Remote Ischemic Conditioning Improves Likelihood of Excellent Outcomes in Post Stroke

David C. Hess, MD

Findings from the RICAMIS trial (NCT03740971) of adults with acute ischemic stroke demonstrated that treatment with remote ischemic conditioning (RIC) significantly improved the odds patients achieved excellent functional outcomes at 90 days.¹

The investigators included Hui-Sheng Chen, MD, of the General Hospital of Northern Theatre Command, in Shenyang, China. Following treatment, the proportion of patients with a modified Rankin Scale (mRS) score of 0 to 1, considered excellent functional outcome, was 67.4% (582 of 863) in the RIC group and 62.0% (566 of 913) in the control group, yielding an unadjusted odds ratio (OR) of 1.27 (95% CI, 1.05-1.54; P = .02) and risk ratio of 1.17 (95% CI, 1.03-1.32; P = .02). RIC was also shown to be safe, as indicated by a similar proportion of patients who experienced adverse events (6.8%) relative to the control group (5.6%).

Although promising, these findings need replication in another trial before concluding efficacy for this intervention, Chen et al noted.¹ In a related editorial, David C. Hess, MD, et al wrote, "If the results of the RICAMIS study reported by Chen et al are confirmed in other RCTs and in different populations, RIC may be the first cerebroprotective therapy to prove translatable to humans. In that case, RIC could represent a feasible, safe treatment that would not require a large infrastructure and the intervention could be applied in a variety of settings without specialized personnel."²

In this open-label, blinded-end point clinical trial, patients with acute moderate ischemic stroke were randomly assigned within 48 hours after symptom onset to receive treatment with RIC for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). RIC was conducted using a pneumatic electronic device and consisted of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg. After the blood pressure inflation target was set in the device by a trained nurse, the electronic tourniquet automatically delivered the cycles.¹

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Of the 1893 patients originally enrolled, 96.1% (1707) completed the RIC procedure according to protocol. In the RIC group, 808 of 863 patients (93.6%) underwent the complete procedure of 8 to 16 days of RIC treatment at a mean of 24.8 hours from symptom onset to the first cuff inflation. Of the remaining 55 patients, 46 received 1 days of RIC treatment, 1 received 5 days, 1 received 6 days, and 7 received 7 days.

On secondary outcomes, 79.6% of patients in the RIC group had mRS score of 0 to 2 within 90 days, compared with 75.5% in the control grouo, yielding an unadjusted OR of 1.20 (95% CI, 1.01-1.43; P = .04) and an adjusted OR of 1.22 (95% CI, 1.03-1.45; P = .02). All other secondary outcomes, which included early neurologic deterioration within 7 days, stroke-associated pneumonia within 12 days, change in National Institute of Health Stroke Scale (NIHSS) score at day 12, stroke or other vascular events within 90 days, and death within 90 days, were not significant.

In a prespecified subgroup analysis, there was no significant treatment heterogeneity in the odds of having a primary outcome between the RIC and control group by age, sex, NIHSS score at randomization, time from the onset of symptom to RIC treatment, degree of responsible vessel stenosis, location of stenosis, and presumed stroke cause. With respect to RIC-related adverse events (AEs) in the RIC group, 6 patients experienced AEs, including 3 with redness or swelling in the arms, 2 with skin petechiae on the arms, and 1 with dizziness.

Hess et al added that, "RIC has advantages over thrombolytics. It appears to be safe and also may be effective in intracerebral hemorrhage. In a mouse model, RIC reduced intracerebral hemorrhage hematoma volume and improved functional outcome with the mechanism involving anti-inflammatory macrophages expressing CD36. Therefore, this approach could potentially be attractive as an out-of-hospital intervention or in settings where early brain imaging cannot be performed."²

REFERENCES
1. Chen H, Cui Y, Li X, et al. Effect of remote ischemic conditioning vs usual care on neurologic function in patients with acute moderate ischemic stroke: the RICAMIS randomized clinical trial. JAMA Neurol. 2022;328(7):627-636. doi:10.1001/jama.2022.13123
2. Hess DC, Blauenfeldt RA, Anderson G. Remote ischemic conditioning: feasible and potentially beneficial for ischemic stroke. JAMA Neurol. 2022;328(7):622-624. doi:10.1001/jama.2022.13365