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Comparative Analysis of Proton Pump Inhibitors (PPIs) vs. Histamine-2 Receptor Blockers (H2RBs)

Introduction to PPIs and H2RBs in Stress Ulcer Prophylaxis

Proton pump inhibitors (PPIs) and histamine-2 receptor blockers (H2RBs) are commonly used medications for stress ulcer prophylaxis, particularly in critically ill patients in intensive care units (ICUs). Both drug classes aim to reduce gastric acid secretion, but they differ in their mechanisms and potential side effects.

Mortality Rates: PPIs vs. H2RBs

Several studies have investigated the impact of PPIs and H2RBs on mortality rates among ICU patients. The PEPTIC trial, a large cluster crossover randomized clinical trial, found that in-hospital mortality was slightly higher in patients receiving PPIs compared to those receiving H2RBs (18.3% vs. 17.5%) 15. This finding was supported by a meta-analysis that suggested PPIs might increase mortality compared to H2RBs, with a pooled relative risk of 1.05 .

Risk of Gastrointestinal Bleeding

While PPIs are more potent in acid suppression, their effectiveness in preventing clinically important gastrointestinal bleeding (CIGIB) compared to H2RBs is debated. A population-based study indicated that H2RBs were associated with a significantly lower risk of CIGIB compared to PPIs . This suggests that despite their stronger acid suppression, PPIs may not offer superior protection against GI bleeding in critically ill patients.

Adverse Effects and Long-term Risks

Dementia Risk

The potential link between the use of PPIs and H2RBs and the risk of dementia has been explored, with mixed results. A meta-analysis concluded that there was no significant difference in dementia risk between users and non-users of PPIs or H2RBs . However, the study recommended cautious use of these medications, particularly in the treatment of Helicobacter pylori.

Kidney Disease

PPIs have been associated with an increased risk of chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). A longitudinal study of US veterans found that PPI users had a higher risk of developing CKD and ESRD compared to H2RB users . This risk was shown to increase with the duration of PPI use.

Pneumonia

In patients with acute stroke, the use of PPIs was linked to a higher risk of pneumonia compared to H2RBs. This was particularly evident in patients with dysphagia and impaired consciousness, where the relative risk of pneumonia was significantly higher for PPI users .

Gut Microbiome Alterations

Both PPIs and H2RBs can alter the gut microbiome, but PPIs have a more pronounced effect. In hemodialysis patients, PPI use was associated with significant changes in gut microbiota composition, including an increase in the Streptococcus genus, which could have clinical implications .

Conclusion

The comparative analysis of PPIs and H2RBs reveals that while both drug classes are effective for stress ulcer prophylaxis, they come with different risk profiles. PPIs may be associated with higher mortality, increased risk of kidney disease, and significant alterations in the gut microbiome. On the other hand, H2RBs appear to have a lower risk of gastrointestinal bleeding and pneumonia in certain patient populations. Clinicians should weigh these risks and benefits when choosing between PPIs and H2RBs for their patients, particularly in critical care settings.

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Most relevant research papers on this topic

A cluster randomised, crossover, registry-embedded clinical trial of proton pump inhibitors versus histamine-2 receptor blockers for ulcer prophylaxis therapy in the intensive care unit (PEPTIC study): study protocol.

The PEPTIC study aims to compare the effect of using proton pump inhibitors (PPIs) as the preferred agent for stress ulcer prophylaxis in mechanically ventilated adults in ICU with using histamine-2 receptor blockers (H2RBs) as the preferred agent on in-hospital mortality.

RCT

2018·

16citations

·P. Young et al.

Proton pump inhibitors vs. histamine-2 receptor antagonists likely increase mortality in critical care: an updated meta-analysis.

Stress ulcer prophylaxis with PPIs likely increases mortality compared to H2RAs in critically ill patients.

Meta-Analysis

2020·

8citations

·Todd C Lee et al.

Possible dementia risk of proton pump inhibitors and H2 receptor blockers use in the treatment of Helicobacter pylori: A meta-analysis study.

Using PPIs or H2-receptor-blockers for Helicobacter pylori treatment is not related to dementia, but careful use and adherence to treatment duration is still recommended.

Meta-Analysis

2020·

6citations

·Yongzhen Zhang et al.

Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans

PPI use is associated with an increased risk of death, particularly among those without gastrointestinal conditions and those with prolonged duration of use.

Observational StudyRigorous JournalHighly Cited

2017·

206citations

Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial.

Preferential use of PPIs for stress ulcer prophylaxis in ICU patients receiving invasive mechanical ventilation reduces in-hospital mortality rates compared to H2RBs.

RCTLarge Human TrialHighly Cited

2020·

140citations

·P. Young et al.

Comparative Effectiveness of Proton Pump Inhibitors vs Histamine Type 2 Receptor Blockers for Preventing Clinically Important Gastrointestinal Bleeding During Intensive Care: A Population‐Based Study

H2Bs are significantly associated with lower clinically important gastrointestinal bleeding risk compared to PPIs in critically ill adults.

Observational Study

2018·

30citations

·C. Lilly et al.

In US veterans, PPIs were linked to increased all-cause and some cause-specific mortality compared with H2-blockers

Proton-pump inhibitors (PPIs) are linked to increased risk of all-cause and some cause-specific mortality in US veterans compared to histamine H2-receptor antagonists (H2-blockers).

Observational StudyRigorous Journal

2019·

0citations

·R. Koretz

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients

Prophylactic acid-suppressive therapy with proton pump inhibitors may need to be avoided in acute stroke patients susceptible to pneumonia.

Observational StudyRigorous Journal

2017·

31citations

·N. Arai et al.

Anti-Acid Drug Treatment Induces Changes in the Gut Microbiome Composition of Hemodialysis Patients

PPIs significantly changed gut microbiota composition in hemodialysis patients compared to H2-blocker users or controls, with a significant increase in Streptococcus genus.

Observational StudyRigorous Journal

2021·

14citations

·Yi-Ting Lin et al.

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

PPI exposure is associated with increased risk of developing chronic kidney disease, CKD progression, and developing ESRD.

Observational StudyHighly Cited

2016·

270citations

·Yan Xie et al.

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