https://gastroenterology.acponline.org/archives/2020/03/27/12.htm

In reflux-related heartburn unresponsive to PPIs, surgery increased treatment success vs active medical treatment

An ACP Journal Club commentary noted that physicians should not change their practice based on the results of the trial, which are in contrast to the literature and expert opinion, until they are confirmed by studies assessing objective primary end points.


A randomized trial of patients referred for apparently refractory heartburn found that many could achieve relief on a proton-pump inhibitor (PPI); however, for those with truly refractory reflux-related heartburn, surgery (laparoscopic Nissen fundoplication [LNF]) was more effective than medical therapy.

The study was published in the Oct. 17, 2019, New England Journal of Medicine and was summarized in the Oct. 25, 2019, ACP Gastroenterology Monthly. The following commentary, by Vivek Kumbhari, MBChB, and Lawrence J. Cheskin, MD, FACP, appeared in the ACP Journal Club section of the March 17 Annals of Internal Medicine.

The trial by Spechler and colleagues suggests that, at least in this highly selected and arguably desperate patient population, LNF is the optimal treatment. This is in contrast to the literature and expert opinion, which suggest that LNF be avoided in this population due to poor efficacy. A prespecified subgroup analysis showed that patients with reflux hypersensitivity alone benefited from LNF, although this finding is hypothesis-generating and requires further investigation. Surgery for a functional disease like reflux hypersensitivity should be considered only with caution.

A key message from the trial is that true PPI-refractory [gastroesophageal reflux disease] GERD is uncommon: Only 21% of screened patients met the rigorous and objective eligibility criteria. Thorough evaluation of patients labeled as such will identify a substantial number who neither require nor would benefit from escalation to LNF. We recommend that patients be referred for endoscopy with biopsy, esophageal manometry, and impedance-pH testing before considering LNF.

It is surprising that the primary outcome in the trial was the subjective GERD-[Health-Related Quality of Life] HRQL questionnaire. The known marked placebo response to surgery may have inflated the superiority of LNF detected over medical therapy. Impedance-pH testing at 1 year, even as a secondary end point, would have been valuable. In fact, this would be the next logical evaluation step for LNF patients who did not achieve adequate remission of symptoms.

Physicians should not change their practice based on these results until they are confirmed by studies assessing objective primary end points. Meanwhile, patients should receive a thorough work-up to detect other causes of unresponsiveness to PPIs before considering referral for surgery.