Remote Ischemic Conditioning for Acute Stroke : The RESIST Randomized Clinical Trial
(2023) In JAMA 330(13). p.1236-1246- Abstract
Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff... (More)
Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P =.67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P =.68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.
(Less)
- author
- organization
- publishing date
- 2023-10-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JAMA
- volume
- 330
- issue
- 13
- pages
- 11 pages
- publisher
- American Medical Association
- external identifiers
-
- pmid:37787796
- scopus:85172987947
- ISSN
- 0098-7484
- DOI
- 10.1001/jama.2023.16893
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2023 S. Karger AG, Basel.
- id
- 8b28b426-3cc8-493c-86f5-b604b11b7161
- date added to LUP
- 2023-12-04 16:42:49
- date last changed
- 2024-04-17 13:40:10
@article{8b28b426-3cc8-493c-86f5-b604b11b7161,
abstract = {{<p>Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P =.67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P =.68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.</p>}},
author = {{Blauenfeldt, Rolf Ankerlund and Hjort, Niels and Valentin, Jan Brink and Homburg, Anne Mette and Modrau, Boris and Sandal, Birgitte Forsom and Gude, Martin Faurholdt and Hougaard, Kristina Dupont and Damgaard, Dorte and Poulsen, Marika and Diedrichsen, Tove and Schmitz, Marie Louise and Von Weitzel-Mudersbach, Paul and Christensen, Alex Alban and Figlewski, Krystian and Grove, Erik Lerkevang and Hreiðarsdóttir, Margrét Katrín and Lassesen, Henning Morthorst and Wittrock, Daniel and Mikkelsen, Søren and Væggemose, Ulla and Juelsgaard, Palle and Kirkegaard, Hans and Rostgaard-Knudsen, Martin and Degn, Niels and Vestergaard, Sigrid Breinholt and Damsbo, Andreas Gammelgaard and Iversen, Ane Bull and Mortensen, Janne Kærgård and Petersson, Jesper and Christensen, Thomas and Behrndtz, Anne Brink and Bøtker, Hans Erik and Gaist, David and Fisher, Marc and Hess, David Charles and Johnsen, Søren Paaske and Simonsen, Claus Ziegler and Andersen, Grethe}},
issn = {{0098-7484}},
language = {{eng}},
month = {{10}},
number = {{13}},
pages = {{1236--1246}},
publisher = {{American Medical Association}},
series = {{JAMA}},
title = {{Remote Ischemic Conditioning for Acute Stroke : The RESIST Randomized Clinical Trial}},
url = {{http://dx.doi.org/10.1001/jama.2023.16893}},
doi = {{10.1001/jama.2023.16893}},
volume = {{330}},
year = {{2023}},
}