Dallas, TX—For most patients visiting their doctor’s office complaining of heartburn and other gastrointestinal-reflux issues, proton-pump inhibitors (PPIs) are the first-line treatment. But what happens next when those drugs provide inadequate relief in 30% or more of the users?

An article in the New England Journal of Medicine discussed a potentially practice-changing study conducted at U.S. veterans’ hospitals to provide guidance on when surgery might be the best option. The report also decries the limited nonsurgical options when PPIs don’t work.

“Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes,” write the authors, led by researchers from Baylor University Medical Center and the Veterans’ Affairs North Texas Healthcare System.

“Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or anti-reflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).”

Which treatment is optimal in what cases has far-reaching effect on medical practice, based on the sheer volume of patients with gastroesophageal reflux disorder (GERD). Background in the article points out that, in the U.S. about one in five adults regularly has gastrointestinal-reflux symptoms, and that annual costs for managing GERD top $12 billion.

Although PPIs are useful for healing reflux esophagitis, according to the report, they tend to be less effective for eliminating GERD symptoms, which persist in about 30% of patients taking the drugs.

In fact, only 58% of patients taking prescription PPIs for chronic heartburn report complete satisfaction with their treatment. The result is that “PPI-refractory GERD” is the most common reason for gastroenterologist referrals, according to the article.

To help determine the best approach, the study team focused on 366 patients referred to VA gastroenterology clinics for PPI-refractory heartburn. Those veterans, mean age 48.5 years and a majority of whom were men, received 20 mg of omeprazole twice daily for 2 weeks. If heartburn persisted, gastroenterologists then introduced endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring.

With 78 patients remaining after exclusions, the study team determined that the incidence of treatment success with surgery (18 of 27 patients, 67%) was “significantly superior” to that with active medical treatment (7 of 25 patients, 28%; P = .007) or control medical treatment (3 of 26 patients, 12%; P <.001).

“Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients,” the authors concluded. “For that highly selected subgroup, surgery was superior to medical treatment.”

The results come with a strong caution, however. Fundoplication, antireflux surgery, creates a barrier to reflux of all gastric material—acidic and nonacidic—and, therefore, should relieve PPI-refractory heartburn that is reflux-related, according to the study.

“In practice, however, patients with ‘GERD symptoms’ that are unresponsive to PPIs often do not have a response to surgery either,” the authors caution. “This might result from preoperative failure to document that the symptoms are truly reflux-related. Alternatively, for patients with reflux hypersensitivity, surgical reduction of reflux might not relieve symptoms generated by a hypersensitive esophagus.”

The authors called for systematic evaluation of patients before scheduling them for surgery to increase success rates.

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