Spechler SJ, Hunter JG, Jones KM, et al. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019 Oct 17;381(16):1513-1523. doi: 10.1056/NEJMoa1811424. (Original study)

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).

METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive 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 Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year.

RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. 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 = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17).

CONCLUSIONS: 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. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Discipline Area Score
Internal Medicine 7 / 7
Gastroenterology 7 / 7
Surgery - Gastrointestinal 7 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Comments from MORE raters

Gastroenterology rater

Useful information for a common scenario in GI practice. Important that only a minority of patients were eligible, and that surgery was effective after careful patient selection.

Gastroenterology rater

All practitioners should be aware of this pivotal article. I reviewed it last week and forwarded this to our GI faculty and fellows. One of the most important points here is that only highly selected patients benefit from surgery, which requires a thorough multi-disciplinary evaluation.

General Internal Medicine-Primary Care(US) rater

The findings from the pre-randomization procedures are very interesting, excluding 288 of 366 patients for alternative diagnoses (44%), not completing the workup (19%), or other reasons (15%). Careful and methodical selection of patients for consideration for surgical treatment appears prudent.

General Internal Medicine-Primary Care(US) rater

This VA-based study of refractory heartburn showed that 80% of patients studied with esophageal biopsy and manometry did not have acid-related symptoms and only 20% had symptoms caused by reflux. Of those with reflux, surgery helped more than intensive medical treatment with both baclofen for GE symphicer and desiprimine for symptom control.

General Internal Medicine-Primary Care(US) rater

Well designed trial. The tricky conclusion might be that surgery helps in select cases that clearly have GERD that can make it through a rigorous prior evaluation. Only a sixth of cases made it to randomization. The trial also highlights how other things other than GERD can be found by a thorough evaluation. Although surgery works, the trial also shows that thorough evaluation also identifies a lot of people who would not benefit from surgery.

Internal Medicine rater

Useful in deciding treatment for this common problem.

Surgery - Gastrointestinal rater

Useful article with clear results.
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