Remote Ischemic Conditioning Combined With Endovascular Stenting for Symptomatic Intracranial Atherosclerotic Stenosis

Safety and Efficacy of Remote Ischemic Conditioning Combined With Endovascular Stenting in Patients With Symptomatic Intracranial Atherosclerotic Stenosis

The purpose of this registry is to evaluate the safety and efficacy of RIC for patients with symptomatic intracranial atherosclerotic stenosis (sICAS) undergoing endovascular therapy.

Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke, and its incidence varies widely among different ethnic groups. ICAS may represent approximately 10% of ischemic stroke in Caucasians and even be responsible for up to 50% in Chinese population. Recurrent stroke risks are as high as 23% 1 year after transient ischemic stroke (TIA) or stroke in patients with a stenosis of 70% or more. The Chinese IntraCranial AtheroSclerosis (CICAS) study indicated the prevalence of ICAS was 46.6%; Patients with ICAS had more severe stroke at admission and stayed longer in hospitals compared with those without intracranial stenosis. After 12 months, recurrent stroke occurred in 3.27% of patients with no stenosis, in 3.82% for those with 50% to 69% stenosis, in 5.16% for those with 70% to 99% stenosis, and in 7.27% for those with total occlusion.

Current guidelines recommend best medical treatment (BMM) for patients with sICAS, which contains antithrombotic therapy, management of vascular risk factor (diabetes, lipids, and especially hypertension) and patient behaviors modification (diet, exercise and smoking cessation). But, even with the intervention of BMM, the recurrence of ischemic stroke or transient ischemic attacks (TIAs) in patients with sICAS still cannot be reduced. Endovascular therapy with intracranial angioplasty and/or stenting holds great promise as a treatment for sICAS. A recent trial found that, compared with bare-metal stent, drug-eluting stent reduced the risks of In-stent restenosis and ischemic stroke recurrence in patients with sICAS. However, endovascular therapy for patients with sICAS is known to be associated with potentially serious complications such as cerebral hyper-perfusion syndrome, intracranial hemorrhage, embolism and In-stent restenosis, etc. Those are the main reasons that affect the effect of endovascular therapy, thus limiting its application and popularization to a great degree.

Remote Ischemic Conditioning (RIC) is one of the most potent neuroprotective approaches that can minimize neuronal damage by protecting against ischemia-reperfusion injury and promote neuronal recovery by stimulating endogenous protective mechanism through transiently occluding the blood supply to non-significant organs or tissues such as limbs. The investigators see a promising future for RIC in facilitating further clinical translation and application due to its unique features of safety, simplicity and non-invasiveness. In recent years, the safety and efficacy of RIC on stroke intervention has been confirmed by a series of basic and clinical researches, among which RIC in combination with adjuvant drug therapy for sICAS-induced ischemic stroke patient improve cerebral blood flow and reduce stroke recurrence. Since its safety and efficacy has been verified, RIC can also be used to reduce the risks of In-stent restenosis for patients with carotid stent implantation and has extensive application prospects for patients with severe acute ischemic stroke treated with endovascular thrombectomy.

There is not enough evidence as to provide any specific recommendation regarding the use of RIC in sICAS patients, But we speculate that RIC has a certain effect on preventing perioperative complications for patients with sICAS undergoing endovascular therapy. Therefore, we intend to conduct this prospective cohort study to shed light on the utility of this promising therapy.

This study prospectively collects data of patients with sICAS who receive endovascular therapy in the Comprehensive Neurovascular Ward of Tianjin Huanhu Hospital. Depending on their preference, patients enrolled in this registry will be divided into 2 groups, receiving either endovascular therapy alone or endovascular therapy plus RIC respectively.

Inclusion Criteria:

1. Patient admitted from Jan. 1st 2023 to Jan. 1st 2025;
2. Age ≥ 18;
3. Intracranial atherosclerosis stenosis measured as ≥70% by digital subtraction angiography or by other noninvasive methods, such as transcranial doppler, computed tomography angiography, or magnetic resonance angiography;
4. A history of stroke/transient ischemic attack attributed to ICAS;
5. Verbal and written informed consent is provided at the time of admission by patients or their legally authorized representatives.

Exclusion Criteria:

1. Stenosis of other causes;
2. Prior ipsilateral stroke with residual deficits;
3. Uncontrolled hypertension (defined as systolic blood pressure ≥200 mm Hg despite medications at enrollment);
4. Peripheral vascular disease (especially subclavian arterial and upper limb artery stenosis or occlusion).