Study Pinpoints Best Predictor of When Reflux Symptoms Don't Require PPI

Marcia Frellick

July 06, 2022

Four days is an optimal time for wireless reflux monitoring to determine which patients can stop taking proton pump inhibitors (PPIs) and which ones need long-term antireflux therapy, researchers report.

Dr Rena Yadlapati

"This first-of-its kind double-blinded clinical trial demonstrates the comparable, and in some cases better, performance of a simple assessment of daily acid exposure from multiple days of recording compared to other composite or complex assessments," write Rena Yadlapati, MD, with the Division of Gastroenterology at the University of California–San Diego, in La Jolla, and her co-authors.

Their findings were published online in the American Journal of Gastroenterology.

A substantial percentage of patients who have esophageal reflux symptoms do not have gastroesophageal reflux disease (GERD) and can stop taking PPIs.

Wireless reflux monitoring performed while patients are not taking PPIs is the gold standard for determining whether a patient has abnormal acid from GERD, but the optimal daily acid exposure time (AET) and the optimal duration of monitoring have not been well studied.

Aiming to fill this knowledge gap, Yadlapati and her colleagues conducted a single-arm, double-blinded clinical trial over 4 years at two tertiary care centers. They enrolled adult patients who had demonstrated an inadequate response to more than 8 weeks' treatment with PPIs.

Study participants were asked to stop taking their PPI for 3 weeks in order that the investigators could to determine the rate of relapse after PPI use and could establish the study reference standard to discontinue therapy. During the 3-week period, after having stopped taking PPIs for at least a week, patients underwent 96-hour wireless reflux monitoring. They were then told to continue not taking PPIs for an additional 2 weeks. They could use over-the-counter antacids for symptom relief.

The primary outcome was whether PPIs could be successfully discontinued or restarted within 3 weeks. Of the 132 patients, 30% were able to stop taking PPIs.

AET Less Than 4.0% Best Discontinuation Predictor

The team came to two key conclusions.

They found that acid exposure time of less than 4.0% was the best predictor of when stopping PPIs will be effective without worsening symptoms (odds ratio [OR], 2.9; 95% CI, 1.4 – 6.4). Comparatively, 45% (22 of 49 patients) with total AET of 4.0% or less discontinued taking PPIs, vs 22% (18 of 83 patients) with total AET of more than 4.0%.

Additionally, the investigators concluded that 96 hours of monitoring was better than 48 hours or fewer in predicting whether patients could stop taking PPIs (area under curve [AUC] for 96 hours, 0.63, vs AUC for 48 hours, 0.57).

Yadlapati told Medscape Medical News that the findings should be practice changing.

"You really need to test for 4 days," she said. She noted that the battery life of the monitor is 96 hours, and clinicians commonly only test for 2 days.

With only 1–2 days of monitoring, there is too much variability in how much acid is in the esophagus from one day to another. Monitoring over a 4-day period gives a clearer picture of acid exposure burden, she said.

Her advice: "If you have a patient with heartburn or chest pain and you think it might be from reflux and they're not responding to a trial of PPI, get the reflux monitoring. Don't wait."

After 4 days of monitoring, if exposure to acid is low, "they should really be taken off their PPI therapy," she said.

They likely have a condition that requires a different therapy, she added.

"It is very consistent with what we have thought to be the case and what some lower-quality studies have shown," she said. "It just hadn't been done in a clinical trial with a large patient population and with a full outcome."

PPI Often Used Inappropriately

Interest is high both in discontinuing PPI in light of widespread and often inappropriate use and in not starting treatment with PPIs for patients who need a different therapy.

As Medscape Medical News has reported, some studies have linked long-term PPI use with intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, vitamin deficiencies, heart attacks, strokes, dementia, and early death.

Dr Avin Aggarwal

Avin Aggarwal, MD, a gastroenterologist and medical director of Banner Health's South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson, told Medscape Medical News that this study provides the evidence needed to push for practice change.

He said his center has been using 48-hour reflux monitoring. He said anecdotally, they had gotten better data with 4-day monitoring, but evidence was not directly tied to a measurable outcome such as this study provides.

With 4-day monitoring, "we get way more symptoms on the recorder to actually correlate them with reflux or not," he said.

He said he will now push for the 96-hour monitoring in his clinic.

He added that part of the problem is in assuming patients have GERD and initiating PPIs in the first place without a specific diagnosis of acid reflux.

Patients, he said, are often aware of the long-term side effects of PPIs and are approaching their physicians to see whether they can discontinue them.

The data from this study, he said, will help guide physicians on when it is appropriate to discontinue treatment.

Yadlapati is a consultant for Medtronic, Phathom Pharmaceuticals, and StatLinkMD and receives research support from Ironwood Pharmaceuticals. She is on the advisory board with stock options for RJS Mediagnostix. Other study coauthors report ties to Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles, Johnson & Johnson, Reckitt, Phathom Pharmaceuticals, Daewood, Takeda, and Crospon. Study co-author Vaezi holds a patent on mucosal integrity by Vanderbilt. Aggarwal reports no relevant financial relationships.

Am J Gastroenterol. Published online June 10, 2022. Abstract

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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