Potent Acid Suppression with PPIs and P-CABs: What’s New?


Purpose of the review

Acid suppression treatment has revolutionized the management of the acid-related disorders since the introduction of the H2-receptor antagonists (H2-RAs) and the proton pump inhibitors (PPIs). However, there has been increasing identification of needs for improvement in antisecretory therapy, especially in gastroesophageal reflux disease (GERD), the eradication of Helicobacter pylori (H. pylori), protection from aspirin (ASA) and non-steroidal inflammatory drug (NSAID) injury and the management of upper gastrointestinal (UGI) bleeding. There have also been increasing publications addressing safety concerns of antisecretory drugs.

Recent findings

The needs have been identified as shortcomings of the pharmacology of the delayed release-PPIs (DR-PPIs), which have short plasma half-lives, required to be given before a meal and show poor control of nocturnal acid secretion. New-generation PPIs have been developed, including dexlansoprazole modified release (MR), instant release omeprazole (IR-omeprazole), while metered release preparations such as Durasec™ or novel molecules such as tenatoprazole have also been developed and achieve superior control of intragastric pH especially at night. The major advance has been the development of the potassium channel acid blocking drugs, which block the K+,H+-ATPase K+ channel, are food independent, reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan, the first P-CAB, has so far been introduced only into a small number of Asian countries. Safety issues have been extensively addressed in numerous publications. This review sets the needs, individual new drug classes and key individual new treatments into clinical context.


Acid suppression treatment is reviewed including the pharmacology, the unmet clinical needs across the acid-related disorders, the place of new drug treatments, and where superiority exists. The safety of antisecretory drugs is broadly summarized with reference to several recent comprehensive reviews and set within the clinical context of patient management, particularly those on long-term treatment who are the greatest risk of some adverse events.

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Fig. 1

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Both authors designed the flow chart and methodology of the paper. Each of them carried out an independent systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were discussed and distilled, paying more attention to systematic reviews and meta-analyses (where available). Each author then wrote given sections, amended by the other co-author. The final manuscript was then prepared, revised critically, and approved before its submission,

Corresponding author

Correspondence to Richard H. Hunt MB, FRCP, FRCP(C).

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Conflict of Interest

Carmelo Scarpignato has served as a speaker, consultant and/or advisory board member for Alfasigma, Pfizer, Takeda, Reckitt-Benkiser and Shionogi, and has, in the past, received funding from Giuliani Pharmaceuticals and Pfizer. Richard H Hunt has served as a speaker, a consultant, and an advisory board member for AstraZeneca, Danone, GSK, Merck, Pfizer, and Takeda.

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This article does not contain (but only mention) any specific studies with human or animal subjects performed by any of the authors.

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Hunt, R.H., Scarpignato, C. Potent Acid Suppression with PPIs and P-CABs: What’s New?. Curr Treat Options Gastro 16, 570–590 (2018). https://doi.org/10.1007/s11938-018-0206-y

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  • Acid suppression
  • PPIs
  • P-CABs
  • GERD
  • H. pylori infection
  • NSAID gastropathy
  • Upper GI bleeding
  • Adverse events