Radboud University Nijmegen Medical Center, Department of Cardiology, Nijmegen, The Netherlands.
Heart. 2013 Apr;99(8):520-7. doi: 10.1136/heartjnl-2012-302371. Epub 2012 Jul 31.
Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue.
Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome.
PubMed, Web-of-Science, Cochrane Database and reference lists of related articles.
Published articles on controlled studies addressing the addition of PPIs to clopidogrel. Platelet function studies describe patients as well as healthy volunteers. Clinical studies concern patients using clopidogrel for acute coronary syndromes or because of stent implantation for stable coronary disease.
Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data.
In 70% (7/10) of the laboratory studies examining healthy volunteers on clopidogrel, addition of PPIs resulted in a significant reduction in platelet inhibition. For patients, this was observed in 11/18 (61%) studies. The 33 clinical studies showed significant heterogeneity in observed outcomes, with risk ratios for major adverse cardiovascular events varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in only two studies. Consequently, imbalances between prognosticators at baseline and PPI prescription bias markedly contributed to the variability in results.
Despite indications of reduced antiplatelet activity ex vivo in the case of PPI administration in clopidogrel users, data on the clinical consequences are controversial. With the accumulating evidence from better designed, prospective clinical studies, an adverse effect of PPI use on clinical outcome in patients on clopidogrel cannot be substantiated. This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data.
氯吡格雷与阿司匹林联合应用可改善急性冠脉综合征患者的预后，但实验室研究表明，质子泵抑制剂（PPIs）联合应用时会降低抗血小板作用。尽管回顾性研究提供了佐证数据，但新的临床数据加剧了这一问题的争议。
系统评价 PPI 联合氯吡格雷对血小板功能和心血管结局的影响。
PubMed、Web-of-Science、Cochrane 数据库和相关文章的参考文献列表。
发表的关于氯吡格雷联合应用 PPI 的对照研究文章。血小板功能研究描述了患者和健康志愿者。临床研究涉及因急性冠脉综合征或因稳定型冠状动脉疾病植入支架而使用氯吡格雷的患者。
两名研究者独立审查了入选文章的资格，并由一名作者提取数据。
在 70%（10 篇中的 7 篇）研究氯吡格雷健康志愿者的实验室研究中，联合应用 PPI 导致血小板抑制显著降低。在患者中，有 11/18（61%）的研究观察到这种情况。33 项临床研究显示观察结果存在显著异质性，在随机分配使用 PPI 的情况下，主要不良心血管事件的风险比从 0.64 到 4.58 不等。因此，基线预后因素的不平衡和 PPI 处方偏倚极大地导致了结果的变异性。
尽管在氯吡格雷使用者中给予 PPI 会导致体外抗血小板活性降低的迹象，但关于临床后果的数据仍存在争议。随着更好设计、前瞻性临床研究的积累证据，不能证实 PPI 使用对氯吡格雷患者临床结局的不良影响。本综述对基于主要为非随机数据的定量分析得出的结论的有效性提出了质疑。
