Longitudinal trajectories unravel the complex interplay of medication, cardiovascular events, chronic kidney disease, and mortality

TL;DR

This study explores how long-term use of proton pump inhibitors affects kidney health and mortality, suggesting a need for closer monitoring of kidney function in users.

Contribution

The study uses process mining on real-world data to uncover disease trajectories linking PPI use to CKD and mortality.

Findings

PPI use is significantly associated with higher subdistribution hazards of CKD and all-cause mortality compared to H2 blockers.

CKD may mediate the trajectory from PPI use to cardiovascular events.

The association between PPI and cardiovascular events is not significant after accounting for mortality as a competing event.

Abstract

Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders, yet concerns persist regarding their association with adverse cardiovascular (CVAE), renal outcomes, and all-cause mortality. We leveraged real-world longitudinal data from the Stockholm CREAtinine Measurements (SCREAM) project to investigate trajectories linking PPI use with chronic kidney disease (CKD), CVAE, and all-cause mortality using a process mining approach. We identified 294,734 new users of PPIs or H2 blockers (H2Bs) with a baseline eGFR ≥ 60 mL/min/1.73 m² and followed them for up to 15 years using a process-mining approach to discover disease trajectories. The association of PPI and CVAE is not significant after accounting for death as a competing event. However, PPI use is significantly associated with a higher subdistribution hazard of CKD and all-cause mortality compared to H2B. Our findings indicate that CKD may act as a mediator in the trajectory PPI→CKD→CVAE, underscore the importance of monitoring renal function in long-term PPI users, and emphasise the need for future prospective trials to clarify cardiovascular risks.

The online version contains supplementary material available at 10.1038/s41598-025-23527-5.

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