Stent-retriever assisted vacuum-locked extraction (SAVE) versus a direct aspiration first pass technique (ADAPT) for acute stroke: data from the real-world.

BACKGROUND: Embolectomy is the standard of care in acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Aim of this study was to compare two techniques: A Direct Aspiration First Pass Technique (ADAPT) and Stent-retriever Assisted Vacuum-locked Extraction (SAVE) stratified by the occluded vessel. METHODS: One hundred seventy-one patients (71 male) treated between January 2014 and September 2017 with AIS due to LVO of the anterior circulation (55 carotid T, 94 M1, 22 M2) were included. Treatment techniques were divided into two categories: ADAPT and SAVE. Primary endpoints were successful reperfusion (mTICI ≥2b), near-perfect reperfusion (mTICI ≥2c) and groin puncture to reperfusion time. Secondary endpoints were the number of device-passes, first-pass reperfusion, the frequency of emboli to new territory (ENT), clinical outcome at 90 days, and the frequency of symptomatic intracranial hemorrhage (sICH). Analysis was performed on an intention to treat basis. RESULTS: Overall, SAVE resulted in significant higher rates of successful reperfusion (mTICI≥2b) compared to ADAPT (93.5% vs 75.0%; p = 0.006). After stratification for the occluded vessel only the carotid T remained significant with higher rates of near-perfect reperfusion (mTICI≥2c) (55.2% vs 15.4%; p = 0.025), while for successful reperfusion a trend remained (93.1% vs 65.4%; p = 0.10). Groin to reperfusion times were not significantly different. Secondary analysis revealed higher rates of first-pass successful reperfusion (59.6% vs 33.3%; p = 0.019), higher rates of first-pass near-perfect reperfusion in the carotid T (35.4% vs 16.7%; p = 0.038) and a lower number of device-passes overall (median 1 IQR 1-2 vs 2 IQR 2-3; p <  0.001) and in the carotid T (median 2 IQR 1.3 vs 3 IQR 2-5; p <  0.001) for SAVE. Clinical outcome and safety parameters were comparable between groups. CONCLUSIONS: Embolectomy using SAVE appears superior to ADAPT, especially for carotid T occlusions with regard to reperfusion success.

Robustness of testing procedures for confirmatory subpopulation analyses based on a continuous biomarker.

With the advent of personalized medicine, clinical trials studying treatment effects in subpopulations are receiving increasing attention. The objectives of such studies are, besides demonstrating a treatment effect in the overall population, to identify subpopulations, based on biomarkers, where the treatment has a beneficial effect. Continuous biomarkers are often dichotomized using a threshold to define two subpopulations with low and high biomarker levels. If there is insufficient information on the dependence structure of the outcome on the biomarker, several thresholds may be investigated. The nested structure of such subpopulations is similar to the structure in group sequential trials. Therefore, it has been proposed to use the corresponding critical boundaries to test such nested subpopulations. We show that for biomarkers with a prognostic effect that is not adjusted for in the statistical model, the variability of the outcome may vary across subpopulations which may lead to an inflation of the family-wise type 1 error rate. Using simulations we quantify the potential inflation of testing procedures based on group sequential designs. Furthermore, alternative hypotheses tests that control the family-wise type 1 error rate under minimal assumptions are proposed. The methodological approaches are illustrated by a trial in depression.