Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents

Farhat, Nawal; Fortin, Yannick; Haddad, Nisrine; Birkett, Nicholas; Mattison, Donald R.; Momoli, Franco; Wen, Shi Wu; Krewski, Daniel

doi:10.1080/10408444.2019.1583167

Cited by 23 publications

(17 citation statements)

References 152 publications

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“…Chronic disruption of eNOS may explain an increased risk for cardiovascular events among long-term users of PPIs, as found in several studies. 1,6 As PPIs play an important role in the treatment of gastric acid-related disorders, more insight into the consequences of long-term intake is desired. Studies that relate new PPI intake with the variation of endothelial function and plasma citrulline levels measured over time could deliver further evidence for PPI-induced DDAH inhibition in humans and explain the potential for increased cardiovascular risk in long-term PPI users.…”

Section: Ta B L Ementioning

confidence: 99%

“…4 One approach to improve the evidence is through testing of plausible biological pathways. Several cohort studies indicated that an increased risk of myocardial infarction and ischemic stroke in PPI users was independent of aspirin or clopidogrel intake, 3,5,6 which suggests an underlying mechanism that does not directly involve either platelet aggregation or change in drug absorption due to a rise in gastric pH. 3,5 As a result, potential biochemical mechanisms were put forward that could explain the effect of PPI intake on the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

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Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross‐sectional study

et al. 2021

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Section: Ta B L Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross‐sectional study

et al. 2021

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“…In particular, no significant differences were observed in the first group, limited to RCTs, and in the third group. A modest positive association was observed in the second group, analysing data from observational studies and RCTs; however, the magnitude of the association was lower when the analysis was restricted to RCTs or propensity score matched studies [76]. TAKE HOME MESSAGE: contrasting evidence suggests that long-term PPIs treatment increases the risk of cardiovascular events, by impairing endothelial function and accelerating endothelial aging.…”

Section: Cardiovascular Riskmentioning

confidence: 99%

Side effects of long-term use of proton pump inhibitors: practical considerations

Castellana¹,

Pecere²,

Furnari³

et al. 2021

Polish Archives of Internal Medicine

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited, distributed under the same license, and used for noncommercial purposes only.

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“…Over the years several reviews and meta-analyses addressed the question of concomitant clopidogrel and PPI treatment arriving at inconsistent conclusions [47,48,[70][71][72][73]. Therefore, the aim of the present study was to examine the interaction between clopidogrel and omeprazole in order to elucidate whether omeprazole reduces the therapeutic efficacy of clopidogrel.…”

Section: Introductionmentioning

confidence: 97%

The Association between Co-Administration of Omeprazole and Clopidogrel and Cardiovascular Outcomes

An¹,

E²,

Gilutz³

et al. 2021

austinjpharmacolther

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Objective: To examine whether co-administration of clopidogrel and omeprazole affects the clinical outcomes of clopidogrel treatment. Design and Methods: A retrospective cross-sectional study of 4078 patients after a percutaneous coronary intervention and stent implantation. Seven hundred twenty-three clopidogrel-treated patients who fulfilled the inclusion criteria of the study were included: 318 treated only with clopidogrel; 405 treated with clopidogrel and omeprazole (study group). The interaction between the drugs was examined in relation to adverse clinical outcomes such as all-cause mortality, Major Adverse Cardiovascular Events (MACE) and cardiac hospitalizations during one year. Results: No significant difference was detected between the groups regarding the primary outcomes of the study. Regression models adjusted to basic characteristics and clinical variables showed a significant association between the study group and the primary outcomes through interactions with specific covariates: “all-cause mortality” through interaction with the covariate ethnicity (not-Jewish) (OR = 43.12, 95% CI 1.19-1567.8, P = 0.04), “MACE” through interaction with the covariates gender (female) and complicated angioplasty (OR= 9.36, 95% CI 2.04-42.94, P= 0.04); and “cardiac hospitalizations” through interaction with the covariates extent of artery stenosis and hypertension (OR= 2.65, 95% CI 1.043-6.76, P = 0.04). Conclusion: Addition of omeprazole to clopidogrel may be associated with increased incidence of negative clinical outcomes, including death and MACE. These findings underscore the need for conduction of prospective randomized controlled trials that will examine the association between addition of omeprazole to clopidogrel and the incidence of clinical outcomes.

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Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents

Cited by 23 publications

References 152 publications

Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross‐sectional study

Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross‐sectional study

Side effects of long-term use of proton pump inhibitors: practical considerations

The Association between Co-Administration of Omeprazole and Clopidogrel and Cardiovascular Outcomes

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