Gut 58:295-309 doi:10.1136/gut.2007.145581
  • Recent advances in clinical practice

Management of heartburn not responding to proton pump inhibitors

  1. R Fass1,
  2. D Sifrim2
  1. 1
    The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System and University of Arizona, Tucson, Arizona, USA
  2. 2
    The Center for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium
  1. Professor R Fass, University of Arizona, The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System, GI Section (1-111-GI), 3601 S. 6th Avenue, Tucson, Arizona 85723-0001, USA; Ronnie.Fass{at}


    Patients with gastro-oesophageal reflux disease (GORD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. Various underlying mechanisms have been shown to contribute to the failure of PPI treatment. These include weakly acidic reflux, duodenogastro-oesophageal reflux, residual acid reflux and functional heartburn, as well as others. Diagnostic evaluation of patients with GORD who have failed PPI treatment may include an upper endoscopy, pH testing and oesophageal impedance with pH monitoring. Commonly, doubling the PPI dose or switching to another PPI will be pursued by the treating physician. Failure of such a therapeutic strategy may result in the addition of a transient lower oesophageal sphincter reducer or pain modulator. Anti-reflux surgery may be suitable for a subset of carefully studied patients.


    • Competing interests: Declared. RF is the recipient of research grants from AstraZeneca, Wyeth and Takeda; is a speaker for AstraZeneca; and a consultant for AstraZeneca, Takeda, Eisai, Proctor & Gamble, Vecta, Addix, Xenoport and Pfizer. DS is the recipient of a research grant from Sandhill Scientific and AstraZeneca.