在一项大型随机临床试验中确定高风险入组标准及其对临床结局的影响：来自TWILIGHT试验的见解
Characterizing high-risk enrollment criteria and impact on clinical outcomes in a large randomized clinical trial: Insights from the TWILIGHT trial.
作者信息
Steg Philippe Gabriel, Nicolas Johny, Baber Usman, Sartori Samantha, Zhang Zhongjie, Feng Yihan, Angiolillo Dominick J, Briguori Carlo, Cohen David J, Collier Timothy, Dangas George, Dudek Dariusz, Escaned Javier, Gibson C Michael, Han Ya-Ling, Huber Kurt, Kastrati Adnan, Kaul Upendra, Marx Steven O, Kornowski Ran, Kunadian Vijay, Vogel Birgit, Oliva Angelo, Mehta Shamir R, Moliterno David, Sardella Gennaro, Krucoff Mitchell, Shlofmitz Richard A, Sharma Samin, Pocock Stuart, Mehran Roxana
机构信息
Université Paris-Cité, INSERM-UMR1148, 22 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, and 23 Institut Universitaire de France, Paris.
Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, NY.
出版信息
Am Heart J. 2025 Aug;286:97-107. doi: 10.1016/j.ahj.2025.01.016. Epub 2025 Jan 30.
BACKGROUND
The TWILIGHT trial showed that, among high-risk patients who underwent percutaneous coronary intervention (PCI) and were event-free at 3 months, ticagrelor monotherapy versus ticagrelor plus aspirin reduced bleeding without increasing ischemic events.
METHODS
This posthoc analysis describes the risk profiles and outcomes of patients enrolled in the TWILIGHT trial. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, and the key secondary outcome was a composite of death, myocardial infarction, or stroke within 1 year after randomization.
RESULTS
The proportion of patients (n = 7,119) fulfilling ≤ 3, 4, 5, or ≥ 6 risk factors was 21.5%, 32.7%, 27.4%, and 18.4%, respectively. Troponin-positive acute coronary syndrome (ACS) was the most prevalent clinical criterion (64.9%), and multivessel disease (MVD) was the most prevalent angiographic criterion (66.5%). The most frequent intersection of criteria was the combination of troponin-positive ACS, atherosclerotic vascular disease, MVD, left main or proximal anterior descending lesion, and stent length > 30 mm. A stepwise increase in ischemic but not in bleeding risk was noted with an increasing number of high-risk criteria. Compared with ticagrelor plus aspirin, ticagrelor monotherapy reduced bleeding regardless of the number of risk factors (≤ 3-RF: 3.5% vs 5.8%, HR 0.59, 95% CI [0.38-0.93]; 4-RF: 3.7% vs 6.4%, HR 0.57, 95% CI [0.37-0.86]; 5-RF: 3.8% vs 8.6%, HR 0.44, 95% CI [0.29-0.66]; ≥ 6-RF: 5.3% vs 7.9%, HR 0.65, 95% CI [0.44-0.96]; p-interaction = .56) without significantly increasing the ischemic risk (≤ 3-RF: 1.6% vs 2.1%, HR 0.75, 95% CI [0.38-1.50]; 4-RF: 3.5% vs 2.2%, HR 1.58, 95% CI [0.91-2.75]; 5-RF: 4.1% vs 5.0%, HR 0.80, 95% CI [0.51-1.24]; ≥ 6-RF: 6.7% vs 6.9%, HR 0.98, 95% CI [0.67-1.43]; p-interaction = .22).
CONCLUSIONS
In the TWILIGHT trial, the high-risk features correlated more strongly with ischemic than with bleeding risk. Nonetheless, the benefits of ticagrelor compared with ticagrelor plus aspirin were consistent, irrespective of the number of high-risk features. These findings are only applicable to patients who are event-free at 3 months after PCI.
CLINICAL TRIAL REGISTRATION
The trial was registered with ClinicalTrials.gov, NCT02270242.
背景
TWILIGHT试验表明，在接受经皮冠状动脉介入治疗（PCI）且3个月无事件的高危患者中，替格瑞洛单药治疗与替格瑞洛联合阿司匹林相比，可减少出血且不增加缺血事件。
方法
这项事后分析描述了TWILIGHT试验中入组患者的风险特征和结局。主要结局为出血学术研究联盟（BARC）2、3或5型出血，关键次要结局为随机分组后1年内死亡、心肌梗死或卒中的复合事件。
结果
符合≤3、4、5或≥6个危险因素的患者比例（n = 7119）分别为21.5%、32.7%、27.4%和18.4%。肌钙蛋白阳性急性冠状动脉综合征（ACS）是最常见的临床标准（64.9%），多支血管病变（MVD）是最常见的血管造影标准（66.5%）。最常见的标准交集是肌钙蛋白阳性ACS、动脉粥样硬化性血管疾病、MVD、左主干或前降支近端病变以及支架长度>30 mm的组合。随着高危标准数量的增加，缺血风险呈逐步上升趋势，但出血风险未增加。与替格瑞洛联合阿司匹林相比，替格瑞洛单药治疗无论危险因素数量多少均可减少出血（≤3个危险因素：3.5%对5.8%，HR 0.59，95%CI[0.38 - 0.93]；4个危险因素：3.7%对6.4%，HR 0.57，95%CI[0.37 - 0.86]；5个危险因素：3.8%对8.6%，HR 0.44，95%CI[0.29 - 0.66]；≥6个危险因素：5.3%对7.9%，HR 0.65，95%CI[0.44 - 0.96]；p交互作用 = 0.56），且不显著增加缺血风险（≤3个危险因素：1.6%对2.1%，HR 0.75，95%CI[0.38 - 1.50]；4个危险因素：3.5%对2.2%，HR
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