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<p>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&#xa0;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 <i>PPI</i>→<i>CKD</i>→<i>CVAE</i>, underscore the importance of monitoring renal function in long-term PPI users, and emphasise the need for future prospective trials to clarify cardiovascular risks.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月13日

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  • Kaile Chen,
  • Farhad Abtahi,
  • Carlos Fernandez-Llatas,
  • Hong Xu,
  • Fernando Seoane

摘要

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.