Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Am J Gastroenterol. 2010 Nov;105(11):2430-6; quiz 2437. doi: 10.1038/ajg.2010.334. Epub 2010 Aug 24.
Recent studies have raised concerns on the clinical effectiveness of clopidogrel when taken in combination with proton pump inhibitors (PPIs), demonstrating an increase in the occurrence of cardiovascular events. In this study, the association between the co-administration of a PPI and clopidogrel and the occurrence of cardiovascular and gastrointestinal (GI) events in a large cohort in the Netherlands was investigated.
A retrospective study was conducted using data from 4 million individuals. New clopidogrel users were identified between January 2006 and December 2007 and followed over time. The Kaplan-Meier method and Cox proportional hazard regression [corrected]analysis were used to calculate the risk of cardiovascular and GI outcomes in clopidogrel patients with or without PPI use.
A total of 18,139 new clopidogrel users were identified; 5,734 subjects (32%) used PPIs concurrently. Patients on PPIs were significantly older, used more co-medications and suffered from more comorbidities. Use of clopidogrel and PPIs was associated with an increased risk of myocardial infarction (hazard ratio (HR) 1.93, 95% confidence interval (CI) 1.40-2.65), unstable angina pectoris (HR 1.79, 95% CI 1.60-2.03), and the composite endpoint (HR 1.75, 95% CI 1.58-1.94) compared with clopidogrel users without PPIs. PPI users also had an increased risk of GI events compared with non-PPI users (HR 4.76, 95% CI 1.18-19.17).
New clopidogrel users on PPIs are at an increased risk of cardiovascular and GI complications compared with those who are not using a PPI. The inferior cardiovascular profile of clopidogrel users on PPIs and the occurrence of channeling bias may be important factors underlying this observation.
最近的研究对氯吡格雷与质子泵抑制剂（PPIs）联合使用的临床疗效提出了担忧，表明心血管事件的发生有所增加。在这项研究中，调查了荷兰一个大型队列中 PPI 联合氯吡格雷的使用与心血管和胃肠道（GI）事件的发生之间的关系。
使用来自 400 万人的数据进行回顾性研究。2006 年 1 月至 2007 年 12 月期间确定新的氯吡格雷使用者，并随时间进行随访。使用 Kaplan-Meier 方法和 Cox 比例风险回归[校正]分析来计算使用或不使用 PPI 的氯吡格雷患者发生心血管和 GI 结局的风险。
共确定了 18139 名新的氯吡格雷使用者；其中 5734 名（32%）患者同时使用了 PPIs。使用 PPI 的患者年龄明显较大，使用更多的合并用药，且患有更多的合并症。与未使用 PPI 的氯吡格雷患者相比，使用氯吡格雷和 PPI 与心肌梗死（风险比（HR）1.93，95%置信区间（CI）1.40-2.65）、不稳定型心绞痛（HR 1.79，95% CI 1.60-2.03）和复合终点（HR 1.75，95% CI 1.58-1.94）的风险增加相关。与非 PPI 使用者相比，PPI 使用者也有发生 GI 事件的风险增加（HR 4.76，95% CI 1.18-19.17）。
与未使用 PPI 的患者相比，使用 PPI 的新氯吡格雷使用者发生心血管和 GI 并发症的风险增加。PPI 使用者的氯吡格雷心血管不良预后和出现的偏倚可能是观察结果的重要因素。
