Article Text

Download PDFPDF
Response of unexplained chest pain to proton pump inhibitor treatment in patients with and without objective evidence of gastro-oesophageal reflux disease
  1. Peter J Kahrilas1,
  2. Nesta Hughes2,
  3. Colin W Howden1
  1. 1Division of Gastroenterology and Hepatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
  2. 2Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK
  1. Correspondence to Dr Peter J Kahrilas, Division of Gastroenterology and Hepatology, Northwestern University, Feinberg School of Medicine, 676 N Saint Clair St, Suite 1400, Chicago, IL 60611-2951, USA; p-kahrilas{at}


Introduction Unexplained chest pain is potentially attributable to gastro-oesophageal reflux disease (GORD) or oesophageal motility disorders. Reflux chest pain may occur without heartburn. We explored the response of unexplained chest pain to proton pump inhibitor (PPI) therapy in randomised clinical trials (RCTs), differentiating patients with and without objective evidence of GORD.

Methods PubMed and Embase were systematically searched for RCTs that reported chest pain response to PPIs in patients who had had pH-monitoring and/or endoscopy to differentiate GORD-positive from GORD-negative subpopulations. Heterogeneity among studies was assessed using the Cochran Q and I2 statistics, and a fixed effect model was applied. Possible publication bias was assessed by Egger's test.

Results Six RCTs met the inclusion criteria. All used 24 h pH monitoring and/or endoscopy to define GORD-positive patients and improvement in chest pain to define response (five used ≥50%; one used ≥20%). The therapeutic gain of >50% improvement with PPIs relative to placebo was 56–85% in GORD-positive and 0–17% in GORD-negative patients. The RR of >50% improvement in chest pain with PPI versus placebo was 4.3 (95% CI 2.8 to 6.7; p<0.0001) for GORD-positive and 0.4 (95% CI 0.3 to 0.7; p=0.0004) for GORD-negative patients. Concomitant heartburn varied among trials from being an exclusion criterion to being essentially concordant with GORD-positive status.

Conclusions Unexplained chest pain in patients with endoscopic or pH-monitoring evidence of GORD tends to improve, but not resolve, with PPI therapy, whereas GORD-negative patients have little or no response. Heartburn was a poor predictor of whether patients with chest pain were GORD-positive or GORD-negative by objective testing.

  • Chest pain
  • Gastroeso phageal reflux
  • proton pump inhibitors

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding NH was supported by an unrestricted educational grant from AstraZeneca R&D Mölndal, Sweden. Data from this study was accepted as a poster presentation at Digestive Disease Week 2011.

  • Competing interests PJK has acted as a consultant for AstraZeneca, Eisai, EndoGastric Solutions, Ironwood, Novartis, Movetis, Revalesio and XenoPort. NH is an employee of Oxford PharmaGenesis™ Ltd. CWH has acted as a consultant for Takeda, XenoPort, Santarus, Procter & Gamble, Merck/Schering-Plough Healthcare, Boehringer Ingelheim, Novartis Consumer Health, Novartis Oncology, Otsuka and KV Pharmaceuticals, and as a speaker for Takeda, Novartis and Otsuka.

  • Provenance and peer review Not commissioned; externally peer reviewed.