Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke

Chen, Hui‐Sheng; Cui, Yu; Li, Xiaoqiu; Wang, Xinhong; Ma, Yu-Tong; Zhao, Yanxin; Han, Jianda; Deng, Chang-Qing; Hong, Maochun; Bao, Ying; Zhao, Lihong; Yan, Ting-Guang; Zou, Ren-Lin; Wang, Hui; Li, Zhuo; Wan, Li-Shu; Zhang, Li; Wang, Lian-Qiang; Guo, Lingjun; Li, Ming-Nan; Wang, Dongqing; Zhang, Qiang; Chang, Da-Wei; Zhao, Hongli; Sun, Jing; Meng, Chao; Zhang, Zai-Hui; Shen, Li-Ying; Ma, Li; Wang, Gui-Chun; Li, Run-Hui; Zhang, Ling; Bi, Chen; Wang, Liyun; Wang, Duolao; Geng, Shi-Mei; Shi, Jing; Sun, Min; Qiu, Xiaoqing; Jiang, Haitao; Zhang, Yujie; Chen, Jingyang; Wang, Ruiping; Bai, Fengshan; Li, Jing; Gong, Xiaohui; Bai, Ying; Li, Yansong; Feng, Ye-Fang; Ha, Chong; Jiang, Chang-Hao; Zhai, Jin-Hua; Han, Bing; Wang, Ye; Wang, Dong‐Yu; Yang, Kaiyuan; Yu, Huan; Yu, Xiu-Kun; Xiao, Hong-Bo; Nie, Chun; Jiao, Zhen; Li, Jingyu; Meng, Zhao-Min; Chen, Shao-Yuan; Song, Xinshan; Xu, Jun; Li, Li; Wang, Xiaoling; Wang, Xiaojie; Zheng, Wen-Xiang; Zheng, Wenxu; Liu, Yajun; Yu, Miao; Feng, Juan

doi:10.1001/jama.2022.13123

Cited by 79 publications

(105 citation statements)

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“…It works through controlled and transient periods of subcritical ischemia to non-vital arteries ( 16 – 18 ), activating endogenous tissue repair mechanisms to exert neuroprotective effects, cardiovascular protection, and promote neurological recovery ( 4 , 19 , 20 ). Recently, Chen and his colleagues published the results of the Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) trial, the largest randomized clinical trial to date of RIC in patients with AIS ( 21 ). This study indicated that 2 weeks of RIC in patients with acute moderate ischemic stroke within 48 h from symptom onset was associated with an increase in the odds of a favorable outcome (modified Rankin Scale [mRS] 0–1) at 90 days ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Chen and his colleagues published the results of the Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) trial, the largest randomized clinical trial to date of RIC in patients with AIS ( 21 ). This study indicated that 2 weeks of RIC in patients with acute moderate ischemic stroke within 48 h from symptom onset was associated with an increase in the odds of a favorable outcome (modified Rankin Scale [mRS] 0–1) at 90 days ( 21 , 22 ). The result of this trial demonstrated that RIC training at the acute stage of ischemic stroke was feasible and improved long-term functional prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Remote ischemic conditioning (RIC) with exercise (RICE) is safe and feasible for acute ischemic stroke (AIS) patients

