Strategy Reduces Inappropriate Proton Pump Inhibitor Use

A dual deprescribing intervention for proton pump inhibitors (PPIs) targeting patients and their primary care doctors proved effective in reducing potentially inappropriate use, a cluster-randomized trial in France found.

At 1 year, the combined approach — where patients got educational material about reducing PPI use mailed to them and their physicians received a letter detailing a deprescribing algorithm — resulted in twice as many patients cutting their PPI use in half (14.9%) versus usual care (7%) or physician-targeted intervention alone (7.7%, P<0.001 for both).

The results underscore “the value of prioritizing patient-facing deprescribing strategies,” wrote researchers led by Jean-Pascal Fournier, MD, PhD, of Nantes Université in France, in JAMA Internal Medicine. Furthermore, the interventions were not associated with a resurgence in gastroesophageal reflux disease (GERD) symptoms.

PPIs in the U.S. are frequently prescribed for inappropriate indications and sometimes prescribed indefinitely, according to Fournier and colleagues.

“Inappropriate use is associated with an increased risk of kidney adverse events (acute interstitial nephritis and chronic kidney disease), multidrug-resistant microorganisms intestinal colonization, Clostridium difficile infection, pneumonia, bone fractures, dementia, and cardiovascular events,” the researchers noted. “In addition, two recent studies have suggested an increased risk between long-term PPI use and colorectal cancer and even all-cause mortality compared with histamine-2 receptor antagonists.”

Potentially unnecessary PPI spending — reimbursements in 2015 hit $12 billion in the U.S., for example — offer another motivation for deprescribing.

An important limitation of the current study was the effect of patient-education alone was not studied, according to Timothy S. Anderson, MD, MAS, of the University of Pittsburgh.

“The observed three-group comparisons provide a suggestion, but cannot confirm, that a patient-only intervention may be efficacious and provide an efficient mechanism for catalyzing deprescribing conversations,” he wrote in an editorial accompanying the study. “While this patient-only strategy may be more feasible for large health systems, the opportunity to engage clinicians as well as patients poses many advantages for deprescribing interventions which can be challenging to implement.”

Anderson noted that “clinical practice guidelines are increasingly acknowledging the need to incorporate deprescribing as a core component of high-quality prescribing, particularly for legacy drugs like PPIs, demonstrating the imperative for future clinical trials focused on implementing evidence-based deprescribing practices into clinical practice.”

While this study is a good start, he added, “PPI deprescribing remained infrequent in all study groups, pointing toward the need for both more effective implementation strategies as well as the need for future clinical trials for legacy drugs that examine the benefits and the risks of deprescribing.”

DEPRESCRIPP (Efficacy of a Multifaceted Intervention to Deprescribe Proton Pump Inhibitors [PPI] in Primary Care: A Population-based, Pragmatic, Cluster-Randomized Controlled Trial) was conducted in two regions of western France from November 2020 to November 2021. The 34,409 patients included were adults with at least 1 year of PPI use and their 1,498 general practitioners across 683 primary care practices.

Randomization included three groups: the patient- and physician-facing intervention together, the physician-oriented intervention alone, or usual care (no intervention).

The patient intervention involved mailing a 4-page educational brochure that asked patients to consider whether they should still be taking PPIs, with information on their indications for use and potential risks and alternatives.

The physician-oriented intervention involved sending a PPI deprescribing algorithm that included recommendations for lowering the PPI dosage or stopping in certain cases (mild or moderate esophagitis, treated GERD, stress ulcer prophylaxis after intensive care) along with follow-up protocols. The algorithm recommended continued use for patients with severe esophagitis, those with a documented history of bleeding gastrointestinal (GI) ulcers, and chronic users of nonsteroidal anti-inflammatory drugs who have a bleeding risk.

The mean patient age was about 69 years, and 57% were women. Mean baseline annual PPI use was 413.7 defined daily doses. Esomeprazole (Nexium) was the most commonly prescribed PPI (45%), followed by omeprazole (Prilosec; 27%), pantoprazole (Protonix; 18%), and others.

Fournier and co-authors noted that a subgroup analysis of the primary outcome failed to identify “meaningful” patient- or physician-level factors for more targeted interventions.

In a sample of 1,532 patients who responded to a questionnaire about GERD symptoms at 1 year, mean GERD Impact Scale scores did not significantly differ between either the dual intervention or physician-facing groups and the usual care group:

• Upper GI symptoms: 3.23 and 3.28 vs 3.27, respectively
• Other acid-related GI symptoms: 3.09 and 3.13 vs 3.13
• Impact of symptoms on daily activities: 3.27 and 3.28 vs 3.27

Study limitations included the open-label design and that patients identified for deprescribing were found via the National Health Insurance database, which may have inadvertently targeted appropriate PPI users for deprescribing. The database also cannot capture inappropriate use of over-the-counter PPIs.

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