Surgery may be more effective than medical therapy, according to results from a randomized trial in 78 patients with reflux-related heartburn refractory to proton pump inhibitors (PPIs).
, from Baylor University Medical Center, Dallas, and coauthors wrote in the New England Journal of Medicine that, for these patients, there were no medical treatment options that had been shown to have long-term benefit, so PPIs were often continued despite not offering adequate symptom relief. Other medical options such as baclofen and neuromodulators often have unacceptable side effects, and studies of their efficacy were few and of short duration.
In this study, patients were randomized either to laparoscopic Nissen fundoplication, treatment with omeprazole plus baclofen with desipramine depending on symptoms, or a control treatment of omeprazole plus placebo.
At 1 year, researchers saw a significantly higher rate of treatment success – defined as 50% or greater improvement in gastroesophageal reflux disease health-related quality of life score – in the surgery group (67%), compared with the medical-treatment group (28%) and control-medical group (12%).
This translated to an unadjusted 138% greater chance of treatment success with surgery, compared with active medical treatment, and a greater than 400% increase for surgery, compared with the control medical treatment.
Researchers also did a prespecified subgroup analysis among people with reflex hypersensitivity or abnormal acid reflux, and found the incidence of success with surgery was 71% and 62%, respectively.
They described this finding as “noteworthy,” given that reflux hypersensitivity was considered a functional disorder that would not be expected to improve with a procedure that didn’t alter abnormal esophageal pain perception.
However, they acknowledged that, as the study did not include a sham-surgery group, they couldn’t determine how much the placebo effect might have contributed to the treatment success of surgery.
They also stressed that the randomized group was a highly selected group of patients, and that the systematic work-up including esophageal multichannel intraluminal impedance pH monitoring could identify a subgroup that might have a better response to surgery than to medical treatment.
Four patients in the surgery group experienced a total of five serious adverse events, including one patients who had a herniated fundoplication treated with repeat surgery; four patients in the active-medical group experienced four serious adverse events; and three patients in the control-medical group experienced five serious adverse events.
The authors noted that 366 patients with PPI-refractory heartburn were originally enrolled in the study, then treated with 20 mg of omeprazole twice daily for 2 weeks with strict instructions to take 20 minutes before breakfast and dinner. Of these patients, 42 had their symptoms relieved by the omeprazole treatment and so were excluded from the randomization.
The “strict instructions” on how to take omeprazole were important, because PPIs only bind to gastric proton pumps that are actively secreting acid, the authors wrote. They also commented that the relative potencies of individual PPIs can vary, so patients not on omeprazole before the study may have responded better to this than other PPIs.
Before randomizations, patients also underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance pH monitoring. This excluded another 23 patients who were found to have non–gastroesophageal reflux disease, including eosinophilic esophagitis, other endoscopic or histologic abnormalities, and manometric abnormalities.
“This trial highlights the critical importance of systematic evaluation, similar to that recommended by Gyawali and Fass for managing the care of patients with PPI-refractory heartburn,” they wrote. “Many patients would not complete this rigorous evaluation, and among those who did, the cause of heartburn in most of them was not [gastroesophageal reflux disease].”
The study was funded by the Department of Veterans Affairs Cooperative Studies Program. Four authors declared consultancies with and/or grants from the pharmaceutical sector.
SOURCE: Spechler SJ et al. N Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1811424.