Introduction: Potassium-competitive acid blockers are effective against proton pump inhibitor-refractory gastroesophageal reflux disease; however, their long-term use is associated with economic disadvantages. Endoscopic procedures may reduce potassium-competitive acid blocker use. This study aimed to determine the optimal treatment strategy for patients with proton pump inhibitor-refractory gastroesophageal reflux disease from a cost-effectiveness perspective. Methods: Using a Markov state transition model to simulate symptom changes in patients with proton pump inhibitor-refractory gastroesophageal reflux disease, the cost-effectiveness of two strategies was compared: endoscopic treatment (anti-reflux mucosectomy or endoscopic submucosal dissection for gastroesophageal reflux disease) followed by potassium-competitive acid blocker versus medication with high-dose potassium-competitive acid blocker. In both strategies, potassium-competitive acid blocker maintained symptoms at the lowest controllable dose. The time horizon varied from 10 to 50 years. The quality-adjusted life year and incremental cost-effectiveness ratio were calculated. Willingness to pay was set at 5,000,000 Japanese yen. Results: The quality-adjusted life years gained were 0.90 and 0.95 for the endoscopic treatment and medication strategies, respectively. The incremental cost-effectiveness ratio varied with the follow-up period after the initial treatment, with the endoscopic treatment strategy being more cost-effective than the medication strategy at ≥50 years of follow-up. A dose reduction success rate of <84.1% for high-dose potassium-competitive acid blocker and an endoscopic treatment success rate of >66.8% were required to determine the superiority of the endoscopic treatment strategy at the 50-year follow-up after treatment. Conclusions: The endoscopic treatment strategy is not cost-effective unless the patient is followed up for >50 years after the initial treatment.

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