Safety and Efficacy of Remote Ischemic Preconditioning in Patients with Severe Carotid Artery Stenosis Prior to Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial
Background—Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear that whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis.
Methods—Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham and no intervention (control) groups. All subjects received standard medical therapy. Subjects in the RIPC and sham groups underwent RIPC and sham RIPC twice daily respectively for 2 weeks prior to CAS. Plasma NSE and S-100B were used to evaluate safety, hypersensitive C-reactive protein (hs-CRP) and new ischemic DWI lesions were used to determine treatment efficacy. The primary outcomes were the presence of ≥ 1 newly ischemic brain lesions on DWI within 48 hours after stenting and clinical events within 6 months after stenting.
Results—We randomized 189 subjects in this study (63 subjects in each group). Both RIPC and sham RIPC procedures were well tolerated and completed with high compliance (98.41% and 95.24% respectively). Neither plasma NSE levels nor S-100B levels changed significantly before and after treatment. No severe adverse event was attributed to RIPC and sham RIPC procedures. The incidence of new DWI lesions in the RIPC group (15.87%) was significantly lower than the sham group (36.51%; RR 0.44; 96% CI 0.20 to 0.91, p<0.01) and the control group (41.27%; RR 0.39, 96% CI 0.21 to 0.82; p<0.01). The volumes of lesions were smaller in the RIPC group compared to the control and sham groups (p<0.01 each). Ischemic events occurred after CAS were 1 TIA in RIPC group, 2 strokes in control group and two strokes and one TIA in sham group, but these results were not significantly different among three groups (p=0.597).
Conclusions—RIPC is safe in patients undergoing CAS, which may be able to decrease ischemic brain injury secondary to CAS. However, the mechanisms and effects of RIPC on clinical outcomes in this cohort of patients need further investigation.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654666
- Received August 6, 2016.
- Revision received December 19, 2016.
- Accepted January 26, 2017.