Acid peptic disorder compass: An Indian expert consensus on comprehensive management

Abstract

Overlapping pathophysiological mechanisms of gastroesophageal reflux disease, peptic ulcer disease, and functional dyspepsia often limit the symptom-based diagnosis precision. Additionally, the easy availability of over-the-counter proton pump inhibitors has increased the instances of self-diagnosis and self-treatment in the Indian population. Prolonged, unsupervised use of acid suppressants may reduce the treatment efficacy and increase the risk of adverse effects, such as infections and nutrient deficiencies. Therefore, a task force of 13 leading gastroenterologists under the Society for Clinical Gastroenterology reviewed the existing evidence to develop expert consensus statements for differentiating the overlapping symptoms of acid peptic disorders (APD) and guiding the rational use of acid-suppressive therapies. The available literature was searched and summarized in order to identify the relevant data. The pieces of evidence were discussed, validated, and revised in a face-to-face interaction of the task force members that led to a final set of 20 consensus statements. A comprehensive algorithm of the APD 360° compass was prepared for diagnosis and effective management of APDs based on the recommendations. This algorithm may guide physicians in India for timely diagnosis and appropriate medical interventions, thereby improving the patients’ quality of life.

Key Words: Acid peptic disorders; Consensus; Dyspepsia; Gastroesophageal reflux disease; Peptic ulcer; Potassium-competitive acid blockers; Proton pump inhibitors; India

Core Tip: Overlapping mechanisms in gastroesophageal reflux disease, peptic ulcer, and functional dyspepsia often hinder accurate symptom-based diagnosis. In India, easy access to over-the-counter proton pump inhibitors has fuelled self-diagnosis and prolonged unsupervised use, which reduces treatment efficacy and increases risks of infections and nutrient deficiencies. To address this, a task force of 13 gastroenterologists under the Society for Clinical Gastroenterology reviewed evidence and developed 20 expert consensus statements. Through literature review and discussion, they proposed the acid peptic disorders 360° compass algorithm for distinguishing symptoms and guiding rational acid-suppressive therapy. This algorithm aims to improve timely diagnosis, treatment, and the patient’s quality of life.

INTRODUCTION

Acid peptic disorders (APD) encompass conditions such as gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD), often related to Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID), and represent a major global health burden[1,2]. Functional dyspepsia (FD) is another common gastrointestinal (GI) disorder that often co-exists with GERD due to their common pathophysiology[3]. Worldwide prevalence of dyspepsia is around 20%-30%, while in India, according to different studies, it widely varies between 7.6%-49%[4]. The reported prevalence of GERD is 8%-19% in India[5]. Precise diagnosis and prompt management of APD is crucial as it impacts the quality of life as well as work productivity of the patients[6].

Gastric acid suppression is the mainstay treatment for APD[7] and includes antacids, histamine-H2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), and potassium-competitive acid blockers (PCABs)[8]. PPIs are widely used as initial treatment for APD in clinical practices because of their favorable efficacy, tolerability, and easy availability[9]. Vonoprazan, a recent United States Food and Drug Administration-approved PCAB, is considered to have advantages over PPIs[10]. However, management of APDs is challenging due to overlapping symptoms[3,11], self-medication[12], refractory cases, long-term drug risks, regional healthcare disparities, and antibiotic resistance[1]. Throughout the years, the over-the-counter availability of PPIs and self-management has possibly delayed the treatment for a more serious underlying condition[12]. In addition, chronic use of PPIs without any supervision may lead to acute interstitial nephritis, hypergastrinemia, infections, and hyponatremia[13]. Selecting the right treatment for the right patient, comorbidities, patient adherence to medication regimens, and potential side effects pose additional challenges[14]. Moreover, rural healthcare in India faces compounded challenges due to geographical barriers, limited access to diagnostics, and a shortage of specialized care, often leading to delayed treatment[15]. These difficulties in managing APDs in India underscore the critical need to provide healthcare professionals with a comprehensive, evidence-based update on the APDs. Therefore, the APD 360° compass consensus study aims to provide evidence-based, consensus-driven clinical tool designed to streamline diagnosis, stratify patients, and guide personalized management of APDs through a structured algorithm and wheel diagram. The APD 360° compass offers a comprehensive, integrated overview of GERD, PUD, H. pylori infection, and FD to support clinical decision-making.

METHODOLOGY

The development of the APD 360° compass was guided by a structured and evidence-based process led by a dedicated task force comprising 13 gastroenterologists under the aegis of the Society for Clinical Gastroenterology. This initiative aimed to formulate consensus-based recommendations for the diagnosis and management of APDs in the Indian population.

Formation of the task force

The task force members were selected based on their geographic representation across India, clinical expertise in APDs, and academic contributions to the field. Two senior gastroenterologists, identified for their subject-matter expertise and interest, served as moderators. The moderators defined the scope of the consensus, which included GERD, PUD, H. pylori infection, and FD. These categories were further subdivided into clinically relevant patient profiles such as refractory, recurrent, severe, and complicated cases.

Literature review and statement development

A comprehensive literature search was performed using PubMed and Google Scholar to identify relevant publications from 2010 to 2025. The search strategy targeted clinical trials, systematic reviews, meta-analyses, observational and comparative studies, and established clinical guidelines. Keywords included: Acid peptic disorders, acid suppression therapies (PPIs, H2RAs, PCABs), GERD management, peptic ulcer treatment, H. pylori eradication, FD, and Indian consensus guidelines. The moderators synthesized the evidence and guiding principles to draft 22 preliminary consensus statements across 11 subtopics, which were then assigned to respective task force members for in-depth review.

