Why the study?
Clopidogrel and PPIs both exploit CYP2C19, potentially leading to inadequate antiplatelet response and severe cardiovascular events when coprescribed to prevent GI bleeding.
Does the addition of proton pump inhibitors to clopidogrel increase the risk of major adverse cardiovascular events in post-PCI patients?
Does the addition of proton pump inhibitors to clopidogrel increase the risk of major adverse cardiovascular events in post-PCI patients?
Concomitant use of proton pump inhibitors and clopidogrel in post-PCI patients is associated with an increased risk of adverse cardiovascular events without a significant reduction in bleeding risk.
Warrants caution against routine PPI-clopidogrel co-use post-PCI due to higher ischemic risk without bleeding benefit; confirms interaction and supports dedicated RCTs.
Background and Aim: Proton Pump Inhibitors (PPIs) are frequently advised to cardiac patients as part of their polypharmacy regimen to reduce gastrointestinal bleeding. Clopidogrel and PPIs are both prodrugs that exploit the cytochrome P450 enzyme system, notably P450 (CYP2C19) leading to inadequate antiplatelet action in response to clopidogrel which may potentially lead to severe cardiovascular events. Methods: We conducted a meta-analysis study which included papers from EMBASE, WOS, PubMed, The Cochrane Library, and The Chinese Biomedical Medical Literature Database that were published up to December 2019. The Cochrane Review Manual 5.0.2 criteria were used to assess the studies’ quality. The complete statistical study was carried out using the RStudio package version 1.3.1073. The assumption of heterogeneity was tested using a chi-square test based on a Q-test. Results: We selected 16 studies with 61,835 patients for our metaanalysis, comprising 33,964 non-PPI patients and 27,871 PPI patients who also took clopidogrel. Forest plots were built for each of the outcomes to gather the results. Conclusion: According to the study, individuals who had PPI and clopidogrel had an increased risk of major adverse cardiovascular events (MACE), MI recurrence, stent thrombosis, and stroke. As with bleeding, there is no statistical significance, indicating that the two groups are equivalent. Several peer-reviewed studies contradicted these conclusions. Major Findings: 1. Patients consuming proton pump inhibitors and clopidogrel after PCI exhibited higher risk of major adverse cardiovascular events, myocardial infarction recurrence, stent thrombosis and stroke. 2. PPIs inhibit CYP2C19 enzyme which is crucial for clopidogrel activation. This interaction reduces clopidogrel’s anti platelet efficacy resulting in positive cardiovascular events. 3. No statistical difference for bleeding risk in post PCI patients consuming clopidogrel with or without PPI.
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Khan et al. (2024) studied this question.
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