Duration of Ischemia Affects Outcomes Independent of Infarct Size in Stroke.

BACKGROUND: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI). METHODS: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified treatment in cerebral infarction score 2b/3). FI was measured by Alberta Stroke Program Early CT score and volume on 24- to 48-hour computed tomography or magnetic resonance imaging. The likelihood of 90-day good functional outcome (modified Rankin scale 0-2) was assessed by OTR and absolute risk difference (ARD) was estimated using multivariable logistic regressions adjusting for patient characteristics including FI. RESULTS: In univariable analysis, longer OTR was associated with a decreased likelihood of good functional outcome (ARD -3% [95% CI -4.5 to -1.0]/h delay). In multivariable analysis accounting for FI, the association between OTR and functional outcome remained significant (ARD -2% [95% CI -3.5 to -0.4]/h delay) with similar ARD. This finding was maintained in the subset of patients with FI imaging using CT only, using Alberta Stroke Program Early CT Score or volumetric FI measurements, and also in patients with larger versus smaller FIs. CONCLUSIONS: The impact of OTR on outcomes appears to be mostly through a mechanism that is independent of FI. Our findings suggest that although the field has moved toward imaging infarct core definitions of eligibility for endovascular treatment, time remains an important predictor of outcome, independent of infarct core.

Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial.

IMPORTANCE: Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in symptomatic intracranial arterial stenosis. OBJECTIVE: To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%). DESIGN, SETTING, AND PATIENTS: VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013. INTERVENTIONS: Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53). PRIMARY OUTCOME MEASURE: a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12. RESULTS: Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (5/53; 9.4% [95% CI, 3.1%-20.7%]) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% [95% CI, 2.9%-19.0%]) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% [95% CI, 24.0-49.9]) vs the medical group (8/53; 15.1% [95% CI, 6.7-27.6]) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (6/53; 11.3% [95% CI, 4.3%-23.0%]) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up. CONCLUSIONS AND RELEVANCE: Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00816166.

Design of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial in symptomatic intracranial stenosis.

BACKGROUND: Patients with high-grade symptomatic intracranial stenosis (≥ 70%) have an increased risk of recurrent stroke despite medical treatment with antiplatelet or anticoagulant therapy. Intracranial stenting has been proposed as a viable treatment option for this high-risk patient population; however, evaluation of this therapy in randomized multicenter trials is needed. In this article, we present the design and methods of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial for symptomatic intracranial stenosis. METHODS: The VISSIT trial is a randomized control study designed to evaluate the safety, probable benefit, and effectiveness of the PHAROS Vitesse neurovascular balloon-expandable stent system plus medical therapy versus medical therapy alone in patients with cerebral or retinal ischemia due to neurovascular stenosis (≥ 70%) for preventing the primary composite end point: stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization or hard transient ischemic attack in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 postrandomization. RESULTS: Enrollment began in February 2009 and was halted in January 2012 with 112 subjects enrolled into the study. Clinical follow-up will continue for the planned period of 12 months postrandomization. CONCLUSIONS: The VISSIT trial may provide valuable insight into the use of balloon-expandable intracranial stent as a treatment option for high-risk patients. Lessons learned from this trial may better guide future clinical trial design on best patient selection, stenting techniques, and periprocedural management.