Harmful Effects of Proton Pump Inhibitors: Discrepancies Between Observational Studies and Randomized Clinical Trials—Reply

Maggio, Marcello; Corsonello, Andrea

doi:10.1001/jamainternmed.2013.8459

Cited by 2 publications

(1 citation statement)

References 4 publications

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“…[ 10 ] In fact both studies included patients at a higher risk of MI than the general population, which may eclipse any potential harm conferred by PPIs due to competing risks. [ 38 , 39 ] Based on the concern that PPIs could reduce the metabolism of clopidogrel to its active form, the FDA issued a warning about this possible drug-drug interaction in 2009 [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

et al. 2015

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Background and AimsProton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.MethodsUsing a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.ResultsIn multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.ConclusionsConsistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

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Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

et al. 2015

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Continuous Proton Pump Inhibitor Therapy and the Associated Risk of RecurrentClostridium difficileInfection

et al. 2015

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IMPORTANCE Clostridium difficile infection (CDI) is associated with significant morbidity, mortality, and a high risk of recurrence. Proton pump inhibitor (PPI) use is associated with an initial episode of CDI, and PPIs are frequently overprescribed. For many, the use of PPIs could likely be discontinued before CDI recurrence. OBJECTIVES To determine whether PPI use was associated with a risk of initial CDI recurrence, to assess what proportion of patients who developed CDI were taking a PPI for a non-evidence-based indication, and to evaluate whether physicians discontinued unnecessary PPIs in the context of CDI. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study of incident health care-associated CDI cases to determine the association between continuous PPI use and CDI recurrence within 90 days. The setting was 2 university-affiliated hospitals, the 417-bed Montreal General Hospital (Montreal, Quebec, Canada) and the 517-bed Royal Victoria Hospital (Montreal, Quebec, Canada). The cohort consisted of 754 patients who developed health care-associated CDI between January 1, 2010, and January 30, 2013, and who survived for a minimum of 15 days after their initial episode of nosocomial CDI. EXPOSURE Continuous PPI use. MAIN OUTCOMES AND MEASURES Recurrence of CDI within 15 to 90 days of the initial episode. RESULTS Using a multivariable Cox proportional hazards model, the cause-specific hazard ratios for recurrence were 1.5 (95% CI, 1.1-2.0) for age older than 75 years, 1.5 (95% CI, 1.1-2.0) for continuous PPI use, 1.003 (95% CI, 1.002-1.004) per day for length of stay, and 1.3 (95% CI, 0.9-1.7) for antibiotic reexposure. The use of PPIs was common (60.7%), with only 47.1% of patients having an evidence-based indication. Proton pump inhibitors were discontinued in only 3 patients with CDI. CONCLUSIONS AND RELEVANCE After adjustment for other independent predictors of recurrence, patients with continuous PPI use remained at elevated risk of CDI recurrence. We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.

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Harmful Effects of Proton Pump Inhibitors: Discrepancies Between Observational Studies and Randomized Clinical Trials—Reply

Cited by 2 publications

References 4 publications

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

Continuous Proton Pump Inhibitor Therapy and the Associated Risk of RecurrentClostridium difficileInfection

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