Batra Hospital & Medical Research Centre, Delhi, New Delhi, India.
Batra Hospital & Medical Research Centre, Delhi, New Delhi, India.
Am Heart J. 2023 Feb;256:128-138. doi: 10.1016/j.ahj.2022.10.082. Epub 2022 Oct 28.
The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease.
The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events.
In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%.
The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).
FREEDOM 试验的结果对糖尿病合并多血管病变患者行经皮冠状动脉介入治疗（PCI）的作用提出了质疑，该试验表明第一代药物洗脱支架（DES）包括死亡率降低在内的优势优于冠状动脉旁路移植术（CABG）。鉴于更安全和更有效的支架以及明显更好的医疗管理，这些可以追溯到 2012 年的结果需要重新评估。TUXEDO-2 是一项旨在比较印度多血管病变糖尿病患者使用两种当代支架的研究。
TUXEDO-2 研究的主要目的是比较在多血管病变的糖尿病患者中，使用超薄 Supraflex Cruz 支架与 Xience 支架联合当代最佳药物治疗（OMT）进行 PCI 的临床结果。次要目的是比较研究的两个治疗组（Supraflex Cruz + Xience；PCI 组）的临床结果与基于 FREEDOM 试验 CABG 组的衍生目标（历史队列）的 CABG 之间的临床结果。次要目的是比较替格瑞洛与普拉格雷加阿司匹林用于缺血和出血事件的复合终点。
在这项前瞻性、开放标签、多中心、2×2 析因、随机、对照研究中，将 1800 例有糖尿病和多血管病变（与 FREEDOM 试验相似的纳入标准）并需要冠状动脉血运重建的患者随机分配至 Supraflex Cruz 或 Xience 支架，并接受替格瑞洛或普拉格雷的抗血小板治疗策略。所有患者将接受指南指导的 OMT 和最佳 PCI，包括可行时进行图像和生理学指导的完全血运重建。患者将随访 5 年，以评估其临床状况和主要临床事件。主要终点是在一年时比较 Supraflex Cruz 与 Xience 的靶病变失败率（一级目标），预期事件发生率为 11%，非劣效性边界为 4.5%。对于 PCI 与 CABG（二级目标），主要终点是主要不良心脏事件（MACE），定义为一年时所有原因死亡、非致死性心肌梗死或卒中和 5 年时每年的复合终点，预期事件发生率为 21.6%。对于替格瑞洛与普拉格雷（三级目标），主要终点是根据出血学术研究联合会（BARC）定义的一年时的死亡、心肌梗死、卒中和大出血复合终点，预期事件发生率为 15%，非劣效性边界为 5%。
TUXEDO-2 研究是一项涉及最先进的 PCI 联合指南指导的 OMT 的当代研究，涉及一组复杂的糖尿病合并多血管病变患者。该试验将回答以下问题：在当前更安全、更有效的支架和现代药物治疗时代，生物可降解聚合物涂层的超薄 Supraflex Cruz 支架是否是多血管病变糖尿病患者 PCI 的一个有吸引力的选择。它还将有助于解决 FREEDOM 试验的结果在当前更安全和更有效的支架和现代药物治疗时代是否会有所不同的问题。此外，还将评估替格瑞洛与普拉格雷加阿司匹林相比的疗效和安全性。（CTRI/2019/11/022088）。
