PPIs Are Not Responsible for Elevating Cardiovascular Risk in Patients on Clopidogrel—A Systematic Review and Meta-Analysis

Frontiers in Physiology

Dániel Pécsi¹  Katalin Márta¹  Zsolt Szakács¹  Alexandra Mikó¹  Péter Hegyi²  Tamás Lantos³  Alexandra Demcsák⁴  Zoltán Gyöngyi⁵  László Czopf⁶  Áron Vincze⁷  Judit Bajor⁷  Imre László Szabó⁷  Hussain Alizadeh⁸  Emese Réka Bálint⁹  Petra Hartmann^1,11 

[1] 0János Szentágothai Research Centre, University of Pécs, Pécs, Hungary;1Momentum Translational Gastroenterology Research Group, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary;Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary;Department of Pediatrics and Pediatric Health Centre, University of Szeged, Szeged, Hungary;Department of Public Health Medicine, University of Pécs Medical School, Pécs, Hungary;Division of Cardiology, First Department of Internal Medicine, University of Pécs Medical School, Pécs, Hungary;Division of Gastroenterology, First Department of Internal Medicine, University of Pécs Medical School, Pécs, Hungary;Division of Hematology, First Department of Internal Medicine, University of Pécs Medical School, Pécs, Hungary;First Department of Internal Medicine, University of Szeged, Szeged, Hungary;Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary;Institute of Surgical Research, University of Szeged, Szeged, Hungary;

关键词: proton pump inhibitors;    clopidogrel;    cardiovascular risk;    drug interaction;    cytochrome P450;    meta-analysis;   

DOI  :  10.3389/fphys.2018.01550

来源: DOAJ

【 摘 要 】

Background: Clopidogrel and proton pump inhibitors (PPIs) are metabolized by cytochrome P450 enzymes. Contradictory results have been reported on possible complications of simultaneous PPI and clopidogrel use. Our aim was to investigate the clinical relevance of this debate with a systematic review and meta-analysis.Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials electronic databases were searched for human studies [randomized controlled trials (RCTs) and observational studies] using the PICO format (P: patients on clopidogrel; I: patients treated with PPI; C: patients without PPI treatment; O: cardiovascular risk). We screened eligible studies from 2009 to 2016. After study exclusions, we extracted data from 27 articles for three outcomes: major adverse cardiac event (MACE), myocardial infarction (MI) and cardiovascular (CV) death. The meta-analysis was registered on PROSPERO (CRD42017054316).Results: Data were extracted on 156,823 patients from the 27 trials included (MACE: 23, CV death: 10, MI: 14). The risks of MACE (RR = 1.22, 95% CI = 1.06–1.396, p = 0.004) and MI (RR = 1.43, 95% CI = 1.24–1.66, p < 0.001) were significantly higher in the PPI plus clopidogrel group. However, subgroup analysis demonstrated that this significance disappeared in RCTs (RR = 0.99, 95% CI = 0.76–1.28, p = 0.93) in the MACE outcome group. There was no effect of combined PPI and clopidogrel therapy on CV death outcome (RR = 1.21, 95% CI = 0.97–1.50, p = 0.09).Conclusion: Concomitant use of PPIs and clopidogrel has been proved not to be associated with elevated cardiovascular risks according to RCTs. Based on our results, no restrictions should be applied whenever PPIs and clopidogrel are administered simultaneously.

【 授权许可】

Unknown