Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
Pierre Amarenco, Hans Denison, Scott Evans, Anders Himmelmänn, Stefan James, Mikael Knutsson, Per Ladenvall, Carlos A. Molina, Yongjun Wang, S. Claiborne Johnston, Kenneth Butcher, Shuya Li, Huaguang Zheng, David Školoudík, Ka Sing Wong, К С Мешкова, Nijasri C. Suwanwela, Sebastián F. Ameriso, Leonardo Gonzalez, Pablo Ioli, Lorena Jure, Guillermo Povedano, Guadalupe Bruera, Gustavo Herrera, Juan Jose Martin Artesi, Virginia Pujol Lereis, Conrado J. Estol, Maia Gómez Schneider, Santiago Pigretti, Fernando Lipovestky, María Cristina Zurrú, Stephen C. Davis, Andrew Wong, Tissa Wijeratne, Arman Sabet, Andrew Lee, Vincent Thijs, Robin Lemmens, Laetitia Yperzeele, Geert Vanhooren, Peter Vanacker, Iris Vansteenkiste, Vicky Maqueda, André Peeters, Van Daele Marie-Christine Hasenbroekx, Wendy Hasenbroekx, Adinda De Pauw, Regilio Oedit, Wouter De Vooght, Philippe Desfontaines, Yves Vandermeeren, Adinda De Pauw, Marianna Deway Andrade Dracoulakis, Rodrigo Bazán, Octávio Marques Pontes‐Neto, Daniel Bezerra, Luiz Carlos Porcello Marrone, Pedro André Kowacs, Carla Heloísa Cabral Moro, Paulo Cesar Otero Macelino, Marco Túlio Araújo Pedatella, Еkaterina Titianova, Ivan Staikov, Dimitar Maslarov, Plamen Petkov, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Dimcho Hristov, Rumeliya Mitkova Ivanova, Margarita Velichkova Mihailova, Ashfaq Shuaib, Andrew M. Demchuk, Michel Beaudry, Anthony R Winder, Sumiti Nayar, Xingquan Zhao, Guoqiang Wen, Xueshuang Dong, Guozhong Li, Zhaohui Zhang, Dawei Chen, Dong Wang, Xiaohong Li, Yun‐Cheng Wu, Xu Zhang, Baorong Zhang, Wenke Hong, Xiaogang Li, Lijuan Wang, Li Liu, Xiaolin Xu, Peifu Wang, Weihong Zheng, Jinsheng Zeng, Yukai Wang, Yan Jia, Yongqiu Li, Bo Hu, Wei Shen
Abstract
Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P =0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P =0.23, P interaction =0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively ( P =NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P =0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03354429.