Zahra Ajani

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. METHODS In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). RESULTS Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone

Background and Purpose— Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods— THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System’s Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0–2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results— Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86–3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. Conclusions— THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy

Background and Purpose— Patients with acute ischemic stroke are at increased risk of developing parenchymal hemorrhage (PH), particularly in the setting of reperfusion therapies. We have developed a predictive model to examine the risk of PH using combined magnetic resonance perfusion and diffusion parameters, including cerebral blood volume (CBV), apparent diffusion coefficient, and microvascular permeability (K2). Methods— Voxel-based values of CBV, K2, and apparent diffusion coefficient from the ischemic core were obtained using pretreatment magnetic resonance imaging data from patients enrolled in the MR RESCUE clinical trial (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy). The associations between PH and extreme values of imaging parameters were assessed in univariate and multivariate analyses. Receiver-operating characteristic curve analysis was performed to determine the optimal parameter(s) and threshold for predicting PH. Results— In 83 patients included in this analysis, 20 developed PH. Univariate analysis showed significantly lower 10th percentile CBV and 10th percentile apparent diffusion coefficient values and significantly higher 90th percentile K2 values within the infarction core of patients with PH. Using classification tree analysis, the 10th percentile CBV at threshold of 0.47 and 90th percentile K2 at threshold of 0.28 resulted in overall predictive accuracy of 88.7%, sensitivity of 90.0%, and specificity of 87.3%, which was superior to any individual or combination of other classifiers. Conclusions— Our results suggest that combined 10th percentile CBV and 90th percentile K2 is an independent predictor of PH in patients with acute ischemic stroke with diagnostic accuracy superior to individual classifiers alone. This approach may allow risk stratification for patients undergoing reperfusion therapies. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT00389467.

Emergency Care of Patients with Acute Ischemic Stroke in the Kaiser Permanente Southern California Integrated Health System.

CONTEXT Tissue plasminogen activator (tPA) is underutilized for treatment of acute ischemic stroke. OBJECTIVE To determine whether the probability of tPA administration for patients with ischemic stroke in an integrated health care system improved from 2009 to 2013, and to identify predictors of tPA administration. DESIGN Retrospective analysis of all ischemic stroke presentations to 14 Emergency Departments between 2009 and 2013. A generalized linear mixed-effects model identified patient and hospital predictors of tPA. MAIN OUTCOME MEASURES Primary outcome was tPA administration; secondary outcomes were door-to-imaging and door-to-needle times and tPA-related bleeding complications. RESULTS Of the 11,630 patients, 3.9% received tPA. The likelihood of tPA administration increased with presentation in 2012 and 2013 (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.26-2.43; and OR = 2.58; 95% CI = 1.90-3.51), female sex (OR = 1.27; 95% CI = 1.04-1.54), and ambulance arrival (OR = 2.17; 95% CI = 1.76-2.67), and decreased with prior stroke (OR = 0.47; 95% CI = 0.25-0.89) and increased age (OR = 0.98; 95% CI = 0.97-0.99). Likelihood varied by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA-treated patients, median door-to-imaging time was 15 minutes (interquartile range, 9-23 minutes), and door-to-needle time was 73 minutes (interquartile range, 55-103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9% among tPA- and non-tPA treated patients (p < 0.001). CONCLUSION Acute ischemic stroke care improved over time in this integrated health system. Better understanding of differences in hospital performance will have important quality-improvement and policy implications.