Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy.
Dipartimento Cardio neuro vascolare, Azienda USL Toscana Sud-est, Ospedale di Grosseto, Grosseto, Italy.
Trials. 2020 Feb 17;21(1):192. doi: 10.1186/s13063-020-4116-7.
Ticagrelor is a reversibly binding, direct-acting, oral, PY antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction.
To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart.
Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes.
EudraCT No. 2016-004746-28. No. NCT02701140. TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019.
Fondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.
替格瑞洛是一种可逆结合的、直接作用的、口服的、嘌呤能受体拮抗剂，用于预防冠状动脉疾病（CAD）患者的动脉血栓栓塞事件。替格瑞洛通过抑制红细胞和血小板上的平衡核苷转运蛋白 1（ENT-1）来阻断腺苷再摄取，从而促进腺苷诱导的生理反应，如增加冠状动脉血流速度。同时，腺苷通过激活 A1 受体在触发缺血预适应中发挥重要作用。因此，替格瑞洛增强的腺苷生物利用度的增加可能通过与预适应激活和改善冠状动脉微血管功能相关的机制产生有益的影响。
为了确定替格瑞洛是否可以触发缺血预适应并影响微血管功能，我们设计了这项前瞻性、开放标签、试点研究，纳入了需要分期进行、基于分数血流储备（FFR）指导的经皮冠状动脉介入治疗（PCI）的稳定多血管 CAD 患者。参与者将按 1:1 的比例随机分为替格瑞洛（负荷剂量（LD）180mg，维持剂量（MD）90mg，bid）或氯吡格雷（LD 600mg，MD 75mg）组，在计划进行 PCI 前 3-1 天服用。PCI 操作者将对随机分组情况设盲。主要终点是在罪犯血管的两步序贯冠状动脉球囊充气过程中，通过冠状动脉内心电图（ECG）评估的 ST 段抬高差值（以毫米计，mm）。次要终点是在 PCI 结束时在罪犯血管和参考血管中测量的冠状动脉血流储备（CFR）、微血管阻力指数（IMR）和 FFR 的变化，以及 2）充气过程中的心绞痛评分。这项研究于 2018 年开始，目标是纳入 100 名患者。根据 FFR 下降至 30%的比率和 10%的脱落率，我们预计在重复球囊充气后 ST 段抬高的平均变化方面，研究组之间会出现 4mm 的绝对差异。所有研究程序均由天主教圣心大学伦理委员会审查和批准。
替格瑞洛与氯吡格雷相比，可能改善缺血耐受和微血管功能，这些作用可能转化为更好的长期临床结局。
EudraCT 编号 2016-004746-28。NCT02701140。试验状态：本文提供的信息指的是研究方案的最终版本（日期为 2017 年 10 月 31 日，第 3.0 版），并包含所有方案修订。招募工作于 2018 年 9 月 18 日开始，目前正在进行中。预计将于 2019 年底完成入组。
罗马 Gemelli 大学综合医院基金会，心血管和胸腔科学术中心，意大利罗马，Largo Agostino Gemelli 8 号，00168。