Consensus meeting

An in-person consensus meeting of approximately eight hours was conducted, during which each assigned subtopic was presented and discussed in detail. The task force deliberated on the evidence, assessed the validity of each statement, and revised it accordingly. This collaborative discussion resulted in the refinement of the original 22 statements to a final set of 20 consensus statements. Following the meeting, further discussions and clarifications were carried out via email to finalize the consensus statements before initiating the voting process.

Consensus validation

The finalized statements were circulated via email to all task force members for voting using an online platform (Google forms). Each member was asked to rate the statements using a five-point Likert scale: A - accept completely; B - accept with some reservation; C - accept with major reservation; D - reject with some reservation; and E - reject with major reservation. A statement was considered to have achieved consensus if ≥ 80% of respondents rated it as either “accept completely” or “accept with some reservation” (i.e., A or B).

Finalization and manuscript preparation

Voting responses were collated and analyzed. The manuscript was then drafted based on the finalized consensus statements and supporting evidence, followed by a comprehensive review and approval from all task force members prior to submission for publication. Figure 1 illustrates the consensus development process, including literature review, statement formulation, panel discussions, and voting. An APD management algorithm wheel has been prepared based on the guidelines and consensus recommendations that have examined different modalities of therapy for various APD.

Figure 1  Flow chart representation of consensus development.

RESULT AND DISCUSSION

Pharmacologic basis of acid suppression

The pharmacologic management of APDs has evolved significantly, with a clearer understanding of the pharmacodynamics and clinical utility of acid suppression agents. The recommended regimen for gastric acid suppression with H2RA, PPIs, PCABs, and prokinetics is shown in Table 1[16-28]. The H2RAs, though effective in mild cases, are limited by tachyphylaxis with prolonged use[29]. PPIs remain the cornerstone for most APDs due to their potent and sustained acid suppression; however, interpatient variability in metabolism and delayed onset can impact the outcomes[30,31]. The pharmacokinetic properties of the PPIs[32-34] are presented in Table 2.

Table 1 Acid suppression therapy for acid peptic disorders.

Ref.	GERD	Reflux/erosive esophagitis	NERD	PUD/H. pylori eradication
Bhatia et al[16], 2020; Yadlapati et al[17], 2022; Iwakiri et al[18], 2022; ZANTAC® SmPC[19]	Rabeprazole 20 mg OD	Vonoprazan 20 mg OD for 4 weeks (in mild condition)	Ranitidine 150 mg TID	Vonoprazan 20 mg BD (dual/triple therapy)
Iwakiri et al[18], 2022; NEXIUM SmPC[20]; PEPCID® SmPC[21]	Esomeprazole 20/40 mg OD	Vonoprazan 20 mg + prokinetics (in severe condition) for 8 weeks	Famotidine 20 mg BD	Esomeprazole 40 mg OD
Bhatia et al[16], 2020; Yadlapati et al[17], 2022; Farrell et al[22], 2017	Dexlansoprazole 30 mg OD	Esomeprazole 40 mg OD	Esomeprazole 20 mg OD	Rabeprazole 20 mg OD (post-breakfast) for up to 4 weeks
PROTONIX SmPC[23]; DEXILANT SmPC[24]; Central Drugs Standard Control Organization Government of India[25]	Pantoprazole 40 mg OD	Dexlansoprazole 30/60 mg OD	Dexlansoprazole 30 mg OD	Ilaprazole 5-10 mg OD
ZANTAC® SmPC[19]; PEPCID® SmPC[21]; ACIPHEX® SmPC[26]; PRILOSEC SmPC[27]	Famotidine 40 mg OD	Ranitidine 150 mg QID	Rabeprazole 20 mg OD	Omeprazole 20 mg BD or 40 mg OD
ZANTAC® SmPC[19]; PEPCID® SmPC[21]; Central Drugs Standard Control Organization Government of India[28]	Ranitidine 150 mg BD	Famotidine 20/40 mg TID		Lafutidine 5-10 mg

BD: Twice-daily; GERD: Gastroesophageal reflux disease; GU: Gastric ulcer; NERD: Non-erosive reflux disease; OD: Once-daily; PUD: Peptic ulcer disease; QID: Four times a day; TID: Three times a day; H. pylori: Helicobacter pylori.

Table 2 Pharmacokinetics of proton pump inhibitors.

Agents	Bioavailability (%)	Tmax (hour)	Cmax (mg/mL)	Protein binding (%)	T1/2 (hour)	pKa	AUC 0-24 (mg/hour/L)	V (L/kg)	CL (mL/minute)
Esomeprazole	64-90	1.5	1.5	97	1-1.5	4.0	2.0	160-330	1.3-1.6
Dexlansoprazole	-	4-5	-	96	1-2	4.0	-	-	-
Pantoprazole	77	2-3	2.5	98	1-1.9	3.9	5.0	90-225	0.8-2.0
Rabeprazole	52	2-5	0.4	96.3	1-2	5.0	0.8	-	0.6-1.4
Omeprazole	30-40	0.5-3.5	0.7	95	0.5-1	4.0	2.0	400-620	0.5-1.2
Lansoprazole	80-85	1.7	0.5-1.0	97	1.6	4.0	2.5	400-650	0.9-2.1

AUC: Area under the curve; CL: Clearance; T_max: Time to peak plasma level; C_max: Maximum plasma concentration; T_1/2: Half-life; V: Apparent volume of distribution.

