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Antacid Therapy in Coronary Artery Disease and Heart Failure: Proton Pump Inhibitors vs. H2 Receptor Blockers

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Abstract

Purpose

Acid suppressive therapy using histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) can be utilized for the prevention of gastrointestinal bleeding (GIB) among patients with cardiovascular disease receiving dual antiplatelet therapy (DAPT). However, emerging data suggests underlying associations between PPI or H2RA use and cardiovascular disease incidence, progression, and mortality. This review explores the history of acid suppressive therapies and their use in cardiovascular disease patients and the growing evidence in support of H2RA use.

Recent Findings

PPIs were originally championed as better than H2RAs for preventing GIB events in cardiovascular disease patients on DAPT therapy, but there is evidence to suggest that drug-drug interactions between clopidogrel and PPIs may translate to worse cardiovascular outcomes. Studies demonstrating PPI superiority in the setting of DAPT were also limited due to small sample sizes and high levels of bias. Consequently, there is renewed interest in H2RAs for patients on DAPT with some data demonstrating similar or improved clinical outcomes over PPI therapy. Additionally, studies have discovered a possible role for H2RAs in the management of heart failure (HF) incidence, symptoms, and mortality.

Summary

Studies comparing H2RAs and PPIs in patients on DAPT have demonstrated mixed results for cardiovascular and GIB outcomes, with several studies being underpowered and limited by biases. Recent clinical and pre-clinical studies now support the noninferiority of H2RAs for major outcomes and even utility in HF. These findings suggest that H2RAs may warrant reconsideration as an acid suppressive therapy over PPIs for patients on DAPT or with HF.

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Data Availability

Original research data will be available upon request.

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Funding

This work was funded by the John S. Dunn Chair in Cardiology Research and Education.

Author information

Authors and Affiliations

  1. The Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Muzamil Khawaja, Janki Thakker & Riyad Kherallah

  2. Center of Medical Innovation and Translational Research, Department of Medical Data Science, Osaka University Graduate School of Medicine, Osaka, Japan

    Masafumi Kitakaze

  3. The Section of Cardiology, The Department of Medicine, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX, 77030, USA

    Hani Jneid & Yochai Birnbaum

  4. Division of Cardiology, The University of Florida College of Medicine, Jacksonville, FL, USA

    Dominick J. Angiolillo

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  1. Muzamil Khawaja
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Contributions

All authors contributed to the manuscript. Dr. Yochai Birnbaum had the idea for the article and authors Muzamil Khawaja, Janki Thakker, and Riyad Kherallah all performed the literature search and drafted the work. All authors commented and revised previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yochai Birnbaum.

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All authors read and approved the final manuscript, submitted for consideration of publication in Cardiovascular Drugs and Therapy.

Conflict of Interest

Hani Jneid: no relevant financial or non-financial interests to disclose.

Masafumi Kitakaze: research grant from Takeda; speaker honoraria from AstraZeneca, Ono, Novartis, Tanabe-Mitsubishi, Takeda, Pfizer, Daiichi-Sankyo, Otsuka, Sanofi, Boehringer Ingelheim, Amgen, Kowa, Toyama-Kagaku, and Kureha.

Dominick J. Angiolillo: consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work. He also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation.

Yochai Birnbaum: research grant from AstraZeneca.

Muzamil Khawaja: no relevant financial or non-financial interests to disclose.

Janki Thakker: no relevant financial or non-financial interests to disclose.

Riyad Kherallah: no relevant financial or non-financial interests to disclose.

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Khawaja, M., Thakker, J., Kherallah, R. et al. Antacid Therapy in Coronary Artery Disease and Heart Failure: Proton Pump Inhibitors vs. H2 Receptor Blockers. Cardiovasc Drugs Ther 38, 181–189 (2024). https://doi.org/10.1007/s10557-022-07358-4

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