Abrignani Maurizio Giuseppe, Zullo Angelo, Gabrielli Domenico, Milazzo Giuseppe, De Francesco Vincenzo, De Luca Leonardo, Francese Maura, Gatta Luigi, Imazio Massimo, Riccio Elisabetta, Rossini Roberta, Scotto Di Uccio Fortunato, Soncini Marco, Colivicchi Furio, Di Lenarda Andrea, Gulizia Michele Massimo, Monica Fabio
U.O.C. Cardiologia, P.O. S. Antonio Abate, ASP Trapani, Erice (TP).
U.O.C. Gastroenterologia, Ospedale Nuovo Regina Margherita, Roma.
G Ital Cardiol (Rome). 2020 Mar;21(3):228-241. doi: 10.1714/3306.32772.
Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like traditional anticoagulants, novel oral anticoagulants may cause gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of gastrointestinal bleeding as compared with warfarin. However, the usefulness of PPIs in patients receiving these anticoagulants deserves to be further demonstrated. Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.
阿司匹林和P2Y12受体拮抗剂广泛应用于心血管和脑血管疾病领域。胃肠道并发症，包括溃疡和出血，在抗血小板治疗期间相对常见，因此，常开具质子泵抑制剂（PPI）进行联合治疗。然而，有研究提示PPI可能会增加心血管事件的风险，近年来，人们一直在讨论这些药物是否会降低阿司匹林甚至氯吡格雷的心血管保护作用。事实上，药效学和药代动力学研究表明，PPI与氯吡格雷之间通过CYP2C19存在相互作用，这可能导致临床无效，进而导致心血管事件发生率升高。美国食品药品监督管理局和欧洲药品管理局在2010年发出警告，不鼓励氯吡格雷与奥美拉唑或埃索美拉唑联合使用。此外，PPI的使用是否会影响新型P2Y12受体拮抗剂替格瑞洛和普拉格雷的临床疗效，目前尚不清楚。根据现行指南，对于有胃肠道出血危险因素的患者，包括高龄、同时使用抗凝剂、类固醇或非甾体抗炎药以及幽门螺杆菌感染，建议将PPI与抗血小板治疗联合使用。与传统抗凝剂一样，新型口服抗凝剂也可能导致胃肠道出血。随机临床试验和观察性研究的结果均表明，与华法林相比，高剂量达比加群（150mg，每日两次）、利伐沙班和高剂量依度沙班（60mg，每日一次）发生胃肠道出血的风险更高。然而，PPI在接受这些抗凝剂治疗的患者中的有效性仍有待进一步证实。鉴于接受抗血栓药物和PPI治疗患者数量众多，即使血小板抑制或抗凝作用略有降低，也可能产生相当大的临床影响。意大利心脏病学和血管医学协会（ANMCO）和意大利胃肠病学和消化内镜学会（AIGO）的这份联合声明总结了目前关于血小板抑制剂、抗凝剂和PPI联合广泛使用的知识。此外，它概述了支持或反对这些药物之间药物相互作用的证据，并讨论了相应的临床意义。