The PCABs reversibly block the potassium channel pump, inhibiting the gastric acid secretion and maintaining elevated intragastric pH for a long time[35]. Vonoprazan (a pyrrole derivative) and tegoprazan (a benzimidazole) are currently available PCABs in the market[8]. Vonoprazan fumarate is a food-independent, first-in-class PCAB. It is commonly used as an alternative to PPIs for H. pylori eradication[35]. Vonoprazan offers a novel mechanism of action with rapid, reversible, consistent, and potent acid suppression. This helps in improving symptom control and healing, particularly in refractory cases or those with nocturnal acid breakthrough[36]. Within two hours of administration, vonoprazan can reach maximum concentration in plasma, and its concentration is 10⁸-fold higher in the secretory canaliculus of the parietal cell, compared to the plasma[37]. Mean half-life is 7.9 hours for vonoprazan and 1.4 hours for PPI lansoprazole, thus vonoprazan has significantly more potent inhibition of intragastric acidity (24-hour holding-time ratio for pH > 4) than PPI lansoprazole[38]. A tailored, patient-centric approach combining pharmacologic precision with behavioural modification optimizes long-term control of APDs[39]. Moreover, lifestyle interventions including dietary adjustments, weight management, sleep posture, and avoidance of known triggers (e.g., NSAIDs, alcohol, and smoking) remain integral to comprehensive care[40]. Inclusion of antioxidants, high fiber and protein in dietary plan, avoiding caffeine, fatty/spicy foods, milk, chewing gum, citrus fruits, or high intake of salt, and stress alleviation will help in maintaining the overall health of the patients[41].

Acid suppression and treatment of GERD

GERD is classified into erosive reflux disease (ERD), characterized by esophageal mucosal injuries, and non-ERD (NERD), having symptoms only, but no visible abnormalities[18]. The 2020 Indian Society of Gastroenterology and Association of Physicians of India consensus guidelines suggested a classical symptom (heartburn and sour regurgitation)-based diagnosis of GERD[16]. The 2022 American College of Gastroenterology (ACG) guidelines recommended diagnostic endoscopy in patients whose classic GERD symptoms (recurrent reflux of stomach contents, heartburn, and/or regurgitation) are not responding to PPIs, only after stopping PPIs for at least 2 to 4 weeks[31]. No response or improvement in GERD symptoms following an 8-week PPI regimen is termed as refractory GERD[42]. The updated 2024 ACG guideline also suggested endoscopy as the initial evaluation in patients with dysphagia, other alarm symptoms like weight loss, GI bleeding, etc., or Barrett esophagus[43]. An algorithm for the diagnosis and treatment of GERD[18,44] is provided in Figure 2.

Figure 2 Diagnosis and treatment algorithm of gastroesophageal reflux disease. EE: Erosive esophagitis; ERD: Erosive reflux disease; GERD: Gastroesophageal reflux disease; NERD: Non-erosive reflux disease; RE: Reflux esophagitis; PCAB: Potassium-competitive acid blockers; PPI: Proton pump inhibitors; OD: Once-daily.

Initial therapy of GERD: For patients with typical GERD without alarm symptoms, empiric therapy with once-daily PPIs before a meal for 4-8 weeks is recommended.

Statement 1: Once-daily oral PCAB administered independent of a meal can be an alternative to PPI. Level of agreement: A - 69.2%, B - 15.4%, C - 15.4%. A network meta-analysis supported full/standard doses of esomeprazole (40 mg/day for 4-8 weeks) as the first-line GERD therapy[45], while the 2024 Brazilian clinical guideline advised that over 8-week empirical PPI use should be limited to selected cases[46]. The PCABs, including vonoprazan, showed promising results in ERD, NERD, and PPI-resistant GERD[47]. Vonoprazan achieved 87.5% mucosal healing at 20 mg/day and 76.2% relapse prevention at 10 mg/day[48]. The panel recommended starting with once-daily PPIs for 4-8 weeks or PCABs for typical GERD without alarm features.

Statement 2: For the initial treatment of GERD, the efficacy of PCABs is comparable to that of PPIs. Level of agreement: A - 84.6%, B - 15.4%. The panel acknowledged that both PPIs and PCABs (e.g., vonoprazan) are effective and safe options for initial GERD therapy, as supported by the 2024 Brazilian clinical guidelines and other trials[46]. Vonoprazan demonstrated non-inferior efficacy to PPIs in treating erosive esophagitis and GERD[49,50], with a comparable safety profile confirmed across 14 clinical trials[51]. Additionally, vonoprazan therapy resulted in superior symptom relief and patient satisfaction in PPI-refractory GERD cases[52].

Statement 3: For patients with GERD who respond to 4-8 weeks of therapy, de-escalate the dose of PPI/PCAB or discontinue PPIs or PCABs. Level of agreement: A - 92.3%, B - 7.7%. The 2022 ACG guideline conditionally recommended attempting to discontinue PPIs in patients whose typical GERD symptoms improve following an 8-week empirical trial of PPI therapy[31]. The American Gastroenterological Association suggested dose tapering or abrupt discontinuation of PPIs, solely depending on the indication of PPI withdrawal[53]. The panel also discussed the factors that should be considered while de-escalating or discontinuing PPIs or PCABs in GERD patients. Patients having uncomplicated or NERD on a twice-daily PPI dose can be de-escalated to a once-daily dose, along with monitoring of the dose response. In case of good response, the maintenance dose can go down further to half of the once-daily dose and subsequently completely stopped unless symptoms return. The time for this weaning process may vary based on the physician’s discretion[54]. Tapering the PPI dose may help in successfully discontinuing the medication[55]. Implementation of a de-escalation protocol, provision of training and education for the providers as well as patients, could help in accomplishing discontinuation of PPIs and minimizing the rebound acid hypersecretion. The patients should be aware of the reappearing symptoms and prescribed H2RAs or antacids when required[56].

