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A peer-reviewed article of this preprint also exists.
supplementary.pdf (498.05KB )
This version is not peer-reviewed
Submitted:
24 July 2023
Posted:
25 July 2023
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Stroke | Myocardial infarction | |||||
---|---|---|---|---|---|---|
Variables | PPI co-prescription groups (n=8,201) |
PPI non-prescription group (n=61,987) |
P-value | PPI co-prescription group (n=1,216) |
PPI non-prescription group (n=4,751) |
P-value |
Sex | ||||||
Women, n (%) | 3,742 (45.8) | 25,662 (41.4) | <0.001 | 670 (55.1) | 3,043 (64.0) | <0.001 |
Age | 67.28 ± 10.99 | 66.14 ± 11.86 | <0.001 | 69.64 ± 10.26 | 68.06 ± 11.51 | <0.001 |
Aspirin co-prescription | 3,094 (37.8) | 22,810 (36.8) | 0.069 | 982 (80.8) | 3,608 (75.9) | <0.001 |
Comorbidity | ||||||
Hypertension | 6,357 (77.7) | 46,388 (74.8) | <0.001 | 1,080 (58.1) | 4,103 (86.4) | 0.023 |
Diabetes mellitus | 4,041 (49.4) | 32,432 (52.3) | <0.001 | 707 (58.1) | 2,662 (56.0) | 0.185 |
Dyslipidemia | 5,499 (67.3) | 38,245 (61.7) | <0.001 | 917 (75.4) | 3,534 (74.4) | 0.463 |
Smoking history | ||||||
Never smoker | 2,610 (31.9) | 16,837 (27.1) | <0.001 | 341(28.0) | 1,146 (24.1) | 0.020 |
Ex-smoker | 728 (8.9) | 4,643 (7.5) | 106 (8.7) | 389 (8.2) | ||
Current smoker | 1,137 (13.9) | 8,531 (13.8) | 159 (13.1) | 625 (13.2) | ||
BMI (kg/m2) | 24.43± 3.09 | 24.39 ± 3.05 | 0.479 | 24.11±3.1 | 24.41±3.08 | 0.032 |
Total cholesterol level (mg/dL) | 202.52 ± 42.01 | 204.96 ± 45.07 | <0.001 | 205.94 ±44.95 | 207.52± 53.37 | 0.460 |
Stroke | Myocardial infarction | |||
---|---|---|---|---|
Number of events | Relative risk (95% CI) | Number of events | Relative risk (95% CI) | |
Total events | 1448 | 208 | ||
RR of PPIs exposed periods (PPIs co-prescribed periods only) | ||||
PPIs unexposed | 795 | 1 (reference) | 113 | 1 (reference) |
Overall | 653 | 2.09 (1.83-2.38) | 95 | 1.47 (1.02-2.11) |
0~2 weeks | 254 | 1.76 (1.50-2.07) | 32 | 1.30 (0.83-2.04) |
2~4 weeks | 187 | 2.02 (1.68-2.43) | 16 | 0.95 (0.54-1.69) |
4~6 weeks | 90 | 3.02 (2.36-3.86) | 19 | 2.33 (1.32-4.13) |
6~8 weeks | 47 | 2.81 (2.02- 3.92) | 11 | 1.99 (0.98-4.03) |
>8 weeks | 75 | 5.57 (4.06-7.64) | 17 | 3.80 (1.93-7.45) |
RR of PPIs exposed periods (included PPIs washout periods) | ||||
Non-risk periods | 594 | 1 (reference) | 85 | 1 (reference) |
Risk-periods | 854 | 2.47 (2.16-2.81) | 123 | 1.87 (1.31-2.65) |
Type of PPIs | Stroke | Myocardial infarction | |||
---|---|---|---|---|---|
Number of events | Relative risk (95% CI) | Number of events | Relative risk (95% CI) | ||
Omeprazole | PPIs unexposed | 83 | 1 (reference) | 7 | 1 (reference) |
Overall | 54 | 1.84 (1.18-2.86) | 2 | 0.33 (0.47-2.34) | |
Non-risk periods | 64 | 1 (reference) | 5 | 1 (reference) | |
Risk periods including washout periods | 73 | 2.03 (1.34-3.08) | 4 | 1.04 (0.13-8.40) | |
Esomeprazole | PPIs unexposed | 181 | 1 (reference) | 29 | 1 (reference) |
Overall | 192 | 2.75 (2.12-3.57) | 21 | 0.89 (0.36-2.18) | |
Non-risk periods | 128 | 1 (reference) | 23 | 1 (reference) | |
Risk periods including washout periods | 245 | 3.18 (2.45-4.11) | 27 | 1.18 (0.52-2.65) | |
Pantoprazole | PPIs unexposed | 213 | 1 (reference) | 42 | 1 (reference) |
Overall | 151 | 1.61 (1.21-2.13) | 40 | 2.56 (1.46-4.50) | |
Non-risk periods | 175 | 1 (reference) | 35 | 1 (reference) | |
Risk periods including washout periods | 189 | 1.80 (1.37-2.35) | 47 | 2.53 (1.47-4.36) | |
Rabeprazole | PPIs unexposed | 295 | 1 (reference) | 39 | 1 (reference) |
Overall | 197 | 1.88 (1.49-2.36) | 19 | 1.11(0.54–2.24) | |
Non-risk periods | 232 | 1 (reference) | 32 | 1 (reference) | |
Risk periods including washout periods | 260 | 2.02 (1.62-2.52) | 24 | 1.14 (0.54-1.98) | |
Lansoprazole | PPIs unexposed | 121 | 1 (reference) | 21 | 1 (reference) |
Overall | 49 | 1.32 (0.87-2.01) | 11 | 0.58 (0.22-1.52) | |
Non-risk periods | 99 | 1 (reference) | 16 | 1 (reference) | |
Risk periods including washout periods | 71 | 1.63 (1.12-2.38) | 16 | 0.87 (0.33-2.24) | |
Dexlansoprazole | PPIs unexposed | 9 | 1 (reference) | 0 | 1 (reference) |
Overall | 3 | 1.08 (0.18-6.49) | 2 | NA | |
Non-risk periods | 6 | 1 (reference) | 0 | 1 (reference) | |
Risk periods including washout periods | 6 | 3.65 (0.71-8.78) | 2 | NA |
Outcome | Cohort | Patients, n | Observation, person-years | Events | Incidence ratea | HR (95% CI) | P-value |
---|---|---|---|---|---|---|---|
Stroke | PPI | 373 | 240 | 81 | 337.5 | 1.34 (1.01-1.76) | 0.04 |
Non-PPI | 1,051 | 740 | 189 | 255.2 | Reference | ||
Myocardial infarction | PPI | 179 | 133 | 23 | 171.7 | 1.42 (0.79-2.49) | 0.23 |
Non-PPI | 439 | 336 | 43 | 127.8 | Reference |
Analysis | Observation period | Stroke HR (95% CI) |
Myocardial infarction HR (95% CI) |
---|---|---|---|
PS matching 1:4(main analysis) | 12 months | 1.34 (1.01-1.76) | 1.42 (0.79-2.49) |
1:4 | 6 months | 1.42 (1.05-1.90) | 2.15 (1.10-4.13) |
1:1 | 12 months | 1.52 (1.06-2.20) | 1.33 (0.69-2.65) |
1:1 | 6 months | 1.56 (1.07-2.30) | 2.12 (0.95-5.21) |
PS stratification | 12 months | 1.37 (1.08-1.73) | 1.15 (0.71-1.81) |
6 months | 1.43 (1.10-1.84) | 1.69 (0.96-2.92) |
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