Potassium-competitive Acid Blockers in Gastroesophageal Reflux Disease and Functional Dyspepsia: A Korean Expert Review With Original Meta-analyses.

For heartburn or regurgitation persisting despite PPI therapy, current practice (ACG 2022 GERD guideline, still the operative ACG guideline, plus the AGA 2022 personalized-GERD CPU) is to first optimize the PPI: confirm adherence, dose 30-60 minutes before meals, escalate to twice-daily dosing or switch agents for an 8-week trial. Empiric escalation to vonoprazan/P-CAB is NOT a routine pre-testing step: the AGA 2024 P-CAB clinical practice update advises against P-CABs as first-line therapy and reserves them for PPI failure with confirmatory GERD evidence (LA grade B or worse erosive esophagitis, biopsy-proven Barrett's, peptic stricture, or acid exposure time >6%). If symptoms persist after optimization, perform EGD (ideally 2-4 weeks off PPI when GERD is unproven) with esophageal biopsies to exclude EoE (>=15 eos/hpf; the ACG 2025 EoE guideline has removed the PPI trial from the diagnostic pathway) and then physiologic testing per Lyon Consensus 2.0: in unproven GERD, ambulatory reflux monitoring OFF therapy, applying Lyon 2.0's modality-specific thresholds -- on catheter-based single-day (24-hour) pH or pH-impedance, AET >6% is conclusive for GERD, 4-6% is inconclusive, and <4% argues against GERD; on prolonged wireless (Bravo, up to 96-hour) monitoring, AET >6% on >=2 days is conclusive for GERD while AET <4% on all days excludes it, and a study meeting neither threshold is inconclusive (the number of days with AET <4% carries prognostic weight for PPI discontinuation) -- and, in either modality, a normal-AET (<4%) study with positive symptom association indicates reflux hypersensitivity or, without it, functional heartburn; in previously proven GERD, pH-impedance ON optimized therapy, where AET >4% plus >80 reflux episodes defines actionable refractory GERD (MNBI <1500 ohms supportive, >2300 ohms against). High-resolution manometry per Chicago Classification 4.0 (still current) excludes achalasia and major motility disorders and is required before anti-reflux surgery. Therapy is phenotype-directed: surgical or endoscopic anti-reflux intervention for confirmed refractory pathologic reflux, and neuromodulators with or without brain-gut behavioral therapy for reflux hypersensitivity and functional heartburn.