Current management of gastro-oesophageal reflux disease-treatment costs, safety profile, and effectiveness: a narrative review

Abstract

Background: The purpose of this study was to review the current management of gastro-oesophageal reflux disease (GORD), including treatment costs, safety profile and effectiveness.

Methods: A literature review was performed of randomized-controlled trials, systematic reviews, Cochrane reports and National/Societal guidelines of the medical, endoscopic and surgical management of GORD. Proton pump inhibitor (PPI) prescribing patterns and expenditure were reviewed in different countries, including Australia, Canada, New Zealand, UK and USA.

Results: Proton pump inhibitors (PPIs) are primarily indicated for control of GORD, Helicobacter pylori eradication (combined with antibiotics), preventing NSAID-induced gastrointestinal bleeding and treating peptic ulcer disease. There is widespread overprescribing of PPIs in Western and Eastern nations in terms of indication and duration, with substantial expense for national health providers. Despite a favourable short-term safety profile, there are observational associations of adverse effects with long-term PPIs. These include nutrient malabsorption, enteric infections and cardiovascular events. The prevalence of PPI use makes their long-term safety profile clinically relevant. Cost-benefit, symptom control and quality-of-life outcomes favour laparoscopic fundoplication rather than chronic PPI treatment. Laparoscopic fundoplication in long-term management of PPI-responsive GORD is supported by SAGES, NICE and ACG, and PPI-refractory GORD by AGA and SAGES guidelines. The importance of establishing a definitive diagnosis prior to invasive management is emphasized, especially in PPI-refractory heartburn.

Conclusions: We examined evidence-based guidelines for PPI prescribing and deprescribing in primary care and hospital settings and the need for PPI stewardship and education of health professionals. This narrative review presents the advantages and disadvantages of surgical, endoscopic and medical management of GORD, which may assist in shared decision making and treatment choice in individual patients.This paper was presented (GS020) at the 88th RACS Annual Scientific Conference, 6-10 May, 2019.

Figure 1.

Mechanisms of potential risks associated with PPIs [24]. Blue boxes represent effects that are observed. Green boxes represent effects that are weakly associated with PPI use. Pink boxes represent hypothetical effects that have not been recognized or observed in association with PPI use. Black arrows are established linkages, whereas red arrows are proposed unproved links. ECL, enterochromaffin-like; SBP, spontaneous bacterial peritonitis; SIBO, small intestinal bacterial overgrowth.

Figure 2.

Summary of evidence for the associations between PPI use and adverse outcomes in systematic reviews with meta-analyses categorized as the most comprehensive for each outcome [31]. Bar charts are presented based on outcome type: (A) bone-related outcomes, (B) kidney-related outcomes, (C) infection outcomes, (D) cardiovascular and mortality outcomes, (E) cancer, (F) gastrointestinal outcomes, (G) neurological outcomes. Data are based on observational studies, unless otherwise noted. *Associations found to be statistically significant for PPI use and adverse outcome (P < 0.05).

Figure 3.

Approach to the management of patients with heartburn refractory to PPI therapy [47]

Figure 4.

Weighted means for percentage of patients off PPI therapy after MSA, RFA, TIF, and fundoplication [49]. MSA, magnetic sphincter augmentation; PPI, proton-pump inhibitor; RFA, radiofrequency ablation; TIF, transoral incisionless fundoplication. In long-term follow-up (5 years), both TIF and RFA had progressive failure rates for keeping patients off PPIs, as compared with both fundoplication and MSA.

Figure 5.

One-way sensitivity analysis according to various time horizons [83]. Cost comparison model (US$) between PPI and laparoscopic anti-reflux surgery in a patient aged 50 years old with severe GORD who required a continuous double dose of PPIs. The overall time horizon was 10 years and all estimates were discounted at 5% per year. Laparoscopic anti-reflux surgery became less expensive than continuous PPIs after 9 years. Reprinted from J Neurogastroenterol Motil 2020;26:215–23 with permission.

Figure 6.

Thirty-year cost comparison (US$) between each strategy at varying PPI costs [56]. In the base model at a 6-monthly over-the-counter generic omeprazole 20 mg bid cost of US$204, PPI therapy was the least expensive option, but REA and LNF were the most cost-effective treatment options over 30 years. When the PPI cost exceeded US$540/6 months, Nissen fundoplication became the most cost-effective treatment. PPI, proton-pump inhibitor; LNF, laparoscopic Nissen fundoplication; REA (Stretta^®), radiofrequency energy application to the lower oesophageal sphincter; TIF (EsophyX^®), transoral incisionless fundoplication.