Key result
Proton pump inhibitor use is linked to ~22% higher MACE risk independent of clopidogrel therapy.
Why the study?
Cerebro-cardiovascular outcomes associated with proton pump inhibitor use in the absence of clopidogrel therapy remain controversial.
Does proton pump inhibitor use increase the risk of cerebro-cardiovascular outcomes independent of clopidogrel?
Meta-Analysis
Does proton pump inhibitor use increase the risk of cerebro-cardiovascular outcomes independent of clopidogrel?
Effect estimate: OR 1.22 (95% CI 1.05-1.40)
p-value: p=0.007
PPI use is associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel use, suggesting greater caution should be exercised when considering their clinical benefits.
May warrant caution with PPI use beyond clopidogrel concerns; extends observational meta-analytic links to cardiovascular risk.
Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.
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Li et al. (2019) conducted a meta-analysis in Cerebro-cardiovascular outcomes. Proton pump inhibitors vs. Non-PPI users was evaluated on Major adverse cardiovascular events (MACEs) (OR 1.22, 95% CI 1.05-1.40, p=0.007). Proton pump inhibitor use was associated with a 22% increased risk of major adverse cardiovascular events (OR 1.22) compared to non-use, independent of clopidogrel therapy.
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