Sridharan Kannan
Department of Pharmacology &p Therapeutics, College of Medicine & Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
Curr Cardiol Rev. 2025 May 12. doi: 10.2174/011573403X374906250417043907.
The aim of this study is to evaluate the safety profiles of antiplatelet-proton pump inhibitors (PPIs) combinations and assess the clinical implications of their concurrent use in real-world settings through pharmacovigilance data analysis.
The concomitant use of PPIs with antiplatelet therapy remains controversial due to potential drug interactions affecting clinical outcomes. While PPIs are recommended for gastroprotection in patients receiving antiplatelet therapy, concerns persist regarding their impact on antiplatelet efficacy, particularly with dual antiplatelet therapy (DAPT).
The objective of this study is to analyze and compare the thrombo-embolic risk profiles of various antiplatelet-PPI combinations using the FDA Adverse Event Reporting System database.
We conducted a comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database to evaluate the thrombo-embolic risk associated with antiplatelet-PPI combinations. The reporting odds ratio (ROR) and information component were calculated to detect safety signals. The interaction signal score (INTSS) was used to assess the protective or harmful effects of adding acetylsalicylic acid to clopidogrel-PPI combinations.
Analysis revealed significant safety signals for thrombo-embolic events with clopidogrel-rabeprazole (ROR: 62.67, 95% CI: 38.38-102.32) and clopidogrel-omeprazole (ROR: 6.87, 95% CI: 4.89-9.66) combinations. DAPT-PPI combinations showed comparable safety profiles to monotherapy-PPI combinations. The INTSS analysis suggested a potential protective effect of acetylsalicylic acid when added to clopidogrel-PPI combinations. Genderspecific analysis revealed female predominance in monotherapy complications and male predominance in combination therapy events. Clinical outcomes, including mortality and hospitalization rates, were comparable between groups.
This pharmacovigilance analysis suggests that while DAPT-PPI combinations demonstrate acceptable safety profiles, careful consideration should be given to PPI selection, particularly given the unexpected safety signals with rabeprazole and confirmed risks with omeprazole. The addition of acetylsalicylic acid to clopidogrel-PPI combinations may offer protective effects against thrombo-embolic events. These findings support individualized riskbenefit assessment in selecting antiplatelet-PPI combinations while ensuring adequate gastroprotection for high-risk patients.
本研究旨在评估抗血小板药物与质子泵抑制剂（PPI）联合使用的安全性概况，并通过药物警戒数据分析评估其在现实环境中同时使用的临床意义。
由于潜在的药物相互作用会影响临床结果，PPI与抗血小板治疗同时使用仍存在争议。虽然推荐在接受抗血小板治疗的患者中使用PPI进行胃保护，但人们仍担心其对抗血小板疗效的影响，尤其是在双联抗血小板治疗（DAPT）中。
本研究的目的是使用美国食品药品监督管理局（FDA）不良事件报告系统数据库分析和比较各种抗血小板-PPI联合用药的血栓栓塞风险概况。
我们对FDA不良事件报告系统（FAERS）数据库进行了全面分析，以评估与抗血小板-PPI联合用药相关的血栓栓塞风险。计算报告比值比（ROR）和信息成分以检测安全信号。使用相互作用信号评分（INTSS）评估在氯吡格雷-PPI联合用药中添加阿司匹林的保护或有害作用。
分析显示，氯吡格雷-雷贝拉唑（ROR：62.67，95%置信区间：38.38-102.32）和氯吡格雷-奥美拉唑（ROR：6.87，95%置信区间：4.89-9.66）联合用药存在血栓栓塞事件的显著安全信号。DAPT-PPI联合用药的安全性概况与单药-PPI联合用药相当。INTSS分析表明，在氯吡格雷-PPI联合用药中添加阿司匹林可能具有潜在的保护作用。性别特异性分析显示，单药治疗并发症以女性为主，联合治疗事件以男性为主。各组之间的临床结局，包括死亡率和住院率，具有可比性。
这项药物警戒分析表明，虽然DAPT-PPI联合用药显示出可接受的安全性概况，但应谨慎选择PPI，特别是考虑到雷贝拉唑意外的安全信号和奥美拉唑已证实的风险。在氯吡格雷-PPI联合用药中添加阿司匹林可能对血栓栓塞事件具有保护作用。这些发现支持在选择抗血小板-PPI联合用药时进行个体化的风险效益评估，同时确保为高危患者提供充分的胃保护。
