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Original article| Volume 96, ISSUE 10, P2540-2549, October 2021

Association of Proton Pump Inhibitors With Higher Risk of Cardiovascular Disease and Heart Failure



      To examine associations of cumulative exposure to proton pump inhibitors (PPIs) with total cardiovascular disease (CVD; composed of stroke, coronary heart disease, and heart failure [HF]) and HF alone in a cohort study of White and African American participants of the Atherosclerosis Risk in Communities (ARIC) study.


      Use of PPIs was assessed by pill bottle inspection at visit 1 (January 1, 1987 to 1989) and up to 10 additional times before baseline (visit 5; 2011 to 2013). We calculated cumulative exposure to PPIs as days of use from visit 1 to baseline. Participants (n=4346 free of total CVD at visit 5; mean age, 75 years) were observed for incident total CVD and HF events through December 31, 2016. We used Cox regression to measure associations of PPIs with total CVD and HF.


      After adjustment for potential confounding variables, participants with a cumulative exposure to PPIs of more than 5.1 years had a 2.02-fold higher risk of total CVD (95% CI, 1.50 to 2.72) and a 2.21-fold higher risk of HF (95% CI, 1.51 to 3.23) than nonusers.


      Long-term PPI use was associated with twice the risk of total CVD and HF compared with nonusers. Our findings are in concordance with other research and suggest another reason to be cautious of PPI overuse.

      Abbreviations and Acronyms:

      ARIC (Atherosclerosis Risk in Communities), CHD (coronary heart disease), CVD (cardiovascular disease), HF (heart failure), HR (hazard ratio), ICD (International Classification of Diseases), PPI (proton pump inhibitor)
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      Linked Article

      • The Cardiovascular Risk of Proton Pump Inhibitors and the Dangers of Polypharmacy
        Mayo Clinic ProceedingsVol. 96Issue 10
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          Proton pump inhibitors (PPIs) are among the most commonly prescribed medicines in the world and are used for a variety of indications, including peptic ulcer disease, gastroesophageal reflux disease, dyspepsia, and prevention of gastrointestinal bleed during antiplatelet therapy.1 A number of adverse effects, from Clostridium difficile infection2 to chronic kidney disease,3 have previously been observed with long-term use of PPIs. In addition, a link between long-term PPI use and increased cardiovascular risk has been suggested although not definitively established.
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