Meta-Analysis
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World J Gastroenterol. Mar 7, 2014; 20(9): 2412-2419
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2412
Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: A meta-analysis
Li-Hua Ren, Wei-Xu Chen, Li-Juan Qian, Shuo Li, Min Gu, Rui-Hua Shi
Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Li-Juan Qian, Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Author contributions: Ren LH, Chen WX, Qian LJ and Li S performed the research; Ren LH wrote the manuscript; Gu M contributed new reagents and analytical tools; Shi RH designed the study.
Supported by A grant from the Innovative Team Project to Shi RH, No. CX11
Correspondence to: Rui-Hua Shi, MD, PhD, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. ruihuashi@126.com
Telephone: +86-25-83674636 Fax: +86-25-83674636
Received: October 26, 2013
Revised: December 3, 2013
Accepted: January 2, 2014
Published online: March 7, 2014
Processing time: 130 Days and 15.2 Hours
Abstract

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD).

METHODS: PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy.

RESULTS: Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded.

CONCLUSION: Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.

Keywords: Gastroesophageal reflux diseases; Proton pump inhibitors; Prokinetics; GABA-B receptor agonists; Treatment; Meta-analysis

Core tip: Proton pump inhibitors (PPIs) are generally accepted as the standard treatment of care for gastroesophageal reflux disease (GERD). However, many patients undergoing PPI treatment have no effective symptomatic relief. Although many studies have shown the clinical efficacy of adding prokinetics to PPI therapy in GERD, others have shown no therapeutic benefit. The efficacy and safety of combined prokinetic and PPI therapy for GERD remain controversial. In this retrospective meta-analysis, we find no advantage for the addition of prokinetics to a PPI therapeutic regimen, relative to PPI alone. However, combination therapy may improve symptom score and patient quality of life.