EPID Research, Espoo, Finland.
AstraZeneca Nordic Baltic, Södertälje, Sweden.
Eur J Clin Pharmacol. 2020 Feb;76(2):257-265. doi: 10.1007/s00228-019-02777-z. Epub 2019 Nov 26.
Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge.
This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type.
In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients.
Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.
在急性冠脉综合征(ACS)患者中,使用口服抗血小板药物(OAPs)对于预防血栓事件至关重要。氯吡格雷、普拉格雷和替格瑞洛的作用可能由于药效学相互作用而增强,但由于它们是 CYP 底物,因此也容易发生药代动力学相互作用。目的是研究 ACS 患者出院后的多药治疗情况。
本项观察性药物利用研究将来自全国登记处的患者水平数据进行了关联。研究人群包括 2009 年至 2013 年期间从芬兰医院出院的成年 ACS 患者。使用逻辑回归模型对药物-药物相互作用的概率进行建模,并对年龄、性别和 ACS 类型等预定预测因素进行比值比分析。
在 54416 例 ACS 患者队列中,91%接受 OAP 治疗的患者使用了氯吡格雷。在接受氯吡格雷治疗的患者中,有 12%在接受氯吡格雷治疗时至少购买过一次华法林。高龄、男性、ST 段抬高型心肌梗死作为首发事件以及既往 ACS 事件史与华法林-OAP 相互作用的风险增加相关(p < 0.001)。布洛芬和曲马多、西酞普兰和艾司西酞普兰等具有药效学相互作用的药物是下一个最常见的引起相互作用的药物。一般来说,已知会引起药代动力学相互作用的药物同时使用的情况很少见,但埃索美拉唑和奥美拉唑在 6%以上接受氯吡格雷治疗的患者中被开具。
华法林和布洛芬是最常使用的引起药效学相互作用并可能增加 OAP 治疗患者出血风险的合并用药。埃索美拉唑和奥美拉唑在接受氯吡格雷治疗的患者中使用,尽管有其他胃保护替代药物。