Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel

Li, Shuai; Liu, Fuwei; Chen, Chen; Zhu, Wenzhen; Ma, Jianyong; Hu, Jinzhu; Xu, Jiahua; Hong, Kui

doi:10.1536/ihj.18-584

Cited by 20 publications

(17 citation statements)

References 39 publications

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“…In total, we identified 6241 articles, scrutinised 375 full‐text articles, and included 132 eligible articles (3.52%) for preliminary data extraction ( Figure S1). After the selection criteria for the overlapping meta‐analyses were applied, 61 articles were ultimately selected for evidence synthesis 6–8,31–88 . Agreement between reviewers for eligibility of articles was excellent (κ statistic = 0.8).…”

Section: Resultsmentioning

confidence: 99%

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Veettil

Sadoyu²,

Bald

et al. 2021

Brit J Clinical Pharma

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The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.Methods: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.

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Section: Resultsmentioning

confidence: 99%

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Veettil

Sadoyu²,

Bald

et al. 2021

Brit J Clinical Pharma

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“…Our study adds information to the safety evaluation of PPIs. Large and well‐controlled cohort studies had linked PPI use to an increased risk of MI and IS, 2–6 but more recently these concerns have been attenuated. In a large study using administrative claims data from commercial and Medicare Supplemental plans, researchers found no increase in risk of primary MI during PPI intake of up to 3 years 12 .…”

Section: Discussionmentioning

confidence: 99%

“…For more than a decade, PPIs have also been sold over‐the‐counter and are often consumed without medical supervision. The long‐term risk of PPI intake has received considerable attention in recent years, with large and well‐controlled cohort studies linking PPI use to an increased risk of myocardial infarction (MI), ischaemic stroke (IS) 2‐6 and cardiovascular death 7 . The elevated risk was associated with PPI use but not with the use of H 2 ‐receptor antagonists (H 2 RAs), the most commonly used alternative class of medications to treat acid‐related gastrointestinal conditions 8 .…”

Section: Introductionmentioning

confidence: 99%

The long‐term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008‐2018)

Nolde

Ahn

Dreischulte

et al. 2021

Aliment Pharmacol Ther

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Summary Background Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long‐term cardiovascular risk in observational studies. Aims To evaluate long‐term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2‐receptor antagonist (H2RA) therapy in adults without pre‐existing cardiovascular or cerebrovascular disease Methods Using administrative claims data (2008–2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan‐Meier estimators. Results We identified 1 143 948 new users of PPIs and 36 229 new users of H2RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow‐up time was 6.2 years for PPI initiators and 5.3 years for H2RA initiators. After 10 years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80‐1.16) and 0.98 (95% CI: 0.89‐1.08), respectively. Conclusions This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.

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“…The present systematic review also assessed the safety of PPIs independent of clopidogrel use and found that the use of PPIs was not associated with increased risks of MACEs or all-cause mortality. This finding is significant because previous studies have questioned whether there exists a potential association between PPI use and adverse ischemic events directly conferred by PPIs (Shah et al, 2015;Wang et al, 2017;Li et al, 2019). To date, several pathophysiological hypotheses have been proposed (Wilhelm et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

Guo

Huang

2021

Front. Pharmacol.

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Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

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Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel

Cited by 20 publications

References 39 publications

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

The long‐term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008‐2018)

Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

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