Many patients with ‘refractory’ heartburn successfully treated with PPI regimen

Among study participants whose reflux-related heartburn truly did not respond to a proton-pump inhibitor (PPI), surgery (laparoscopic Nissen fundoplication) was more effective than medical therapy (omeprazole and baclofen plus desipramine if needed).

A study of patients referred for apparently refractory heartburn found that many could achieve relief on a proton-pump inhibitor (PPI) and that for those found to have refractory reflux-related heartburn, surgery was more effective than medical therapy.

The trial included 366 patients referred to Veterans Affairs gastroenterology clinics for PPI-refractory heartburn. To start, all received 20 mg of omeprazole twice daily for two weeks, which provided relief to 42 patients. Remaining patients underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance (MII)–pH monitoring. This revealed that 23 patients had esophageal disorders other than gastroesophageal reflux disease (GERD) and that 99 had functional heartburn. An additional 70 patients did not complete trial procedures, and 54 were excluded for other reasons.

The remaining 78 patients were randomly assigned to surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the GERD–Health Related Quality of Life score. Success was significantly more common with surgery (18 of 27 patients, 67%) than active medical treatment (7 of 25 patients, 28%; P=0.007) or control treatment (3 of 26 patients, 12%; P<0.001). The active medical treatment group had a higher rate of success than the control group, but the difference was not statistically significant (16 percentage points; 95% CI, −5 to 38; P=0.17). Results were published in the Oct. 17 New England Journal of Medicine.

The study shows that surgery was superior to medical treatment for patients with “truly PPI-refractory and reflux-related heartburn,” but the study found this condition in only a minority of referred patients, the authors said. They offered two explanations for why twice-daily omeprazole may have been effective for so many: Patients were explicitly instructed to take it 30 minutes before meals, and different PPIs vary in their potency and their effectiveness for individual patients. Limitations of the study include the small sample size and the mostly white male veteran patient population.

“We conclude that systematic workup including esophageal MII-pH monitoring can identify a subgroup of patients with PPI-refractory heartburn, including those with reflux hypersensitivity, who can have a response to antireflux surgery,” the authors wrote. They cautioned, however, that even in this selected subgroup, surgery worked for only two out of three patients, a statistic that should be shared with those considering treatment options.

An accompanying editorial additionally warned that the surgery carries risks of morbidity and mortality and the possibility exists that surgical success in the study was due to placebo response. The editorialist wrote that although the results of the surgical intervention were striking, “the findings should not translate into more patients with refractory heartburn being offered surgery without each case being judiciously evaluated on its merits, and only after extended trials of medical therapy.”