Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Background: Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). Methods: We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. Results: A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). Conclusion: PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

Estimates of Chronic Kidney Diseases Associated with Proton-Pump Inhibitors Using a Retrospective Hospital-Based Cohort in Thailand.

Purpose: Potential adverse outcomes of Proton pump inhibitors (PPIs) have increasingly been reported. The potential risks to PPIs include hypomagnesemia and chronic kidney disease (CKD). Unlike a real-world electronic medical record (RW-EMR) with active-comparator design, claim databases and special population cohort with non-user design, using in previous studies, resulted in a wide range of strength of association with indication bias. This study aimed to measure the total effect of association between PPIs use and CKD incidence using Thai RW-EMR. Patients and Methods: A retrospective hospital-based cohort was applied into this study. Electronic medical records and administrative data of out- and inpatient were retrieved from October 1st, 2010 to September 30th, 2017. On-treatment with grace period as well as propensity score matching was used in data analysis. Cox proportional hazard models were applied to evaluate the PPIs-CKD association. Results: Of all 63,595 participants, a total of 59,477 new PPIs and 4118 Histamine 2-receptor antagonist (H2RA) users were eligible for follow-up. As compared with H2RA, the PPI users were non-elderly and more likely being female. The association of PPIs with CKD was statistically significant (adjusted hazard ratio [HR] = 3.753, 95% CI = 2.385-5.905). The HR were not statistically different by concomitant use PPIs with NSAIDs and by medication possession ratio levels. Conclusion: The association between PPIs and CKD incidence was statistically significant in this hospital-based cohort. However, self-treatment with over-the-counter PPIs, as well as, smoking, drinking alcohol and body mass index could not be fully retrieved, affecting the estimation of treatment effect.