# 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.

## Key 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.