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Use of proton pump inhibitors and risk of ischemic events in the general population

  • Manuela Casula
    Correspondence
    Corresponding author.
    Affiliations
    Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy
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  • Lorenza Scotti
    Affiliations
    Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy
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  • Federica Galimberti
    Affiliations
    Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy
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  • Francesco Mozzanica
    Affiliations
    Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy
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  • Elena Tragni
    Affiliations
    Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy
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  • Giovanni Corrao
    Affiliations
    Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy
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  • Alberico L. Catapano
    Affiliations
    Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy

    IRCCS MultiMedica, Via Milanese 300, 20099, Sesto S. Giovanni (MI), Italy
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      Highlights

      • Efficacy and good tolerability profile of PPIs can lead to overutilization.
      • Little is known about potential cardiovascular adverse effects of PPIs.
      • PPI use is associated with an increased risk of hospitalization for CV events.
      • The increased risk was observed even in patients not treated with antithrombotics.
      • PPI use should be critically considered, especially when is not strictly necessary.

      Abstract

      Background and aims

      A potential increased risk of cardiovascular events has been suggested for proton pump inhibitors (PPIs), the most commonly prescribed drugs for the management of upper gastrointestinal disorders. We aimed to estimate the risk of hospitalization for cardio/cerebrovascular (CV) events in a cohort of incident PPI users.

      Methods

      A nested case-control study was carried out using regional healthcare utilization databases. For each case (hospitalization for non-haemorrhagic CV event), up-to-five controls randomly selected from the cohort were matched by gender, age at cohort entry, and index date. Exposure was estimated as recency of therapy (current, recent and past users) and number of days covered. Adjusted conditional logistic regression was used to estimate the association between exposure and outcome.

      Results

      Among new PPI users, we identified 17,832 cases and 89,160 controls (males 64.9%; mean age 58.9 years). Cases showed a significantly higher prevalence of use of drugs for diabetes, hypertension and hypercholesterolemia than controls. Risk of CV events was significantly higher for current (OR 1.61; 95%CI 1.55–1.68) and recent users (OR 1.15; 95%CI 1.06–1.26) compared to past users. Analogous results were found stratifying for cardiovascular (ORcurrent 1.71; 95%CI 1.63–1.81) and cerebrovascular events (ORcurrent 1.43; 95%CI 1.34–1.54). The increased risk was confirmed in subgroups by antithrombotic, statin use, or exposure duration. The same analysis for H2-antagonists use showed no significant results.

      Conclusions

      In primary care setting, PPI use was independently associated with increased risk of first-time cardiovascular event, consistent with the evidence that PPIs adversely impact vascular function, underlying the need to promote appropriate prescribing of these drugs.

      Keywords

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