Remote Ischemic Conditioning in Acute Stroke: A Disheartening Verdict from Rigorous Trials

In the relentless pursuit of groundbreaking stroke treatments, the medical community has explored various avenues, including remote ischemic conditioning (RIC). Initial excitement surrounded RIC with promising preclinical and clinical data suggesting its potential efficacy. However, a recent comprehensive clinical trial has challenged these optimistic expectations, dealing a significant blow to the hopes of revolutionizing acute stroke care. 

RIC is a simple and noninvasive procedure involving transient cycles of limb ischemia and reperfusion on the upper extremity leading to distant organ protection in preclinical and clinical studies. The early effects exhibit enhanced collateral blood flow in the ischemic area and reduced post-stroke inflammation. Previous studies showed significantly improved functional outcomes in acute ischemic stroke. However, due to some uncertainty Danish researchers conducted a randomized, sham-controlled, multicenter clinical trial to determine whether combined prehospital and in-hospital RIC treatment improves functional outcomes in patients with acute ischemic and hemorrhagic stroke. 

The trial, conducted from March 2018 to November 2022, enrolled 1,500 patients with prehospital stroke symptoms lasting less than four hours. The study aimed to assess the impact of RIC initiated in the prehospital setting and continued in the hospital. Patients were randomly divided into two groups: one receiving RIC treatment and the other a sham treatment. The primary measure of success was an improvement in functional outcomes, evaluated on the modified Rankin Scale (mRS), 90 days post-stroke. 

Findings: 

• The results, however, were far from what researchers and medical professionals had hoped for. Among the 902 stroke-diagnosed patients, RIC failed to significantly enhance functional outcomes at the critical 90-day mark.
• The mRS scores revealed no substantial difference between the group that received RIC (mRS score at 90 days was 2) and the one subjected to the sham treatment (mRS score at 90 days was 1).
• Moreover, both groups experienced a similar number of serious adverse events (RIC vs Sham 169 vs 175), indicating that RIC did not provide a safer alternative. 
•  Interestingly, upper extremity pain during treatment and skin petechia were notably higher in the RIC group, highlighting the discomfort associated with this intervention. 

Thus, this study deals a significant blow to the hopes pinned on RIC as a groundbreaking stroke treatment. Despite its promise in prior studies, the meticulous scrutiny of a randomized clinical trial has shown that RIC, when initiated in the prehospital phase and sustained in the hospital, does not yield meaningful improvements in stroke patients' functional outcomes. 

Further reading: Blauenfeldt RA, Hjort N, Valentin JB, et al. Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial. JAMA. 2023;330(13):1236–1246. doi:10.1001/jama.2023.16893