|---|---|---|
> 0 to ≤ 1 | > 1 to ≤ 3 | > 3 to ≤ 5 | > 5 | Total | |
Any | 20.7 (27,989/135,036) | 19.0 (4205/22,131) | 36.4 (1171/3221) | 56.3 (430/764) | 21.0 (33,795/161,152) |
Oral alone | 22.2 (4563/20,597) | 15.9 (148/931) | 27.1 (29/107) | 37.5 (6/16) | 21.9 (4746/21,651) |
Patch alone | 55.6 (5449/9804) | 45.5 (625/1375) | 65.8 (77/117) | 70.6 (12/17) | 54.5 (6163/11,313) |
Other transdermal drugs alone | 41.8 (361/864) | 0.0 (0/19) | 0.0 (0/2) | 0.0 (0/0) | 40.8 (361/885) |
Suppository alone | 42.5 (133/313) | 0.0 (0/3) | 0.0 (0/0) | 0.0 (0/0) | 42.1 (133/316) |
Cardiovascular Events
CV events | All patients | |||
---|---|---|---|---|
Na | n | Incidence rate per 10,000 person-years (95% CI) | ||
Total | 160,726 | 355 | 10.27 (9.20, 11.34) | |
Treatment duration, year | < 1 | 134,696 | 241 | 9.68 (8.45, 10.90) |
> 1 to ≤ 3 | 22,058 | 87 | 11.53 (9.11, 13.96) | |
> 3 to ≤ 5 | 3208 | 16 | 10.01 (5.10, 14.91) | |
> 5 | 764 | 11 | 21.66 (8.86, 34.46) | |
Percentage of supply days | < 70% | 127,041 | 312 | 9.84 (8.74, 10.93) |
≥ 70% | 33,685 | 43 | 15.18 (10.64, 19.71) | |
Mode of administration | Oral | 21,607 | 28 | 8.75 (5.51, 11.99) |
Patch | 11,260 | 20 | 16.80 (9.44, 24.16) | |
Other | 127,859 | 307 | 10.18 (9.04, 11.32) | |
Combination of oral and topical | Yes | 69,616 | 129 | 8.87 (7.34, 10.40) |
No | 91,110 | 226 | 11.30 (9.82, 12.77) |
Model variable | Categories | Risk ratio (95% CI) | P value |
---|---|---|---|
Duration of NSAIDs treatment | vs. < 1 year | ||
> 1 to ≤ 3 | 1.03 (0.81, 1.32) | 0.8148 | |
> 3 to ≤ 5 | 0.84 (0.50, 1.39) | 0.4861 | |
> 5 | 1.92 (1.05, 3.52) | 0.0346 | |
Consistent use of NSAIDs | Consistent use of NSAIDs (percentage of supply days ≥ 70%) vs. < 70% | 1.18 (0.85, 1.62) | 0.3257 |
Mode of administration | vs. oral | ||
Patch | 1.20 (0.67, 2.14) | 0.5347 | |
Other | 1.04 (0.70, 1.54) | 0.8598 | |
Combination use | 0.86 (0.70, 1.55) | 0.3324 |
Risk ratio (95% CI) | P value | |
---|---|---|
Age in years, vs. 18 to < 30 | ||
30 to < 40 | 1.46 (0.41, 5.24) | 0.5596 |
40 to < 50 | 4.21 (1.32, 13.41) | 0.0150 |
50 to < 60 | 8.59 (2.73, 26.97) | 0.0002 |
60 to < 70 | 10.72 (3.39, 33.96) | < 0.0001 |
70 to ≤ 75 | 15.80 (4.62, 54.05) | < 0.0001 |
Male gender vs. female | 2.96 (2.31, 3.78) | < 0.0001 |
Baseline GI comorbidities | 1.25 (0.79, 1.98) | 0.3328 |
Baseline renal comorbidities | 0.83 (0.20, 3.40) | 0.7945 |
Baseline CV comorbidities | 2.78 (2.07, 3.73) | < 0.0001 |
Baseline hypertension | 1.56 (1.09, 2.23) | 0.0156 |
Baseline diabetes mellitus | 1.71 (1.18, 2.48) | 0.0049 |
Duration of treatment in years vs. < 1 year | ||
> 1 to ≤ 3 | 1.01 (0.79, 1.30) | 0.9318 |
> 3 to ≤ 5 | 0.80 (0.47, 1.34) | 0.3921 |
> 5 | 1.77 (0.94, 3.35) | 0.0784 |
Chronic use of NSAIDs (percentage of supply days ≥ 70%) vs . < 70% | 1.13 (0.79, 1.60) | 0.5004 |
Mode of administration compared to oral | ||
Patch | 1.16 (0.65, 2.09) | 0.6145 |
Other | 1.03 (0.69, 1.54) | 0.8827 |
Combination use | 0.81 (0.54, 1.22) | 0.3166 |