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

Muzamil Khawaja, Janki Thakker, Riyad Kherallah, Masafumi Kitakaze, Hani Jneid, Dominick J. Angiolillo, Yochai Birnbaum

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
JournalCardiovascular Drugs and Therapy
StateAccepted/In press - 2022
Externally publishedYes


  • Congestive heart failure
  • Coronary artery disease
  • Dual antiplatelet therapy
  • Gastrointestinal bleeding
  • H receptor antagonists
  • Proton pump inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)


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