Video Editor's Note: Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke

I’m Dr Jeffrey Saver, JAMA Associate Editor and SA Vice Chair of Neurology at UCLA Health. Welcome to this video editor’s note for the RICAMIS trial, published in the August 16, 2022, issue of JAMA. I’d like to discuss some of the aspects of this study that I found particularly interesting.

Currently, the only proven therapies for acute ischemic stroke are reperfusion therapies, intravenous thrombolysis and endovascular thrombectomy. These are most often started within 4.5 to 6 hours after onset. But clinical data are accumulating on remote ischemic conditioning, or RIC, which is a different type of therapy. It doesn’t restore blood flow, but rather is thought to induce brain resistance to hypoxia and induce neuroplasticity, through humoral factors generated by ischemia in another vascular bed. Also, RIC potentially may be started substantially later after onset.

The RICAMIS trial investigated RIC as a treatment for patients with moderate ischemic stroke within 48 hours of onset. The trial randomized 1893 individuals at 55 hospitals in China. Patients allocated to remote ischemic conditioning added to standard care were treated twice a day, for 10-14 days, with 5 cycles of 5-minute inflation of bilateral arm cuffs to above systolic and 5-minute deflation. Control patients received standard care only. Nondisabled outcome at 90 days, the primary endpoint, was achieved more often with RIC, 67.4% vs 62.0%, with a p value of 0.02. Adverse events related to cuff inflation were uncommon, with arm redness, arm petechiae, or dizziness occurring in 6 patients. Limitations included the trial’s open-label design and a relatively high dropout rate of 9%.

The size of the treatment effect observed in the trial is moderate, but clinically relevant. Out of every 100 patients treated, 5.5 more achieved a long-term outcome of freedom from disability. This is less than the effect of IV thrombolysis started within 3 hours, which yields freedom from disability in 13 of every 100 treated patients. Since freedom from disability matters greatly to patients, the minimal clinically important difference for this outcome is 1-2 per 100, which the observed treatment effect exceeded.

Should this study change the way clinicians practice? Not yet. This is the first positive trial of remote ischemic conditioning for ischemic stroke. Two prior trials had neutral results, though they tested a different strategy of only using treatment within the first hours after onset. Given the discrepant results of the RICAMIS trial compared with those precedents and some trial limitations, further trials are clearly needed before remote ischemic conditioning can be recommended for use in practice. But the RICAMIS trial did have some promising results that will undoubtedly stimulate further trials and potentially lead to an entirely new type of treatment for ischemic stroke.