Am Fam Physician. 2012 Oct 15;86(8):723-727.
Original Article: Reducing Adverse Effects of Proton Pump Inhibitors
Issue Date: July 1, 2012
Available at: http://www.aafp.org/afp/2012/0701/p66.html
to the editor: I found this review of proton pump inhibitors (PPIs) to be complete and well written. However, the reported risks of hip fractures associated with PPI use and of cardiac events when PPIs are used in combination with clopidogrel (Plavix) were overstated.
Although case-control studies based on administrative data showed an increased odds ratio for PPI use in persons who sustained hip fractures, this association did not hold for persons without other preexisting fracture risk factors.1 Prospective cohort studies have not shown an increased hip fracture risk in PPI users. PPI use does not appear to be associated with reduced bone density, which calls into question the hypothetical mechanism of reduced calcium absorption. Any association between PPI use and hip fractures might be explained by other risk factors in patients who tend to require PPIs, such as those who smoke.
As for the suggested increased risk of cardiac events in persons taking clopidogrel and PPIs, more recent cohort studies, a recent randomized controlled trial, and meta-analyses of the highest quality studies have not shown any association.2 Therefore, I would be reluctant to withhold PPIs from patients who might benefit from them based on undue concerns about unsubstantiated risks.
1. U.S. Food and Drug Administration. FDA Drug Safety Communication: possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed June 29, 2012.
2. Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors—where do we stand in 2012? World J Gastroenterol. 2012;18(18):2161–2171.
in reply: We appreciate the detailed analysis and comments by Dr. Konrad. The goal of our article was to make readers aware of potential adverse effects of long-term PPI use. Clinical data suggest that long-term use needs to be scrutinized, especially in older patients.
Dr. Konrad's reference from the U.S. Food and Drug Administration (FDA) states that over-the-counter (OTC) PPIs “are only intended for a 14 day course of treatment up to 3 times per year. … Healthcare professionals should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of . time than in the OTC PPI label.”1
As we stated, the clinical significance of interactions between PPIs and clopidogrel is unknown. However, retrospective analysis has shown an increased risk of rehospitalization and adverse coronary events with concomitant use of PPIs and clopidogrel. Also, the FDA required a change to the prescribing information for clopidogrel to reflect the increased risk.2 We agree that patients taking clopidogrel who would clearly benefit from PPI use should be prescribed a PPI. However, selecting a PPI other than omeprazole (Prilosec), administering the PPI at a different time than clopidogrel, or substituting a high-dose histamine H2 antagonist may be preferred.
1. U.S. Food and Drug Administration. FDA Drug Safety Communication: possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed July 24, 2012.
2. Plavix (clopidogrel) [product information]. Bridgewater, N.J.: Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; 2009
Send letters to Kenneth W. Lin, MD, MPH, Associate Deputy Editor for AFP Online, e-mail: email@example.com, or 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2680.
Please include your complete address, e-mail address, and telephone number. Letters should be fewer than 400 words and limited to six references, one table or figure, and three authors.
Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter will be construed as granting the American Academy of Family Physicians permission to publish the letter in any of its publications in any form. The editors may edit letters to meet style and space requirements.
Copyright © 2012 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact firstname.lastname@example.org for copyright questions and/or permission requests.
Want to use this article elsewhere? Get Permissions