Late Breaking News
VA's Overuse of GERD Treatment Under Scrutiny
By Brenda L. Mooney
CHICAGO - How VA patients are treated, -- or potentially overtreated, --- for gastroesophageal reflux disease (GERD) is coming under greater scrutiny.
Veterans often are prescribed proton pump inhibitors (PPI) at much higher doses than recommended, then kept on the drugs far too long, according to the VA-funded study released this year.1
While that study looked at PPI prescriptions in patients newly diagnosed with GERD and followed them for two years, other VA studies during the past few years have focused on the appropriateness of PPI use in ambulatory care clinics and the high cost of nonformulary PPIs.
For the recent study, funded by VA and published in the Journal of General Internal Medicine, researchers evaluated more than 1,600 veterans at the Edward Hines, Jr. VAMC from 2003 to 2009 and found the majority of patients received more than a three-month initial supply of medication, that nearly 25% of patients were given high total daily dose prescriptions and that very few patients who started on high-dose therapy had reductions in dosing more than two years after their initial prescription.
“We should always have a reevaluation after an initial prescription and ask, ‘Does this patient need to be on this medication?’” said Andrew Gawron, MD, first author of the study and a fellow in the division of gastroenterology and the Center for Healthcare Studies at Northwestern University Feinberg School of Medicine in Chicago. “Proton pump inhibitors are provided ubiquitously in medicine, and although they provide relief for many patients, optimal prescribing is important to avoid prolonged, unnecessary use and cost.”
Of the 1,621 patients included in the study, 378 (23.3%) had high total daily dose initial PPI prescriptions, and 1,243 (76.7%) patients had standard total daily dose initial prescriptions, according to the report.
Most patients (65.8%) received a 90-day or greater initial prescription. Over the two years following the initial PPI prescription, 13.0% of patients with initial standard daily dose prescriptions had evidence of step-up therapy, while only 7.1 % of patients with initial high daily dose PPI prescriptions had evidence of step-down therapy.
The study also pointed out that 83.8% of veterans had at least one refill over two years, and the overall medication possession ratio was 0.86.
A brief communication published last year in the Journal of Managed Care Pharmacy quantified the widespread prescribing of PPIs at the VA.
“Of 58,605 unique patients seen in this VA health care system in the 12-month period from July 1, 2008, through June 30, 2009, 13,713 (23.4%) received a PPI, and of these, 10,483 (76.4%) received at least 120 PPI units and were defined as long-term users.”2
Both the American Board of Internal Medicine and the American Gastroenterology Association recommend that PPIs be prescribed at the lowest effective dose for four to eight weeks to treat GERD. If symptoms persist after eight weeks, according to those groups, other potential causes of symptoms and alternative approaches to therapy should be pursued.
“It seems that, once these veterans are prescribed a PPI, they are rarely taken off of it,” Gawron said about his research. “Two years after their initial prescription, most are still on the drug.”
The pharmacy article noted that one-year PPI use prevalence was 23% among the VA population in the study period from mid-2008 to mid-2009 and that long-term use prevalence was 18%. Complicating the issue was that nonformulary PPI use accounted for 10.5% of the prescribed units and 9.7% of the users, while 57.3% of total PPI drug cost, the authors said. They added that, while a pharmacy consult is required to permit non-formulary PPI use, there is no clear VA guideline for what constitutes therapeutic failure or intolerance.
A 2010 study of patients at a VA clinic in Ann Arbor, MI, meanwhile, found that many patients probably never should have taken PPIs in the first place.3
Of 946 patients in an ambulatory care setting evaluated in that research, 35.4% were given PPI therapy for an appropriately documented upper gastrointestinal tract diagnosis, 10.1% received PPIs empirically for symptomatic treatment based on extra-esophageal symptoms, 18.4% received PPIs for gastro-protection, and 36.1% had no documented appropriate indication for PPI therapy.
