Remote ischemic conditioning for acute stroke

In a randomized, sham-controlled study published in the Journal of the American Medical Association (JAMA), researchers investigated the effect of remote ischemic conditioning (RIC) on functional outcomes in patients with acute stroke in a combined prehospital and in-hospital setting.

They found that at 90 days, RIC treatment did not significantly improve functional outcomes in patients with acute stroke compared to the control group.

Study: Remote Ischemic Conditioning for Acute Stroke. Image Credit: SewCreamStudio/Shutterstock.com

Background

RIC with transient cycles of limb ischemia and reperfusion is a simple, noninvasive intervention to minimize the risk of ischemic injury to the affected organs. In preclinical studies on intracerebral hemorrhage models, RIC enhances collateral blood flow in the ischemic area and reduces poststroke inflammation.

In clinical trials, RIC was found to be safe, feasible, and effective after 48 hours of stroke. RIC is also shown to be associated with increased hematoma resorption.

However, evidence remains inconclusive on the effectiveness of RIC as a treatment option for acute stroke. Therefore, the present clinical trial aimed to determine whether RIC started in the prehospital setting and repeated in the hospital could improve functional outcomes in patients diagnosed with acute ischemic or hemorrhagic stroke.

About the study

The “remote ischemic conditioning in patients with acute stroke trial” (RESIST) was a randomized, double-blinded, sham-controlled trial conducted at four different centers in Denmark between March 2018 and November 2022, and a follow-up was conducted in February 2023.

The study included 1,500 adult patients who presented to the hospital within four hours of stroke symptoms, as indicated by a prehospital stroke score (PreSS) of one or greater.

The exclusion criteria were a history of intracranial aneurysm, cerebral neoplasm, arteriovenous malformation, brain abscess, progressive neurodegenerative disease, severe peripheral arterial disease in the upper extremities, or the presence of an arteriovenous shunt in the arm selected for RIC.

The “target population” was patients receiving an in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage.

The patients were randomized 1:1 to receive either RIC (n= 749) or sham (n= 751) on one upper extremity using an inflatable cuff. The procedure involved five cycles: cuff inflation (five minutes) followed by deflation (five minutes).

The cuff pressure in the RIC was 200 mmHg, while that in the sham was 20 mmHg. The treatment was initiated in the ambulance and performed again in the hospital at least once. Patients with a target diagnosis were treated twice daily for seven days.

The improvement in functional outcome at 90 days was the primary efficacy endpoint in the target population, measured as a favorable shift in the modified Rankin scale (mRS) score, where 0 implies no symptoms and a score of 6 implies death.

The secondary endpoints were a change in PreSS at 24 hours, severe adverse cardiac or cerebral events at 90 days, recurrent ischemic events, early neurological improvement, length of hospital stay, and all-cause mortality at 90 days.

The statistical analysis involved using Kaplan-Meier curves, Aalen-Johansen curves, and the estimation of odds ratio, relative risks, and difference in means.

Results and discussion

Out of the 1,500 included patients, 1,433 could complete the trial. The mean age of the patients was 71 years, and 41% of them were females. The target population consisted of 902 patients, with 436 in the RIC group and 466 in the sham group.

About 82% of the target population had acute ischemic stroke, while 18% had intracerebral hemorrhage. The two groups were similar regarding the baseline demographic, reperfusion rates, and clinical characteristics. About 90% of patients adhered to the treatment in the target population.

At 90 days, the median mRS score was estimated to be 2 in the RIC group, while that of the sham group was 1 (odds ratio = 0.95). Thus, as per the study, the RIC treatment did not significantly improve functional outcomes in the target population.

The secondary efficacy outcomes, mortality, and serious adverse events did not significantly differ among the two groups.

In a per-protocol analysis conducted on adherent patients, the results obtained were similar to the primary research in the target population. While the study has several limitations, the findings do not demonstrate significant benefits from RIC when applied in patients with acute stroke.

Conclusion

As per the study findings, RIC initiated in prehospital settings and continued in the hospital did not improve functional outcomes significantly at 90 days in patients with a confirmed diagnosis of acute ischemic stroke or intracerebral hemorrhage.

These results suggest that RIC may not be an effective standalone treatment for acute stroke. However, its role as an adjunctive therapy needs to be evaluated through further research.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.