Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study

Shimeng Liu; Zongen Gao; Ran Meng; Haiqing Song; Tianping Tang; Ya Zhao; Rong Chen; Yanzhen Sheng; Qianqian Fan; Fang Jiang; Qian Zhang; Jianping Ding; Xiaoqin Huang; Qingfeng Ma; Kai Dong; Sufang Xue; Zhipeng Yu; Jiangang Duan; Changbiao Chu; Xiaohui Chen; Xingquan Huang; Sijie Li; Bruce Ovbiagele; Wenle Zhao; Xunming Ji; Wuwei Feng

doi:10.3389/fneur.2021.748916

Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study

Front Neurol. 2021 Dec 16:12:748916. doi: 10.3389/fneur.2021.748916. eCollection 2021.

Authors

Shimeng Liu^{1

2}, Zongen Gao³, Ran Meng¹, Haiqing Song¹, Tianping Tang³, Ya Zhao⁴, Rong Chen⁵, Yanzhen Sheng⁴, Qianqian Fan⁵, Fang Jiang¹, Qian Zhang¹, Jianping Ding¹, Xiaoqin Huang¹, Qingfeng Ma¹, Kai Dong¹, Sufang Xue¹, Zhipeng Yu¹, Jiangang Duan¹, Changbiao Chu¹, Xiaohui Chen³, Xingquan Huang⁴, Sijie Li¹, Bruce Ovbiagele⁶, Wenle Zhao⁷, Xunming Ji^{1

8

9

10

11

12

13

14}, Wuwei Feng^{2

15}

Affiliations

¹ Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
² Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Neurology, Shengli Oilfield Center Hospital, Dongying, China.
⁴ Department of Neurology, Taoyuan People's Hospital, Changde, China.
⁵ Department of Neurology, First Affiliated Hospital of Hainan Medical University, Haikou, China.
⁶ Departmeng of Neurology, University of California, San Francisco, San Francisco, CA, United States.
⁷ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States.
⁸ Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China.
⁹ Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
¹⁰ Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China.
¹¹ China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
¹² Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
¹³ Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
¹⁴ Beijing University of Aeronautics & Astronautics-China Capital Medical University (BUAA-CCMU) Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing, China.
¹⁵ Department of Neurology, Duke University School of Medicine, Durham, NC, United States.

Abstract

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months. Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days. Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions. Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

Keywords: acute minor ischemic stroke; remote ischemic conditioning; secondary prevention; stroke; transient ischemic attack.