Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses

Abstract

Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual metaanalyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.

Histamine H2 receptor antagonist exhibited comparable all-cause mortality-decreasing effect as β-blockers in critically ill patients with heart failure: a cohort study

“…In this regard, H2RAs may have certain advantages over β-blockers. An important point is that most H2RAs are over-the-counter drugs in most countries with relatively low market price and moderately safe profile according to our previous evidence-based analysis ( Meng et al, 2023 ), which provided a much safer potential treatment strategy for HF as compared with β-blockers especially considering that most chronic HF patients need long-term or even lifelong medication. Furthermore, although it is well acknowledged that β-blockers have good curative effect for patients with HFrEF, little evidence supports the benefits of β-blockers in HF with preserved ejection fraction (HFpEF) ( Cleland et al, 2018 ; Meyer and Lewinter, 2019 ; Brinker et al, 2021 ).…”

“…For several decades, it has long been suggested that histamine H2 receptor (H2R) was highly related to occurrence and development of HF and, as a result, might be a novel promising anti-HF target ( Hara et al, 2002 ; Leary et al, 2014 ; Leary et al, 2016 ; Saheera et al, 2022 ). In this regard, the anti-HF effects of histamine H2 receptor antagonists (H2RAs) consequently gained particular attention in the following related clinical investigations, based on which it was suggested that H2RAs had beneficial effects on short- and medium-term outcomes of HF patients ( Adelborg et al, 2018 ; Zhang et al, 2018 ; Huang et al, 2022 ) and exhibited relatively safe profile in cardiovascular system ( Meng et al, 2023 ). Nevertheless, these findings also raised another key question that whether the use of H2RAs has considerable treatment value as compared with other traditional anti-HF drugs, elucidating of which will eventually provide further evidence to promote the clinical application of H2RAs in treatment of HF.…”