Intensive Medical Therapy for High-risk Intracranial or Extracranial Atherosclerosis

Summary

Large-artery stenosis plays an important role in the occurrence of ischemic stroke. The primary purpose of this study is to evaluate the efficacy and safety of intensive antiplatelet therapy versus standard antiplatelet therapy and immediate high-intensity statin therapy (80mg atorvastatin) versus delayed high-intensity statin therapy (40mg atorvastatin) and intensive antiplatelet combined with immediate high-intensity statin therapy (80mg atorvastatin) versus standard antiplatelet combined with delayed high-intensity statin therapy (40mg atorvastatin) in reducing the risk of stroke at 90 days in patients with acute and high-risk symptomatic extracranial or intracranial arterial stenosis.

Timeline

Start

2018-09-17

Primary completion

2023-01-15

Completion

2023-10-30

Publications

• Xia Z, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Wang X, Gao P, Yan H, Wang T, Yang Y, Zhang Y, Wang Y, Wang Y, Pan Y. Efficacy and safety of dual antiplatelet treatment up to 72 hours after mild ischemic stroke or transient ischemic attack in patients with established cardiovascular disease. Neurotherapeutics. 2026 Jul 10;23(4):e00963. doi: 10.1016/j.neurot.2026.e00963. Online ahead of print.
• Li X, Gao Y, Yan H, Wang Y, Pan Y, Guan L, Wang Y. Efficacy and safety of clopidogrel and aspirin initiated within 72 hours after mild ischemic stroke or high-risk TIA by sex: a prespecified subgroup analysis of the INSPIRES trial. Expert Rev Cardiovasc Ther. 2026 Jul 2:1-11. doi: 10.1080/14779072.2026.2696285. Online ahead of print.
• Pan Y, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Jing J, Wang C, Jiang L, Yan H, Wang X, Yang Y, Wang T, Meng X, Lin J, Zhao X, Liu L, Wang Y, Wang Y. Dual Antiplatelet Therapy and Immediate Intensive Statin in Mild Ischemic Stroke: A Randomized Trial. Neurology. 2026 Jul 28;107(2):e218128. doi: 10.1212/WNL.0000000000218128. Epub 2026 Jun 25.
• Cheng M, Li H, Gao Y, Yan H, Liu X, Yang Y, Chen W, Wang Y, Pan Y, Wang Y. White matter hyperintensities and 90-day outcomes in patients with mild ischaemic stroke or high-risk TIA. Stroke Vasc Neurol. 2026 Apr 16:svn-2025-004529. doi: 10.1136/svn-2025-004529. Online ahead of print.
• Liu C, Li Y, Liu Z, Gao Y, Zhang Q, Wabnitz AM, Pan Y, Yan H, Chen W, Johnston SC, Wang D, Amarenco P, Bath PM, Wang Y, Wang Y, Guan L. The effect of dual antiplatelet therapy in different patterns of watershed infarction: Subgroup analysis of the INSPIRES trial. Cell Rep Med. 2026 Feb 17;7(2):102596. doi: 10.1016/j.xcrm.2026.102596. Epub 2026 Feb 5.
• Chen Y, Jiang L, Gao Y, Chen W, Yan H, Wang T, Yang Y, Yao D, Liu D, Pan Y, Wang Y. CYP2C19 Genotype and Efficacy of Clopidogrel Initiated Between 24 to 72 Hours for Ischemic Stroke. Stroke. 2025 Nov;56(11):3108-3117. doi: 10.1161/STROKEAHA.125.052167. Epub 2025 Sep 18.
• Xia Z, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Wang X, Yan H, Wang T, Yang Y, Zhang Y, Wang M, Jing J, Wang C, Wang Y, Wang Y, Pan Y. Dual Antiplatelet Therapy in Patients With Metabolic Syndrome After Mild Ischemic Stroke or Transient Ischemic Attack. J Am Heart Assoc. 2025 Aug 5;14(15):e041449. doi: 10.1161/JAHA.125.041449. Epub 2025 Jul 17.