Statement 4: PCABs appear to be equally suitable for intermittent and on-demand use for acid suppression in the setting of GERD. Level of agreement: A - 38.5%, B - 61.5%. The 2022 Japanese Society of Gastroenterology (JSGE) guideline recommended a standard dose of PPI or PCAB (including on-demand therapy) as the initial therapy for mild reflux esophagitis[18]. The task force members discussed that PCABs are equally suitable for acid suppression when used intermittently or on demand. In patients with NERD, on-demand vonoprazan is a potential alternative to continued daily acid suppression therapy in relieving episodic heartburn[57]. A randomized trial reported that vonoprazan provided quick relief from heartburn symptoms of NERD[58]. Various doses of on-demand vonoprazan (10 mg, 20 mg, and 40 mg) have been proven to improve NERD symptoms within 3 hours of administration[59]. The therapeutic action of PCABs does not depend on a meal or require acidic pH, and the acid inhibition is irreversible, hence it is effective even when a dose is given in an intermittent manner[60]. Intermittent PCAB therapy is effective in healing esophagitis with additional benefits of cost-effectiveness because of fewer numbers of physician visits and required medication days[61].

Statement 5: The safety of PCABs during pregnancy has not been established. Level of agreement: A - 84.6%, B - 15.4%. Data for PCABs in pregnant and lactating populations are sparse[9]. The American Gastroenterological Association clinical practice update discussed that there are limited safety data for PCABs in pregnant and lactating populations. However, no toxicity of vonoprazan was observed in an animal study[62]. It is recommended to design more studies on the efficacy and safety of PCABs in pregnant women. Use of various acid suppressants in patients with renal/hepatic impairment is summarized in Table 3[19,21,63].

Table 3 Use of acid suppressants in special populations.

Treatment	Indication	Dose/frequency	Risk/conditions
Renal impairment
Ranitidine[19]	GERD	150 mg OD	Risk of toxic reactions: In elderly patients with reduced renal function, in patients with hepatic dysfunction
Famotidine[21]	Erosive esophagitis	20 mg OD or 40 mg every other day	Risk of CNS adverse reactions and QT prolongation in moderate and severe renal impairment
	GU/DU
Vonoprazan[63]	Erosive esophagitis	10/20 mg OD	Not recommended: In severe renal impairment (eGFR < 30 mL/minute), for maintenance of healed erosive esophagitis
	H. pylori eradication	20 mg BD
Hepatic impairment
Vonoprazan[63]	Erosive esophagitis	10/20 mg OD	Not recommended for H. pylori eradication in moderate to severe hepatic impairment
	H. pylori eradication	20 mg BD

BD: Twice-daily; CNS: Central nervous system; DU: Duodenal ulcer; eGFR: Estimated glomerular filtration rate; GERD: Gastroesophageal reflux disease; GU: Gastric ulcer; OD: Once-daily; H. pylori: Helicobacter pylori.

Choice of acid suppressant for recurrent and refractory symptoms: Statement 6: In patients with confirmed GERD, who do not respond to once-daily PPIs, options include twice-daily PPIs, dual-release PPIs, or PCABs. Level of agreement: A - 76.9%, B - 23.1%. While most GERD patients respond to once-daily PPI therapy, some require intensified treatment due to suboptimal response[64]. Many non-responders have functional esophageal disorders such as reflux hypersensitivity or functional heartburn[65]. Studies showed that twice-daily rabeprazole improved symptoms and quality of life more than once-daily dosing, with higher no-recurrence rates in moderate-to-severe erosive esophagitis cases[66,67]. Vonoprazan (20 mg) also achieved 87.5% mucosal healing in PPI-resistant cases, with 76.2% relapse prevention on maintenance[48]. Based on these findings, the panel recommended considering twice-daily PPIs, dual-release PPIs, or PCABs like vonoprazan for confirmed GERD unresponsive to standard PPI therapy.

Statement 7: Patients who do not respond to 4-8 weeks of empiric PPI or PCAB therapy require further investigations and evaluation. Level of agreement: A - 84.6%, B - 15.4%. The task force recommended further investigation and evaluation in patients not responding to 4-8 weeks of empiric PPI or PCAB therapy. The 2022 ACG guideline strongly recommended performing a diagnostic endoscopy, preferably after withholding PPIs for 2 to 4 weeks, in patients with typical GERD symptoms who fail to respond to an 8-week empiric trial of PPIs or whose symptoms recur upon discontinuation of therapy[31].

Statement 8: For symptomatic treatment of nocturnal acid breakthrough, the use of H2RA at bedtime, in addition to a PPI, is beneficial; alternative treatment options can be twice-daily PPIs, dual-release PPIs, or PCABs. Level of agreement: A - 84.6%, B - 15.4%. Addition of an H2RA to PPI demonstrated improvement in overall symptoms (72%), night-time reflux symptoms (74%), and GERD-associated sleep disturbance (67%)[68]. The same findings of a decrease in the prevalence rate of nocturnal gastric acid with the addition of an H2RA to PPI have been suggested by a Cochrane review[69]. Combination therapy of bedtime H2RA and PPI is superior to twice-daily PPI in controlling gastric acid secretion and nocturnal acid breakthrough[70]. However, H2RA efficacy may diminish over time due to tachyphylaxis[29], necessitating alternative strategies like PCABs for persistent symptoms. Vonoprazan has greater effectiveness in nighttime acid suppression than esomeprazole, even when compared to tegoprazan[71]. Based on the available evidence and experience of routine practice, the task force members recommended the addition of a bedtime H2RA to PPI for symptomatic treatment of nocturnal acid breakthrough. Additionally, twice-daily PPIs, dual-release PPIs, or PCABs/could be considered.

