Remote Ischemic Post-Conditioning Shows Significant Benefit With IVT

October 12, 2020

Investigators noted changes in plasma vascular endothelial growth factor and S100 ß levels indicate a protection-based mechanism derived from the combined treatment.

Results from a single-center, randomized, controlled trial (NCT03218293) of patients with acute ischemic stroke (AIS) revealed that administration of repeated remote ischemic post-conditioning (RIPC) after intravenous thrombolysis (IVT) can significantly facilitate the recovery of nerve function and improve clinical prognosis.

Investigators found that an excellent recovery, measured as modified Rankin Scale (mRS) scores of 0–1, was observed in 71.9% of patients at 3 months in the RIPC group compared to 50.0% in the control group (adjusted risk ratio, 9.85; 95% CI, 1.54–63.16; P = .016).

Senior author Guo-gang Luo, MD, PhD, department of neurology, the First Affiliated Hospital of Xi’an Jiaotong University, China, and colleagues assessed 34 patients in both the RIPC and control groups on the primary end point of mRS scores of 0 or 1 at Day 90, as well as the safety, tolerability and neuroprotection biomarkers associated with RIPC.

In addition to greater clinical outcome, patients in the RIPC group had significantly lower plasma S100 ß (P = .007) and higher vascular endothelial growth factor (VEGF; P = .003) levels than in controls. No significant changes were identified for MMP9, BDNF, bFGF or HO1. Luo and colleagues added that “in the brain, VEGFs play a positive role in angiogenesis, neuroprotection and neurogenesis, but can cause edema and the subsequently elevated intracranial pressure within 24 hours after stroke onset.”

Luo et al also noted that treatment with alteplase combined with RIPC contributed to a more favorable outcome than that with alteplase alone, as well as for the secondary end points with an at least 6-point improvement in the National Institutes of Health Stroke Scale (NIHSS) score at 90 days.

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In total, the average duration of hospitalization was 11.2 days and there were no documented significant differences between the 2 groups at admission for NIHSS score (P = .364) or time to treatment administration (P = .889).

Additional treatment with RIPC did produce a significant increase in the proportion of patients with independent recovery, shown as mRS score of 0 to 2, at 3 months (control: 58.8%; RIPC: 81.3%; adjusted P value = .020) and a 6-point improvement on the NIHSS at 90 days (control: 41.9%; RIPC: 16.1%; adjusted P value = .035). Notably, there were no significant differences between the groups in regard to other functional outcomes such as NIHSS score 0 or 1 at discharge, Barthel index ≥95 at discharge, or NIHSS score 0 or 1 at Day 90.

Investigators documented that patients tolerated the inflation process well and no skin or vessel lesions were observed during a 10-day study period. One patient developed skin redness without further sequelae, and another was uncomfortable with the pressure procedure.

There were no significant differences between the RIPC group and control group in terms of mortality within 3 months. Three patients in the control group died at Day 3, Day 6 and Day 48 due to the severity of stroke and included comorbidities such as hemorrhagic transformation, cerebral hernia, and large cerebral infarction.

Early neurological deterioration (END) was found in 1 subject in the RIPC group and 2 in the control group. In the presence of the incidence of symptomatic hemorrhagic transformation (sICH), there was no difference between the 2 groups.

"Our study indicates that AIS patients are more likely to obtain a favorable clinical outcome after IV tPA and repeated RIPC than patients only receiving IV tPA therapy,” the study investigators concluded. “Thus, the efficacy and safety of RIPC therapy in patients suffering from thrombectomy should be further investigated.”

REFERENCE
An JQ, Cheng Y, Guo Y, et al. Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke. Neurology. Published online October 7, 2020. doi: 10.1212/WNL.0000000000010884