Albers, Gregory W.

Background Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI. Methods Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75–3.09; P -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33–2.12; P -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55–3.24; P -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07–3.69; P -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83–1.15; P -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6–83.6). Conclusions Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.

Background Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO. Methods Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0–3, and secondary outcomes included 90-day mRS score 0–2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0–3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001). Conclusions EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

Background Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke attributable to the anterior circulation large‐vessel occlusion. Randomized trials of patients with posterior circulation large‐vessel occlusion (PC‐LVO) have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta‐analysis to understand better whether EVT is beneficial for PC‐LVO. Methods Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC‐LVO treated with EVT versus MEDT. The primary outcome variable was 90‐day modified Rankin scale score of 0 to 3, and secondary outcome variables included 90‐day modified Rankin scale score of 0 to 2, 90‐day mortality, and rate of symptomatic intracranial hemorrhage. A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results Three studies with 1248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta‐analysis. The favorable outcome rate (modified Rankin scale score of 0–3) in patients undergoing EVT was 39.9% (95% CI, 30.6%–50.1%) versus 24.5% in patients undergoing MEDT (95% CI, 9.6%–49.8%). Patients undergoing EVT had higher modified Rankin scale score of 0 to 2 rates (31.8% [95% CI, 25.7%–38.5%] versus 19.7% [95% CI, 7.4%–42.7%]) and lower mortality (42.1% [95% CI, 35.9%–48.6%] versus 52.8% [95% CI, 33.3%–71.5%]) compared with patients undergoing MEDT, but neither result was statistically significant. Patients undergoing EVT were more likely to develop symptomatic intracranial hemorrhage (odds ratio, 10.36; 95% CI, 3.92–27.40). Conclusions EVT treatment of PC‐LVO trended toward superior functional outcomes and reduced mortality compared with MEDT despite a trend toward increased symptomatic intracranial hemorrhage in patients undergoing EVT. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in patients with PC‐LVO.

Background and Purpose: Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta-analysis to understand better whether EVT is beneficial for PC-LVO. Methods: Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC-LVO treated with EVT versus MEDT. The primary outcome variable was 90-day modified Rankin Scale (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results: Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MEDT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 rates (31.8% [95% CI: 25.7-38.5%] versus 19.7% [95% CI: 7.4-42.7%]) and lower mortality (42.1% [95% CI: 35.9-48.6%] versus 52.8% [95% CI: 33.3-71.5%]) compared to MEDT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40). Conclusions: EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MEDT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in PC-LVO patients.

Endovascular therapy with mechanical thrombectomy is a formidable treatment for severe acute ischemic stroke caused by occlusion of a proximal intracranial artery. Its strong beneficial effect is explained by the high rates of very good and excellent reperfusion achieved with current endovascular techniques. However, there is a sizable proportion of patients who do not experience clinical improvement despite successful recanalization of the occluded artery and reperfusion of the ischemic territory. Factors such as baseline reserve, collateral flow, anesthesia and systemic factors have been identified as potential culprits for lack of improvement in the setting of timely and successful revascularization. Older age, baseline disability and perhaps radiological markers of chronic brain injury can affect the prognosis of patients treated with endovascular therapy. Collateral flow is a major determinant of outcome after endovascular therapy and it is manifested by the size of the core in relation to the volume of the salvageable tissue. Parenchymal and vascular imaging can help assess the quality of collateral flow, but the optimal radiological strategy for daily practice (i.e. the optimal combination of rapid availability and diagnostic precision) has not been established. A sizable body of observational evidence indicates that acute hypertension, hyperglycemia and fever are associated with worse outcomes after a stroke even after optimal reperfusion with endovascular therapy. Lastly, current randomized controlled trials in anesthesia for stroke demonstrate similar rates of good functional outcome between general anesthesia and conscious sedation suggesting equipoise exists.

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

Background and Purpose— Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome. Methods— Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis. Results— Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT ( P =0.0006), even when corrected for age and initial stroke severity. Conclusion— The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

The recent “Advanced Neuroimaging for Acute Stroke Treatment” meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.