Acid suppression as maintenance therapy in severe or recurrent GERD: Statement 9: In patients with severe erosive esophagitis on endoscopy (Los Angeles grade C and D), PCABs are preferred over PPI for healing of esophagitis and symptom relief. Such patients require long-term maintenance therapy with PPIs or PCABs. Level of agreement: A - 92.3%, B - 7.7%. Recent meta-analyses confirmed vonoprazan as an effective and safe alternative to PPIs, especially in PPI-refractory GERD[72,73]. Vonoprazan offers faster acid suppression and superior healing of Los Angeles grade C/D erosive esophagitis, compared to PPIs[74,75]. Vonoprazan 20 mg once-daily showed significantly lower treatment failure rates than lansoprazole or omeprazole[75]. Based on the evidence, the panel recommended PCABs as the preferred option for patients with severe erosive esophagitis (Los Angeles grade C/D) for effective healing and symptom control.

Acid suppression in GERD-related complications - peptic stricture and Barrett’s esophagus: Statement 10: In complicated GERD (e.g., Barrett’s esophagus, esophageal peptic stricture), long-term acid suppression therapy with PPIs or PCABs is recommended. Level of agreement: A - 76.9%, B - 7.7%, C - 15.4%. Patients with complicated GERD, such as severe esophagitis, Barrett’s esophagus, or peptic strictures, typically require uninterrupted, long-term PPI therapy for mucosal healing and prevention of progression[31,76]. High-dose esomeprazole showed superior efficacy over pantoprazole in Barrett’s esophagus[77], though evidence on PPIs’ role in preventing progression to dysplasia or cancer remains mixed[78]. Variability in epithelial regeneration across PPIs has been observed[79]. The panel also acknowledged vonoprazan’s potential role and recommended long-term acid suppression with PPIs or PCABs in patients with complicated GERD.

Acid suppression and treatment of PUD

PUD commonly occurs in the stomach (gastric ulcer) or duodenum (duodenal ulcer) and is caused by H. pylori infection or the use of NSAIDs. It may progress to complicated PUD, characterized by acute GI bleeding, if left untreated[80]. Signs and symptoms of PUD include epigastric pain, nausea, vomiting (possibly with blood), anorexia or increased hunger, weight loss, melena, or dyspnea[81]. Uncomplicated PUD, defined as mucosal breaks without bleeding, perforation, or obstruction on endoscopy, may cause anemia without overt bleeding. Timely diagnosis and management are crucial to prevent complications[82]. For ulcers not linked to NSAID use or with active bleeding, infection testing for H pylori is advised[83]. The 2015 European Society of Gastrointestinal Endoscopy (ESGE) guideline recommended immediate assessment of the hemodynamic status of patients presenting with acute upper GI bleeding due to PUD[84]; while the 2021 ACG clinical guideline suggested endoscopy within 24 hours[85]. The 2020 World Society of Emergency Surgery guidelines recommended routine laboratory testing and arterial blood gas analysis for suspected gastroduodenal perforation, a computed tomography scan imaging or chest/abdominal X-ray if computed tomography scan imaging is not available for acute abdomen from suspected perforated peptic ulcer, and imaging with addition of water-soluble contrast (orally/via nasogastric tube) for acute abdomen from suspected perforated peptic ulcer, when free air is not visible in the imaging[86]. Diagnosis and treatment for PUD[30,87-89] are presented in Figure 3.

Figure 3 Diagnosis and treatment algorithm of peptic ulcer disease. AMX: Amoxicillin; GI: Gastrointestinal; H2RA: Histamine-H2 receptor antagonists; MET: Metronidazole; PUD: Peptic ulcer disease; PPI: Proton pump inhibitor; PCAB: Potassium-competitive acid blocker; TC: Tetracycline; H. pylori: Helicobacter pylori.

Choice of acid suppressant in uncomplicated duodenal ulcers and gastric ulcers: Statement 11: For the initial treatment of uncomplicated gastric and duodenal ulcers, oral PPIs or PCABs are recommended for 8-12 weeks. Level of agreement: A - 76.9%, B - 23.1%. The 2020 JSGE guideline recommended PPIs for the treatment of NSAID-induced ulcers in cases where NSAIDs cannot be discontinued[30]. The Japanese national health insurance system only permits use of PPI esomeprazole (20 mg once-daily) for 8 weeks for managing gastric ulcer and 6 weeks for duodenal ulcer[90]. A clinical practice guideline on PPI recommended short-term (2-12 weeks) PPI for peptic ulcer; after that, PPI therapy can be discontinued only if maintenance therapy is not indicated[22]. Vonoprazan could be used over PPIs for concomitant therapy in patients with a high risk of NSAID-induced peptic ulcers[7], or as an alternative to PPI because of its similar tolerability profile in gastric and duodenal ulcer healing, when used for 8 weeks[80]. On the basis of available evidence, the task force members recommended the use of oral PPI or PCABs/vonoprazan for 8-12 weeks in controlling uncomplicated gastric and duodenal ulcers. They further recommended consulting a gastroenterologist in case no optimum response is noticed after 8-12 weeks of PPI or PCABs use.

