Table 4.
Multivariable time-dependent Cox analyses for risk of all-cause mortality and CRC-specific mortality, related to initiation and cumulative dose of PPI use.
| All-cause mortality | CRC-Specific Mortality | ||||
|---|---|---|---|---|---|
| No. of patients | No. of deaths/ No. of person-years | aHRc | No. of deaths/ No. of person-years | aHRc | |
| PPIs nonusersa | 14,610 | 8439/68,015 | 1 (reference) | 6231/68,015 | 1 (reference) |
| Initiation of PPI use | |||||
| New PPI usersa | 7722 | 2603/17,758 | 1.47 (1.40, 1.51) | 1972/17,758 | 1.44 (1.36, 1.53) |
| Continuous PPI usersa | 10,079 | 2143/16,103 | 1.32 (1.24, 1.39) | 1317/16,103 | 1.27 (1.19, 1.36) |
| Cumulative dose, DDDb | |||||
| <112 | 5870 | 799/8663 | 1.11 (1.02, 1.21) | 572/8663 | 1.11 (1.01, 1.22) |
| 112–512 | 5993 | 2069/9565 | 1.92 (1,82, 2.03) | 1652/9565 | 1.96 (1.84, 2.08) |
| ≥512 | 5938 | 1878/15,634 | 1.09 (1.03, 1.16) | 1065/15,634 | 0.99 (0.92, 1.07) |
| Average daily dose, DDD | |||||
| <0.15 | 5950 | 906/13,485 | 0.84 (0.78, 0.91) | 612/10,408 | 0.81 (0.73, 0.89) |
| 0.15–0.75 | 6045 | 1868/9968 | 1.74 (1,64, 1.84) | 1476/9968 | 1.77 (1.66, 1.89) |
| ≥0.75 | 5806 | 1972/10,408 | 1.55 (1.46, 1.65) | 1201/13,485 | 1.42 (1.32, 1.53) |
PPI proton pump inhibitors, DDD defined daily dose, CRC colorectal cancer, aHR multivariable-adjusted hazard ratio.
aPPI nonusers were patients not collecting PPI dispensation after the diagnosis of CRC. Continuous users were patients collecting at least one PPI dispensation both before and after diagnosis; new users were patients not collecting PPI dispensation before diagnosis but collecting at least one PPI dispensation after diagnosis.
bThe cumulative dose of PPI use was calculated based on cumulative DDD of PPI use after diagnosis of CRC, and the average daily dose was calculated as the cumulative DDD divided by the survival time (days from the diagnosis to death).
caHRs were adjusted for age, sex, pre-diagnosis PPI use, tumour site, tumour stage, CRC surgery, maintenance use of low-dose aspirin, maintenance use of non-aspirin NSAIDs, and the Charlson Comorbidity score. aHRs were additionally adjusted for pre-diagnosis PPI use in the analyses related to the cumulative dose and the average daily dose.