Abstract
Proton pump inhibitors (PPIs) are commonly prescribed medications, but their relationship to mortality in colorectal cancer (CRC) remains poorly understood. This study aims to evaluate the association between PPI use and all-cause mortality IN newly diagnosed CRC. This retrospective cohort study utilized electronic medical records from a network comprising over 80 million patients across 57 healthcare organizations in the USA. We identified adult patients with a first-time CRC diagnosis between January 1, 2010, and December 31, 2022, ensuring at least one year of follow-up. Patients were classified as new users or non-users of PPIs at the time of CRC diagnosis. A lag time of 6 months was adopted to minimize protopathic bias. The primary outcome was all-cause mortality. Patients in the study group were matched with patients controls by using 1:1 propensity matching. The analysis included 252,022 patients (126,011 PPI users and 126,011 non-users) matched on propensity scores. PPI users had a higher mortality risk at 1 year (HR = 1.42), 2 years (HR = 1.44), and over the entire follow-up period (HR = 1.40). Sensitivity analyses, which excluded early outcomes, and ancillary analyses, which compared to those on histamine-2 receptor antagonists, confirmed the robustness of these results. Even for former PPI users, the all-cause mortality HR was 1.39. PPI use was associated with an increased risk of all-cause mortality in CRC patients. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of PPI use in this population. The study indicates that PPIs are associated with increased all-cause mortality in CRC. This highlights the need for careful consideration when prescribing PPIs to this population.