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Comment & Response |

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

Arief Lalmohamed, PharmD1; Niels Vermeer, PharmD2; Frank de Vries, PharmD, PhD3
[+] Author Affiliations
1Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands
2Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
3Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, the Netherlands
JAMA Intern Med. 2013;173(16):1559. doi:10.1001/jamainternmed.2013.8468.
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To the Editor Maggio and colleagues demonstrated a 51% increased 1-year mortality with the use of proton pump inhibitors (PPIs) in elderly patients discharged from acute care hospitals.1 However, a meta-analysis of 20 randomized clinical trials did not show a difference in all-cause mortality (odds ratio, 1.01; 95% CI, 0.74-1.40) between the use of PPIs (n = 2020) and the use of placebo or histamine 2 receptor antagonists (n = 2062).2 Observational studies show harmful effects of PPIs on various health outcomes surprisingly often, whereas randomized clinical trials do not. For example, observational studies showed a 34% increased risk of major adverse cardiac events following PPI use vs nonuse,3 which was not confirmed in randomized clinical trials (rate ratio, 0.99; 95% CI, 0.68-1.44) (median age of 69 years).4 The discrepancy between randomized trials and observational studies may be explained by residual confounding in epidemiological studies. Individuals taking PPIs often have a higher disease burden, which is not fully accounted for. Additional examples include an excessive alcohol intake, a sedentary lifestyle, and the use of systemic corticosteroids,5 which was not adjusted for in the observational study by Maggio and coworkers.1


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September 9, 2013
Marcello Maggio, MD, PhD; Andrea Corsonello, MD
1Section of Geriatrics, Department of Clinical and Experimental Medicine, University Hospital of Parma, Parma, Italy2Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy
3Unit of Geriatric Pharmacoepidemiology, Italian National Research Centres on Aging (INRCA), Cosenza, Italy
JAMA Intern Med. 2013;173(16):1559-1560. doi:10.1001/jamainternmed.2013.8459.
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