Statement 12: Patients with a history of PUD receiving long-term NSAIDs or aspirin should undergo evaluation and treatment for H. pylori infection to prevent recurrence of peptic ulcer and complications. Level of agreement: A - 100%, B - 0%. Guidelines suggested testing and eradication therapy for H. pylori to minimize the risk of recurrence and complications in patients with a prior history of PUD, who require long-term NSAIDs[91] or low-dose aspirin[30]. A prospective, randomized controlled trial reported that H. pylori eradication also lowers the recurrence rate of ulcer bleeding in aspirin users[92]. H. pylori eradication significantly reduces ulcer incidence, particularly in NSAID-naïve individuals[93]. However, in patients continuing NSAID therapy, H. pylori eradication alone may not suffice, and additional acid suppression with PPIs might be required[94,95]. Noninvasive evaluation of H. pylori infection through the urea breath test and stool antigen test offers precision in monitoring treatment outcomes without the use of recurrent invasive procedures[96]. The task force group suggested that patients with a history of PUD and receiving long-term NSAIDs or aspirin should undergo evaluation and treatment for H. pylori infection to prevent recurrence and complications. The members also recommended co-administering PPI or PCAB in case NSAIDs cannot be discontinued. The opinion is guideline-supported[30,91].

Choice of acid suppressant in refractory and recurrent PUD: Statement 13: If NSAIDs cannot be discontinued in patients with a history of PUD, co-administration of PPIs or PCABs is recommended for the prevention of ulcer recurrence and complications. Level of agreement: A - 61.5%, B - 38.5%. Long-term NSAIDs, low-dose aspirin, and H. pylori infection are the key risk factors for peptic ulcer bleeding[97]. The panel emphasized evaluating and treating H. pylori in patients on chronic NSAID or aspirin therapy, especially those with prior PUD. Co-administration of acid suppressants, particularly PPIs, is recommended to reduce ulcer recurrence and bleeding risk. A clinical practice guideline from Korea recommended the use of low-dose PPIs for reducing peptic ulcer and its complications in high-risk patients who are taking long-term NSAIDs. Guidelines from Korea and the 2021 JSGE supported low-dose PPIs in high-risk patients on long-term NSAIDs or low-dose aspirin[30,91]. The panel also supported PCABs as effective alternatives to PPIs, with studies showing similar efficacy and safety in preventing NSAID-induced ulcer recurrence[98,99].

Statement 14: In patients at high risk for peptic ulcers, PCABs are equally or more effective than PPIs in preventing ulcer recurrence. Level of agreement: A - 46.2%, B - 53.8%. The panel discussed whether PCABs are equally or more effective than PPIs in preventing ulcer recurrence in patients at high risk for peptic ulcers with reference to current evidence. A systematic review indicated that PCABs are non-inferior to PPIs in preventing ulcer recurrence during NSAID therapy, with comparable safety outcomes[100]. Vonoprazan, a PCAB, prevents drug-induced ulcers and offers faster symptom relief in acid-related disorders[101-103]. Vonoprazan has shown similar effectiveness and long-term safety profile in preventing NSAID-related peptic ulcer recurrence as lansoprazole in at-risk patients[99]. Vonoprazan demonstrated better ulcer healing rates and H. pylori eradication, particularly in H. pylori-positive cases, suggesting its advantage over PPIs in certain clinical contexts[104]. More head-to-head comparisons reflecting the efficacy and safety of PPIs and PCABs in preventing ulcer recurrence are required to guide clinical decision-making and provide better treatment options.

Statement 15: For refractory peptic ulcers persisting after 8-12 weeks of standard anti-secretory therapy and H. pylori eradication, the PPI dose can be doubled, or an alternative PCAB may be considered. Level of agreement: A - 69.2%, B - 30.8%. Despite using standard anti-secretory drug treatment, refractory (for 8 to 12 weeks) peptic ulcers exist, probably due to NSAID use, persistent H. pylori infections, or resistant strains[105]. A 36-week course of oral esomeprazole (20 mg, once- or twice-daily) decreased bleeding from refractory or recurrent ulcer (size ≥ 0.5 cm); however, this needed to be validated when PPIs are no longer continued[106]. In cases where peptic ulcers do not heal despite an adequate course of standard PPI therapy, modifying the treatment approach may be necessary. The panel recommended doubling the PPI dose or an alternative PPI/PCAB therapy in refractory peptic ulcers existing even after 8-12 weeks of standard anti-secretory therapy and H. pylori eradication or a full course of PPI therapy. Evidence from 2009 Korean diagnostic guidelines suggested doubling and extending (additional 6-8 weeks) PPI therapy if ulcer healing is not achieved after 8-12 weeks of standard-dose anti-secretory treatment[105,107].

Acid suppression in bleeding peptic ulcers: Statement 16: In patients with upper GI bleeding, pre-endoscopy intravenous (IV) PPI administration is recommended, especially if early endoscopy or endoscopic expertise is unavailable within 24 hours. Level of agreement: A - 69.2%, B - 30.8%. The 2021 ESGE guideline recommended performing upper GI endoscopy within 24 hours after hemodynamic stabilization, but not urgently within 12 hours[108]. For patients with high-risk stigmata, high-dose IV PPI with a loading dose followed by 72-hour infusion is advised post-endoscopy[109]. Cochrane reviews showed that pre-endoscopy PPI may reduce the need for endoscopic intervention, though its impact on outcomes like mortality or rebleeding is unclear[110,111]. The 2021 ACG also stated initiating PPI at presentation and continuing high-dose therapy post-endoscopy to reduce rebleeding risk[85]. The evidence-based discussion led to the recommendation of administering IV PPI prior to endoscopy, especially when early endoscopy or expertise is unavailable within 24 hours.

