Long-Term Safety of PPIs

Summary and Comment |
April 30, 2015

Long-Term Safety of PPIs

  1. David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Follow-up data show low rates of serious adverse events.

  1. David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Proton-pump inhibitors (PPIs) are often used for long periods of time because of chronic conditions or risks. The safety of such use remains unclear.

To evaluate the safety of chronic PPI use, investigators analyzed safety data from two industry-funded prospective trials randomizing patients with gastroesophageal reflux disease (GERD) to PPI (omeprazole or esomeprazole) therapy or antireflux surgery (ARS). In the SOPRAN study, serious adverse events (SAEs) were assessed in 298 patients with median exposures of 12 years in the PPI group and 10 years in the ARS group. The LOTUS study had a similar design and involved 514 patients with median exposures of 5 years in both groups. In each study, results were as follows:

  • The rate of SAEs was similar in the PPI group and the ARS group.

  • One femur fracture occurred in each group.

  • Bacterial gastroenteritis and pneumonia rates were similar between groups.

  • Laboratory values of biomarkers (including hematology, liver enzymes, electrolytes, vitamin D, and vitamin B12) showed no changes over time.

  • Gastrin and chromogranin A levels increased in the PPI group, mainly during the first year.

  • Incidence rates of neoplasms and cardiovascular events were similar between groups.


The investigators conclude that 5 to 12 years of continuous PPI therapy presents no major safety concerns. Among the host of potential side effects of PPIs previously suggested, concerns of gastric atrophy and neoplasia were not supported by study findings, but an elevated risk for femoral fractures was indicated in case-control studies, resulting in a prescribing warning in some countries. The current data from prospective, randomized trials of long-term PPI therapy suggest that SAEs are uncommon and occur at similar rates in those patients not taking PPIs. Nonetheless, individual risk factors for specific SAEs should be considered when prescribing long-term PPI therapy.

Editor Disclosures at Time of Publication

  • Disclosures for David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) at time of publication Leadership positions in professional societies World Gastroenterology Organization (Treasurer)


Reader Comments (4)

Monika Jacyszyn-Owczarek Other Healthcare Professional, Pharmacology/Pharmacy, Pharmaceutical Industry,

We need to check the data quality and reliability of such publications durig postauthorisathion period of medicinal products. Such publications are the basis for assessing the safety of medicinal products and taking or not certain pharmacovigilance activities.

Victor Kantariya Physician, Family Medicine/General Practice

Routine acid-suppresive therapy with PPIs may be harmul in critically ill patients with acute stroke (Ann Neurol 2014 Nov). Among 1876 patients with stroke PPI use was associated with significantly higher risk for pneumonia(odds ratio,2.7). PPI s might worsen pneumonia , especially aspiration and ventilator-associated pneumonias. Acid Suppressors and hospital pneumonia, that is the question. Victor Kantariya, MD

George Kent, MD Physician

Important study.

James Recht, MD Physician, Psychiatry, Community Mental Health Center

Here is how low we have sunk: two studies, both designed and paid for by the companies that profit from their sales, indicate that life-long use of PPI's is just fine -- and now, trusted experts approve. If this is not a case of fox guarding henhouse, then what is?

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