et al. 2022

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ObjectiveRehabilitation is essential in reducing stroke disability and should be performed as early as possible. Exercise is an established and effective rehabilitation method; however, its implementation has been limited as its very early use exacerbates cerebral injury and is restricted by patients' unstable conditions and disabilities. Remote ischemic conditioning (RIC) is a passive and accessible therapy in acute phases of stroke and appears to have similar neuroprotective effects as exercise. This study assessed the safety and feasibility of the novel rehabilitation strategy—early RIC followed by exercise (RICE) in acute ischemic stroke (AIS).MethodsWe conducted a single-center, double-blinded, randomized controlled trial with AIS patients within 24 h of stroke onset or symptom exacerbation. All enrolled patients were randomly assigned, at a ratio of 1:1, to either the RICE group or the sham-RICE group (sham RIC with exercise). Each group received either RIC or sham RIC within 24 h after stroke onset or symptom exacerbation, once a day, for 14 days. Both groups started the exercise routine on day 4, twice daily, for 11 total days. The safety endpoints included clinical deterioration, recurrence of stroke, hemorrhagic transformation, complications, and adverse events resulting from RICE during hospitalization. The efficacy endpoints [Modified Rankin Scale (mRS) score, National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index, and walking ability] were evaluated at admission and 90 days after stroke onset.ResultsForty AIS patients were recruited and completed the study. No significant differences in baseline characteristics were found between the two groups, which included risk factors, stroke severity at admission, pre-morbid disability, and other special treatments. No significant differences were found in the safety endpoints between two groups. Excellent recovery (mRS 0–2) at 3 months was obtained in 55% of the patients with RICE as compared 40% in sham group, but it did not reach a significant level.ConclusionsRICE was safe and feasible for AIS patients, and seems to be a promising early stroke rehabilitation. The results of this study suggest a need for a future randomized and controlled multicenter trial with a larger sample size to determine the efficacy of RICE.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Remote ischemic conditioning (RIC) with exercise (RICE) is safe and feasible for acute ischemic stroke (AIS) patients

et al. 2022

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“…In this issue of JAMA , Chen and colleagues report the results of the Remote Ischemic Conditioning For Acute Moderate Ischemic Stroke (RICAMIS) trial, the largest randomized clinical trial to date of RIC in patients with stroke. The authors report that compared with usual care, RIC was beneficial in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score, 6-16; median, 7) who did not receive tPA or mechanical thrombectomy and were treated within 48 hours of stroke (mean, 25 hours).…”

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confidence: 99%

Remote Ischemic Conditioning

Hess

Blauenfeldt

Andersen

2022

JAMA

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Stroke is the second leading cause of death and disability in the world. 1 In 1996, tissue plasminogen activator (tPA) was approved by the US Food and Drug Administration and remains the only approved pharmacologic agent for treatment of ischemic stroke in the US. 2,3 In 2015, mechanical thrombectomy was shown to be beneficial for large vessel occlusion ischemic stroke, although 50% of patients treated with mechanical thrombectomy remain disabled at 3 months. 4 Due to short time windows for thrombolytic therapy administration and the stroke system infrastructure needed for mechanical thrombectomy, these reperfusion therapies are available to only a small proportion of patients who experience stroke. Worldwide, these treatments are used in less than 5% of patients with stroke, and in many low-income nations they are rarely used. 5 To complement these therapies aimed at ending the ischemic insult by reperfusion, neurovascular investigators have long sought to develop neuroprotective agents that could allow brain parenchyma to better tolerate ischemia prior to reperfusion or reduce reperfusion injury after ischemia ends. However, promising results in preclinical animal models have repeatedly ended in translational failure when randomized clinical trials (RCTs) did not meet their primary end points. This led to reluctance by some pharmaceutical companies to invest in developing new medications for stroke treatment and pivoting by the National Institutes of Health to invest in a multicenter preclinical stroke network to more rigorously select interventions to advance into clinical trial. 6 To redefine the neuroprotection model, the Stroke Treatment Academic Industry Roundtable (STAIR) XI introduced the term cerebroprotection to highlight the importance of protecting the neurovascular unit and whole brain, not solely neurons. 7 The STAIR consensus group also highlighted the desirability of interventions with multiple, pleiotropic mechanisms of action, instead of approaches that target a single injury pathway. 7 Remote ischemic conditioning (RIC), which involves brief, reversible episodes of ischemia and reperfusion in one vascular bed to activate ischemia tolerance in remote tissues and organs, represents a new potential approach for cerebroprotection. 8 Remote conditioning induces multiple protective pathways that elicit a protective and resilient phenotype. In 1986, Murry et al 9 reported that the phenomenon of direct ischemic conditioning in the canine heart by repeatedly clamping/declamping the circumflex artery for 5 min-

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“…In August, JAMA published (Chen et al, 2022) an open label randomized trial from China testing remote ischemic limb conditioning (RIC) in 1,893 patients with acute ischemic stroke. Supported by preclinical literature, the investigators aimed to test a new approach that they advocate is a neuroprotective strategy-inflate a cuff to both arms to cause limb ischemia.…”

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confidence: 99%