Statement 17: Acid suppressive therapy as an adjunct to endoscopic management of bleeding peptic ulcers - during the initial 72 hours, a bolus dose followed by IV PPI infusion or twice-daily PPI or oral PCABs is recommended: (1) Level of agreement: A - 76.9%, B - 23.1%. The 2021 ESGE guideline recommended administering high-dose PPI therapy via IV bolus and continuous infusion (e.g., 80 mg IV bolus followed by 8 mg/hour infusion) for 72 hours in patients with bleeding PUD post-endoscopic hemostasis. Oral/IV bolus dosing twice daily may also be an effective alternative[108]. Oral vonoprazan is a non-inferior alternative to IV PPIs in preventing 30-day rebleeding after endoscopic hemostasis[102]. The 2021 ACG clinical guideline suggested continuous or intermittent high-dose PPI therapy for three days post-endoscopy, followed by twice-daily oral PPI for two weeks to maintain hemostasis and prevent recurrence; in cases of recurrent bleeding, repeat endoscopy or transcatheter embolization is advised[85]. The panel therefore recommended a bolus dose followed by IV PPI infusion, twice-daily PPI, or oral PCABs such as vonoprazan as an adjunct to endoscopic management of bleeding peptic ulcers during the initial 72 hours of bleeding peptic ulcers. High-dose oral PPI is a cost-effective and non-inferior alternative in selected populations; (2) Level of agreement: A - 61.5%, B - 38.5%. Intermittent IV, IV bolus, and oral PPI regimens demonstrated similar clinical effectiveness, suggesting that 72-hour continuous IV infusion may not always be necessary - even in high-risk cases[112]. Similar clinical outcomes between high-dose oral and IV PPIs were observed for preventing rebleeding in high-risk patients[113]. A systematic review and meta-analysis also reported similar efficacy of oral and IV PPIs in preventing rebleeding, reducing the need for surgery, and minimizing mortality across varying ulcer stigmata; oral PPIs also provide additional cost-saving benefits. In addition, patients receiving high-dose oral PPI therapy require fewer blood transfusions, compared to those receiving IV PPIs[114]. Therefore, the panel recommended high-dose oral PPI as a cost-effective and non-inferior alternative to IV PPI therapy when used as an adjunct to endoscopic management of bleeding peptic ulcers. After 72 hours of IV PPI, high-dose oral PPI is recommended for 2-4 weeks to prevent rebleeding or surgery. PCABs may serve as an alternative to high-dose PPIs; and (3) Level of agreement: A - 84.6%, B - 15.4%. The international consensus group guideline, based on expert opinion, suggested that following the initial 72-hour course of high-dose IV PPI therapy, high-risk patients with bleeding peptic ulcers should continue with oral high-dose PPI therapy, preferably twice daily for the first 14 days. This would effectively maintain acid suppression and lower the chances of rebleeding or surgical intervention[109]. Similarly, the 2021 ACG guideline advised either continuous or intermittent high-dose IV PPI for the initial 3 days after endoscopic hemostasis, followed by twice-daily oral PPI for 2 weeks[85]. Cheng and Sheu[115] reported that extending IV PPI therapy (lower doses) up to 7 days may provide better control of recurrent bleeding episodes in patients with comorbidities. Furthermore, vonoprazan could be used in place of PPIs, as it is found to be non-inferior to high-dose IV PPIs in preventing rebleeding within 30 days following successful endoscopic hemostasis in patients with high-risk peptic ulcers[102]. The panel recommended the use of high-dose oral PPI for 2-4 weeks after 72 hours of IV PPI, as part of acid suppressive therapy in addition to endoscopic management of bleeding peptic ulcers, while also considering PCABs as an alternative to high-dose PPIs.

Acid suppression for H. pylori eradication

Statement 18: For H. pylori eradication, PCAB-based regimens (dual, triple, or bismuth quadruple therapy) are preferred over PPI-based regimens. Standard vonoprazan dosing: 20 mg twice-daily for 10-14 days. Level of agreement: A - 84.6%, B - 15.4%. Vonoprazan-based dual (with amoxicillin) and triple (with amoxicillin and clarithromycin) therapy were reported to be superior to lansoprazole for H. pylori eradication[116]. Vonoprazan-based triple therapy outperformed PPI-based triple therapy with a significant improvement in H. pylori eradication rates[117]. Two-week vonoprazan-based triple therapy outperforms all other regimens, including PPI-based quadruple therapies in terms of eradication rate[118]. Vonoprazan-based quadruple therapy for 10 days or 14 days offers the highest efficacy in H. pylori eradication and is especially recommended in regions with high antibiotic resistance[119]. A comprehensive systematic review and meta-analysis comparing PCABs and PPIs in 8818 patients found that PCAB-based regimens, particularly vonoprazan, showed significantly higher H. pylori eradication rates than PPI-based regimens[120]. Consistent with the literature findings, the panel recommended vonoprazan-based regimens (dual, triple, or bismuth quadruple therapy) over PPI-based regimens for H. pylori eradication. Standard vonoprazan dosing of 20 mg twice-daily for 10-14 days is recommended.

Acid suppression in FD

Active symptoms like bothersome epigastric pain/burning, early satiation, and/or postprandial fullness for three months as per the Rome IV criteria indicate the presence of FD[121]. A full blood count in patients aged ≥ 55 years with dyspepsia, celiac serology in patients with FD and irritable bowel syndrome, and urgent endoscopy in the absence of upper GI alarm symptoms in patients (≥ 55 years) with dyspepsia and weight loss or in patients aged > 40 years with a family history of gastroesophageal cancer were recommended[121]. The panel pointed out that in patients aged > 60 years with dyspepsia symptoms for ≥ 1 month, endoscopy should be prioritized. However, in younger patients, H. pylori testing followed by eradication therapy, and if needed, endoscopy should be done. The suggested diagnosis and treatment algorithm for managing FD[121-123] is given in Figure 4.

