In-stent restenosis (ISR) following intracranial artery stenting affects long-term clinical outcome. This randomized controlled trial sought to identify the long-term efficacy of exogenous tissue kallikrein (TK) for preventing ISR after intracranial stenting of symptomatic middle cerebral artery (MCA) atherosclerotic stenosis.Sixty-one patients successfully treated with intracranial stenting for symptomatic MCA M1 segment stenosis (>70%) were enrolled and randomized into 2 groups: control group and TK group. Patients in the TK group received human urinary kallidinogenase for 7 days, followed by maintenance therapy of pancreatic kallikrein for 6 months. The primary end point was angiographically verified ISR at 6 months, and secondary end points included vascular events and death within 12 months. Endogenous TK plasma concentrations of patients were measured before stenting and at the 6-month follow-up time-point.Patients in the TK group had lower occurrence rates of ISR and vascular events than patients in the control group. There was no difference in endogenous TK levels in plasma at 6 months postoperatively between the TK and control groups. Further subgroup analysis revealed that patients without ISR had higher endogenous TK levels at baseline and lower concentrations at 6 months postoperatively compared with patients who underwent ISR.Exogenous TK is effective for the prevention of ISR after intracranial stenting.
Trial registration: ClinicalTrials.gov NCT01558245.