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台湾急性冠状动脉综合征患者联合使用氯吡格雷和质子泵抑制剂与心血管结局的关系。

Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan.

机构信息

School of Pharmacy Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Taipei, Taiwan.

出版信息

Br J Clin Pharmacol. 2012 Nov;74(5):824-34. doi: 10.1111/j.1365-2125.2012.04250.x.

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Conflicting results have been reported regarding the increased risk of adverse outcomes in the concomitant use of clopidogrel and proton pump inhibitors (PPIs) compared with the use of clopidogrel alone.

WHAT THIS STUDY ADDS

Our study indicated no statistically significant increase in the risk of rehospitalization for acute coronary syndrome due to concurrent use of clopidogrel and PPIs in an Asian population with higher prevalence of CYP2C19 intermediate and poor metabolizers. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for acute coronary syndrome. AIMS Our study aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs) with clopidogrel on the cardiovascular outcomes of patients with acute coronary syndrome (ACS). Furthermore, we sought to quantify the effects of five individual PPIs when used concomitantly with clopidogrel.

METHODS

We conducted a retrospective cohort study of patients who were newly hospitalized for ACS between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel (n= 37 099) during the follow-up period. A propensity score technique was used to establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary clinical outcome was rehospitalization for ACS, while secondary outcomes were rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with stent, PTCA without stent and revascularization (PTCA or coronary artery bypass graft surgery) after the discharge date for the index ACS event.

RESULTS

The adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence interval, 0.971-1.139; P= 0.214) in the propensity score matched cohort. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for ACS (adjusted hazard ratio, 1.226; 95% confidence interval, 1.066-1.410; P= 0.004). Concomitant use of esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the risk.

CONCLUSIONS

Our study indicated no statistically significant increase in the risk of rehospitalization for ACS due to concurrent use of clopidogrel and PPIs overall. Among individual PPIs, only omeprazole was found to be statistically significantly associated with increased risk of rehospitalization for ACS.

摘要

关于这一主题已知的情况

与单独使用氯吡格雷相比,氯吡格雷联合质子泵抑制剂(PPIs)使用与不良结局风险增加相关的结果存在冲突。

本研究的新增内容

我们的研究表明,在 CYP2C19 中间代谢和弱代谢者患病率较高的亚洲人群中,氯吡格雷联合 PPIs 使用与因急性冠状动脉综合征(ACS)再住院的风险无统计学显著增加。在所有的 PPIs 中,仅发现奥美拉唑与因 ACS 再住院的风险增加有统计学显著相关性。

目的

本研究旨在研究质子泵抑制剂(PPIs)与氯吡格雷联合使用对急性冠状动脉综合征(ACS)患者心血管结局的影响。此外,我们试图量化五种单独的 PPI 在与氯吡格雷联合使用时的影响。

方法

我们对 2006 年 1 月 1 日至 2007 年 12 月 31 日期间从台湾全民健康保险研究数据库(NHIRD)中检索到的新住院的 ACS 患者进行了回顾性队列研究,在随访期间他们被开氯吡格雷处方(n=37099)。使用倾向评分技术以 1:1 的比例建立匹配队列(每组 5173 例)。主要临床结局是因 ACS 再住院,次要结局是出院后索引 ACS 事件的经皮腔内冠状动脉成形术(PTCA)伴支架、PTCA 无支架和血运重建(PTCA 或冠状动脉旁路移植术)的再住院。

结果

在倾向评分匹配的队列中,因 ACS 再住院的调整后的危险比为 1.052(95%置信区间,0.971-1.139;P=0.214)。在所有的 PPIs 中,仅发现奥美拉唑与 ACS 再住院的风险增加有统计学显著相关性(调整后的危险比,1.226;95%置信区间,1.066-1.410;P=0.004)。埃索美拉唑、泮托拉唑、雷贝拉唑和兰索拉唑的联合使用并未增加风险。

结论

我们的研究表明,总体而言,氯吡格雷联合 PPIs 使用与 ACS 再住院风险无统计学显著增加。在单独的 PPIs 中,仅发现奥美拉唑与 ACS 再住院风险增加有统计学显著相关性。

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