Figure 4 Diagnosis and treatment algorithm of functional dyspepsia. H2RA: Histamine-H2 receptor antagonists; PPI: Proton pump inhibitors; H. pylori: Helicobacter pylori.

Statement 19: In patients with symptoms suggestive of FD, acid suppressive therapy should only be offered after investigations and H. pylori testing and eradication. Level of agreement: A - 61.5%, B - 38.5%. H. pylori “test-and-treat” strategy is an increasingly accepted idea for diagnostic-therapeutic approach in patients with FD[124]. H. pylori testing and eradication have been suggested by the 2022 British Society of Gastroenterology guideline for H. pylori-positive patients with FD and empirical acid suppression therapy in patients without H. pylori infection. The guideline further recommended PPIs for their effectiveness and tolerance for the treatment of FD[121]. A PPI- or PCAB-based clarithromycin triple therapy is recommended by the 2024 ACG guideline for patients who remain H. pylori-positive after treatment and if the infection is clarithromycin-sensitive[125]. In patients with PPI-refractory FD, lower-dose vonoprazan (10 mg) showed significant improvement in FD symptoms and quality of life[126]. However, if FD symptoms are not decreased by acid suppressive therapy, then tricyclic antidepressants followed by prokinetics (itopride is preferred) and psychological therapy could be considered[122,123]. The panel recommended that acid suppressive therapy should only be offered after appropriate investigations and after H. pylori testing and eradication in patients with FD symptoms.

Statement 20: Acid suppression in FD can be achieved with H2RAs, PPIs, or PCABs. In patients not responding to PPI or H2RA therapy, PCABs are effective. Level of agreement: A - 46.2%, B - 53.8%. Both PPIs and H2RAs across various doses are more effective than placebo in improving FD symptoms, with standard-dose PPIs ranking highest in treatment efficacy[127]. The 2021 JSGE guideline has suggested the same[128]. Similarly, the 2022 British Society of Gastroenterology guideline affirms that lower-dose PPIs are effective in controlling FD symptoms due to the absence of a clear dose-response relationship. The H2RAs are reported to be well-tolerated and may be an effective option, although the quality of supporting evidence is low[121]. PCABs could be used as an initial therapy for FD, as well as in patients not responding to 8 weeks of conventional PPI therapy[129]. Vonoprazan significantly improved symptoms and quality of life in FD patients unresponsive to PPIs, suggesting that a 10 mg dose could be a viable alternative to PPI[126]. The panel recommended acid suppression in FD using H2RAs, PPIs, or PCABs, with a specific recommendation for PCABs when patients are unresponsive to PPI or H2RA therapy.

APD 360° COMPASS

The panel proposed a comprehensive algorithm (Figure 5) to provide clear guidance for distinguishing the overlapping symptoms of two or more GI disorders. This will help in timely diagnosis and appropriate medical interventions, aiming to reduce morbidity and mortality and significantly improve the patient’s quality of life. The APD 360° compass, by integrating global and Indian clinical guidelines, will support clinicians in making informed, patient-centred decisions, thus enhancing treatment outcomes and helping to reduce the disease burden.

Figure 5 Consensus recommendation on the acid peptic disorders 360° compass^©. PPI: Proton pump inhibitor; PCAB: Potassium-competitive acid blocker; H2RA: Histamine-H2 receptor antagonists; GI: Gastrointestinal; GERD: Gastroesophageal reflux disease; FD: Functional dyspepsia; PUD: Peptic ulcer disease; H. pylori: Helicobacter pylori; OD: Once a day; AMX: Amoxicillin; BD: Twice a day; NSAID: Non-steroidal anti-inflammatory drugs; TID-QID: Three times a day-four times a day; BID: Twice a day; QD: Once a day; BIS: Bismuth; TCA: Tricyclic antidepressant; FLQ: Fluoroquinolone; CBT: Cognitive behavioral therapy; SSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor. In the compass diagram, the innermost circle represents the condition, followed by rings depicting symptoms, alarm symptoms, diagnostic workup, and, in the outermost ring, the preferred treatment options in order of priority, arranged clockwise.

CONCLUSION

In summary, start with once-daily PPIs (or twice-daily/dual-release PPIs) or intermittent/on-demand PCABs (e.g., vonoprazan) for managing typical GERD, and perform therapy de-escalation/discontinuation with caution after personalized risk stratification. The same therapy or bedtime H2RA with PPI is recommended for nocturnal acid breakthrough. In severe erosive esophagitis or complicated GERD, the panel acknowledged vonoprazan’s effectiveness. A gastroenterologist can help in controlling an uncomplicated gastric and duodenal ulcer in case of failed treatment with PPI or PCAB/vonoprazan for 8-12 weeks. Additionally, evaluation and eradication of H. pylori are recommended for patients with a prior history of PUD, currently having NSAID or aspirin use. Vonoprazan 20 mg twice-daily for 10-14 days is recommended over PPI for H. pylori eradication. If PUD exists after 8-12 weeks of standard anti-secretory therapy and H. pylori eradication, or a full course of PPI therapy, doubling the PPI dose or an alternative PPI/PCAB therapy is recommended. In addition to endoscopic management of bleeding peptic ulcers, IV PPI (high-dose PPI is a cost-effective alternative), twice-daily PPI, or oral PCAB (vonoprazan) should be considered. Use of H2RA or PPI for patients with FD is recommended. The PCABs are suggested if the patient is non-responsive to the former therapy.