• Liu D, Yan H, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Wang X, Wang M, Wang T, Yang Y, Jing J, Wang C, Wang Y, Pan Y, Wang Y. Effect of history of hypertension on efficacy of clopidogrel-aspirin in ischemic stroke. Int J Stroke. 2025 Oct;20(8):1021-1030. doi: 10.1177/17474930251338618. Epub 2025 Apr 19.
• Li H, Cheng M, Gao Y, Yan H, Wang Y, Johnston SC, Bath PM, Amarenco P, Yang Y, Chen W, Wang Y, Pan Y, Wang Y. Does the Burden of CSVD Modify the Efficacy of Dual Antiplatelet Therapy?: A Post Hoc Analysis of the INSPIRES Trial. Stroke. 2025 Jun;56(6):1376-1387. doi: 10.1161/STROKEAHA.124.049826. Epub 2025 Apr 7.
• Zhou Q, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Wang X, Yan H, Wang T, Yang Y, Zhang Y, Yang Q, Wang M, Jing J, Wang C, Wang Y, Wang Y, Pan Y. Efficacy and Safety of Dual Antiplatelet Treatment up to 72 Hours in Acute Ischemic Stroke Stratified by Glycemic Status. Ann Neurol. 2025 Jul;98(1):174-182. doi: 10.1002/ana.27207. Epub 2025 Feb 11.
• Zhang Y, Wang X, Gao Y, Chen W, Johnston SC, Amarenco P, Bath PM, Yan H, Wang T, Yang Y, Zhou Q, Wang M, Jing J, Wang C, Wang Y, Wang Y, Pan Y. Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis. Stroke. 2025 Jan;56(1):46-55. doi: 10.1161/STROKEAHA.124.049246. Epub 2024 Dec 20.
• Guan L, Han S, Johnston SC, Bath PM, Amarenco P, Yang Y, Wang T, Jing J, Wang C, Gao Y, Chen W, Yan H, Wang X, Wang Y, Wang Y, Pan Y. Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack. Neurology. 2024 Oct 8;103(7):e209845. doi: 10.1212/WNL.0000000000209845. Epub 2024 Sep 13.
• Liu Y, Zhao J, Gao Y, Chen W, Johnston SC, Bath PM, Amarenco P, Yan H, Wang X, Yang Y, Wang T, Wang Y, Pan Y, Wang Y. Clopidogrel and Aspirin Initiated Between 24 to 72 Hours for Mild Ischemic Stroke: A Subgroup Analysis of the INSPIRES Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2431938. doi: 10.1001/jamanetworkopen.2024.31938.
• Gao Y, Jiang L, Pan Y, Chen W, Jing J, Wang C, Johnston SC, Amarenco P, Bath PM, Yang Y, Wang T, Han S, Meng X, Lin J, Zhao X, Liu L, Zhao J, Li Y, Zang Y, Zhang S, Yang H, Yang J, Wang Y, Li D, Wang Y, Liu D, Kang G, Wang Y, Wang Y; INSPIRES Investigators. Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial. JAMA Neurol. 2024 Jul 1;81(7):741-751. doi: 10.1001/jamaneurol.2024.1433.
• Gao Y, Chen W, Pan Y, Jing J, Wang C, Johnston SC, Amarenco P, Bath PM, Jiang L, Yang Y, Wang T, Han S, Meng X, Lin J, Zhao X, Liu L, Zhao J, Li Y, Zang Y, Zhang S, Yang H, Yang J, Wang Y, Li D, Wang Y, Liu D, Kang G, Wang Y, Wang Y; INSPIRES Investigators. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. N Engl J Med. 2023 Dec 28;389(26):2413-2424. doi: 10.1056/NEJMoa2309137.
• Gao Y, Pan Y, Han S, Chen W, Jing J, Wang C, Yang Y, Wang T, Meng X, Zhao X, Liu L, Li H, Johnston SC, Amarenco P, Bath PM, Wang Y, Wang Y; INSPIRES Investigators. Rationale and design of a randomised double-blind 2x2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis (INSPIRES). Stroke Vasc Neurol. 2023 Jun;8(3):249-258. doi: 10.1136/svn-2022-002084. Epub 2023 Jan 27.

Drugs

Indications