Why the study?
Proton pump inhibitors may reduce clopidogrel availability by competitive antagonism, potentially increasing ischemic events after PCI.
Does proton pump inhibitor use increase adverse cardiovascular events in patients on aspirin and clopidogrel following percutaneous coronary intervention?
Cohort (n=4,635)
Does proton pump inhibitor use increase adverse cardiovascular events in patients on aspirin and clopidogrel following percutaneous coronary intervention?
Answers are grounded in this paper and cite their sources.
In patients on clopidogrel and aspirin after PCI, concomitant PPI use is associated with a higher risk of 2-year MACE and NACE, driven primarily by target lesion revascularization, without an increase in bleeding.
BACKGROUND: Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events. METHODS: We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation. RESULTS: The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51). CONCLUSIONS: In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT.
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Chandrasekhar et al. (2016) conducted a cohort in Coronary stenting on dual antiplatelet therapy (n=4,635). Proton pump inhibitors (PPI) vs. Non-users was evaluated on Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR) (HR 1.27, 95% CI 1.04-1.55).
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