Remote Ischemic Perconditioning in Stroke Shows No Effect on Brain Infarction Growth

Pierre Amarenco, MD

Results from the Remote Ischemic Conditioning in Acute Brain Infarction (RESCUE-BRAIN) study (NCT02189928) demonstrated no significant change in brain infarction volume growth at 24 hours after symptom onset following treatment with remote ischemic perconditioning, during or after infusion therapies, for patients with acute ischemic stroke.

There was a 0.30 cm3 (Interquartile range [IQR], 0.11—0.48 cm3) and 0.37 cm3 median increase in brain infarction growth in the intervention and control groups, respectively (mean between-group difference on loge-transformed change, –0.07; 95% CI, –0.33 to 0.18; P = .57).

“We found that treatment with remote ischemic perconditioning in patients with acute ischemic stroke (as an add-on therapy to reperfusion treatment) had no beneficial effect. We note that, although efforts have been made to improve the quality of preclinical studies (such as the randomization, blinded endpoints, and rodents with comorbidities), the results of such studies do not necessarily indicate what will happen in randomized clinical trials,” senior researcher Pierre Amarenco, MD, chairman, department of Neurology and Stroke Center, Bichat Hospital, and colleagues concluded.

READ MORE: Unfavorable Outcomes Associated With Prolonged Ventilation in Stroke

RESCUE-BRAIN was a prospective, multicenter, proof-of-concept, open-label trial that randomized 188 patients with acute ischemic stroke 1:1 to receive treatment with remote ischemic perconditioning in addition to standard care or standard care alone. Those who received remote ischemic preconditioning (n = 94), otherwise known as the intervention group, underwent 5 cycles of 5-minute inflations and 5-minute deflations to the thigh to 110 mm Hg above systolic blood pressure.

Performed from January 12, 2015 to May 2, 2018, researchers examined the change in brain infarction volume growth between baseline and 24 hours, measured by a diffusion-weighted sequence of MRI scans of the brain. Secondary outcomes included change in brain infarction volume from baseline to 24 hours after first MRI scan, change in National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after symptom onset, and activities of daily living scores at 90 days measured on the Barthel Index for Activities of Daily Living scale.

Patients were eligible for the study if they were age 18 years or older, had a score between 5 and 25 on the NIHSS (score range, 0-42, with 0 indicating no stroke symptoms and 42 indicating severe stroke), had a carotid-territory brain infarction identified through diffusion-weighted MRI scan, and were able to receive treatment with remote ischemic perconditioning within 6 hours of stroke onset.

The mean (SD) age among the 188 patients observed was 67.2 (15.7) years, and the median brain infarction volume was 11.4 cm3 (IQR, 3.6—35.8 cm3). In total, 98 (52.1%) patients were male. Additionally, the median NIHSS score was 10 (IQR, 6–16), with 129 of 188 patients (68.6%) having documented vessel occlusion identified through baseline MRI scan upon hospital admission.

Procedure completion of 4 cycles at a median of 222 minutes (IQR, 176—275 minutes) occurred in 88 of 93 patients (94.6%) in the intervention group. Of the 188 patients included in the entire cohort, 164 (87.2%) received intravenous thrombolysis and 64 (34.0%) underwent mechanical thrombectomy.

In addition to the similarities of infarction growth, investigators noted no significant differences between the intervention and control group on 90-day mortality rates (14 of 90 patients; Kaplan-Meier estimate, 15.8% versus 10 of 91 patients; Kaplan-Meier estimate, 10.4%, respectively; P = .45). Similar observations were found with symptomatic intracranial hemorrhage (4 of 88 patients [4.5%] in both groups; P = .97).

Excellent outcomes on the modified Rankin Scale (mRS), or scores between 0 and 1, were observed in 46 of 90 patients (51.1%) in the intervention group compared to 37 of 91 (40.7%) patients in the control group (P = .12).

REFERENCE

Pico F, Lapergue B, Ferrigno M, et al. Effect of in-hospital remote ischemic perconditioning on brain infarction growth and clinical outcomes in patients with acute ischemic stroke: the RESCUE-BRAIN randomized clinical trial. JAMA Neurol. Published online March 30, 2020. doi: 10.1001/jamaneurol.2020.0326