Lead author Joel J. Heidelbaugh, MD , of the Department of Family Medicine at the University of Michigan in Ann Arbor and his colleagues noted in the study that a subgroup analysis found that 48.6% of patients across all four categories received PPIs without documentation of re-evaluation of upper gastrointestinal tract symptoms, accounting for 1,034 patient-years of PPI use. The study, which was published in the American Journal of Managed Care, estimated that total cost of inappropriate PPI use was $233,994 based on over-the-counter PPI costs and $1,566,252 based on average wholesale price costs.
“Proton pump inhibitors are often overused in the ambulatory care setting without documented valid indications,” the authors wrote. “Inappropriate use of PPIs is associated with substantial cost expenditure and with the potential for adverse events.”
In fact, researchers in the 2010 study noted that potentially related adverse events in this cohort included six cases of Clostridium difficile-associated diarrhea (CDAD) and one case of community-acquired pneumonia (CAP).
In February, the Food and Drug Administration issued a safety announcement, cautioning that proton pump inhibitors could be associated with an increased risk of CDAD and suggesting that healthcare providers consider a diagnosis of CDAD when patients taking PPIs develop diarrhea that does not improve.
Previous FDA communications discussed the risks of low magnesium levels and higher rates of bone fractures with PPI use.
A study out of the New England VA Healthcare System, published last year in Clinical Infectious Diseases, found that among 1,544 veterans studied, “current compared with past PPI exposures associated modestly with increased risks of CAP.”4
In terms of the range of the benefits-risks calculation, a report in the journal American Family Physician last year said that, while PPIs “effectively treat gastroesophageal reflux disease, erosive esophagitis, duodenal ulcers and pathologic hypersecretory conditions” and “cause few adverse effects with short-term use,” longer-term use can be problematic.5
Extending therapy with the drugs “has been scrutinized for appropriateness, drug-drug interactions and the potential for adverse effects (e.g., hip fractures, cardiac events, iron deficiency, Clostridium difficile infection, pneumonia). Adults 65 years and older are more vulnerable to these adverse effects because of the higher prevalence of chronic diseases in this population,” according to the article.
Heidelbaugh also was the lead author of a report earlier this year that discussed why PPIs often are overused.
Nothing that PPIs “remain the leading evidence-based therapy for upper gastrointestinal disorders, including gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease,” the article in Therapeutic Advances in Gastroenterology added, “The overutilization of PPIs in ambulatory care settings is often a result of failure to re-evaluate the need for continuation of therapy, or insufficient use of on-demand and step-down therapy.”6
While clinicians might be concerned whether discontinuing PPI therapy will lead to rebound hypersecretion of gastric acid and ultimately, hypergastrinemia, the article suggested that “conflicting” data made it far from an established outcome.
The recent Northwestern University study, meanwhile, suggests that tracking treatment patterns at the VA will help solve the problems of overuse and inadequate monitoring.
“These results provide detailed data on prescribing and use of PPIs to help guide efforts for optimal PPI use in U.S. veterans,” the authors concluded.
1. Gawron AJ, Pandolfino JE, Miskevics S, Lavela SL. Proton Pump Inhibitor Prescriptions and Subsequent Use in US Veterans Diagnosed with Gastroesophageal Reflux Disease. J Gen Intern Med. 2013 Feb 12. [Epub ahead of print] PubMed PMID: 23400526.
2. Ajumobi AB, Vuong R, Ahaneku H. Analysis of nonformulary use of PPIs and excess drug cost in a Veterans Affairs population. J Manag Care Pharm. 2012 Jan-Feb;18(1):63-7. PubMed PMID: 22235956.
3. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010 Sep;16(9):e228-34. PubMed PMID: 21250399.
4. Hermos JA, Young MM, Fonda JR, Gagnon DR, Fiore LD, Lawler EV. Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed. Clin Infect Dis. 2012 Jan 1;54(1):33-42. doi: 10.1093/cid/cir767. Epub 2011 Nov 18.
5. Ament PW, Dicola DB, James ME. Reducing adverse effects of proton pump inhibitors. Am Fam Physician. 2012 Jul 1;86(1):66-70. Review. PubMed PMID: 22962914.
6. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012 Jul;5(4):219-32. doi: 10.1177/1756283X12437358. PubMed PMID: 22778788; PubMed Central PMCID: PMC3388523.