Background: and purpose In acute stroke patients, plasma concentrations of direct oral anticoagulants (DOAC) at hospital admission only poorly mirror DOAC exposure or the coagulation status at the time of the event. Here, we evaluated whether DOAC exposure and DOAC plasma concentration at the time of transient ischemic attacks (TIA) and ischemic strokes correlate with their likelihood of occurrence. Methods: Prospectively, consecutive DOAC patients with acute ischemic stroke or TIA were included. Admission DOAC plasma concentrations were measured by ultraperformance liquid chromatography– tandem mass spectrometry. Individual DOAC exposure (area under the curve) and DOAC concentrations at event onset were derived from population pharmacokinetic analyses. Results: DOAC exposure was successfully modeled in 211 patients (ischemic stroke 74.4%, TIA 25.6%). Compared to published values, 63.0% had relatively lower DOAC exposure and they more often received lower DOAC doses than recommended (odds ratio [OR], 2.125; 95% confidence interval [CI], 1.039 to 4.560; P=0.044). These patients more likely suffered ischemic strokes than TIA (OR, 2.411; 95% CI, 1.254 to 4.638; P=0.008) and their strokes were more severe (slope, 3.161; 95% CI, 0.741 to 5.58; P=0.011). Low relative DOAC concentrations at event onset were likewise associated with ischemic strokes (OR, 4.123; 95% CI, 1.834 to 9.268; P=0.001), but not to stroke severity (P=0.272). DOAC exposure had a higher explanatory value for stroke severity than concentrations at event. Conclusions Low DOAC exposure is strongly associated to ischemic stroke and its severity. By monitoring DOAC plasma concentrations, patients prone to ischemic stroke might be identified.

Background: and Purpose Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia. Methods: Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003–2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0–2) and death at 90 days. Results: Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02). Conclusions In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.

Background: and Purpose This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015–2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0–2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10–19] vs. 4 [2–7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24–1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28–18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group. Conclusion We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research.

Background: and Purpose We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0–4 and LVO who underwent EVT 6–24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0–2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2–4) and those without (mRS score 0–1). Results: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43–1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). Conclusion A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Background: and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.