Surgery Best Option in the Uncommon Case When PPIs Fail to Stem Heartburn

By Gene Emery

October 17, 2019

NEW YORK (Reuters Health) - When heartburn is refractory to proton-pump inhibitor (PPI) treatment, antireflux surgery is a better option than reflux-reducing medication such as baclofen or treatment with neuromodulators, a new clinical trial shows.

But the study, conducted at Veterans Affairs gastroenterology clinics, also found through extensive workups that true PPI-refractory and reflux-related heartburn was only present in about a third of the volunteers thought to have the condition.

Out of 366 potential candidates for the trial, 42 were excluded because two weeks of omeprazole therapy at 20 mg twice daily solved the problem, 23 had non-gastroesophageal reflux disease (non-GERD), and 88 had functional heartburn not due to GERD or had some other type of histopathologic, motility or structural abnormality.

Another 70 people were excluded for not completing all the testing and 54 were not randomized for other reasons such as morbid obesity or having a coexisting condition.

Of the 78 patients randomized in the study and assessed after one year, surgery without any heartburn medications worked in 67%, researchers report Wednesday online in The New England Journal of Medicine.

Active medical treatment that added baclofen and desipramine to omeprazole worked in 28% (P=0.007 favoring surgery), and omeprazole plus placebo was effective in just 12% (P<0.001 favoring surgery).

The surgery consisted of laparoscopic Nissen fundoplication, which involves wrapping the upper part of the stomach around the lower end of the esophagus.

"This study shows that in many of these patients it's a plumbing problem," chief author Dr. Stuart Jon Spechler of Baylor University Medical Center, in Dallas, told Reuters Health by phone.

"The proton-pump inhibitors stop acid production but they don't do anything to correct the underlying reflux problem caused by a valve that is not working, and that's what you can repair with an operation," he said.

But "it's really important to do a very extensive workup to make sure these patients who have heartburn that doesn't respond to PPIs really have GERD as the cause of the heartburn, because most of them did not," said Dr. Spechler.

Heartburn is a key symptom of gastroesophageal reflux disease, which affects an estimated 20% of Americans. The proton-pump inhibitors, which have become the mainstay of therapy, do not work well in about 30% of patients and 42% of people who take them are not completely satisfied with their effectiveness.

Treatment is complicated because several factors can cause the problem and there is not a lot of good data on the best strategy. For example, many patients classified as having reflux disease who are not helped by the drugs aren't helped by surgery either.

Treatment was considered successful if there was an improvement of at least 50% in the patient's GERD-HRQL score, which measures quality of life on a 51-point scale.

Surgery was 2.38 times more successful than active medical treatment and 5.78 times more successful than omeprazole plus placebo.

"The incidence of success in the surgery group was 71% among the 14 patients with reflux hypersensitivity and 62% among the 13 with abnormal acid reflux," the researchers reported.

The rates of serious adverse events were comparable in the three groups. One patient in the surgery group required a second operation.

Of the 11 patients who had one or more serious adverse events, the only event that occurred more than once was hospitalization for suicidal ideation, which happened in one patient who was in the placebo group and one patient in the surgery group who was not given omeprazole.

But most patients never got into the study.

"I was surprised how infrequent GERD was in this population," said Dr. Spechler.

The team said a sizable minority of candidates for the study probably got relief from omeprazole because they received explicit instructions to take it 30 minutes before breakfast and dinner.

"A lot of people don't take proton-pump inhibitors correctly," the researcher said.

The screening process also included endoscopy, esophageal biopsy, esophageal manometry and multichannel intraluminal impedance-pH monitoring.

"Anybody who's bothered enough by heartburn that persists despite PPI, before considering any type of invasive treatment, they really do need this type of workup," said Dr. Spechler. "All these tests are available at virtually all gastroenterology offices around the country. Certainly before having an operation you'd be very wise to go through this workup."


N Engl J Med 2019