Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial

Rationale Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938

Antegrade or Retrograde Approach for the Management of Tandem Occlusions in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: Acute ischemic stroke (AIS) caused by tandem intracranial and extracranial occlusions is not rare. However, optimal strategy between antegrade (extracranial first) or retrograde (intracranial first) approaches still remains elusive. This systematic review and meta-analysis aim to compare the two approaches to provide updated clinical evidence of strategy selection.Methods: PubMed, Ovid, Web of Science, and the Cochrane Library were searched for literature comparing antegrade and retrograde approaches for patients with AIS with concomitant tandem occlusions. Outcomes including successful reperfusion [Throbolysis in Cerebral Infarction (TICI) 2b−3] and 90-day favorable outcome [modified Rankin Scale (mRS) 0–2], any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, procedural complications, and mortality were evaluated. The risk of bias was assessed using the Newcastle–Ottawa Scale and illustrated in the Funnel plot. Heterogeneity was assessed by I2 statistic. Subgroup and sensitivity analyses were also performed.Results: A total of 11 studies accounting 1,517 patients were included. 831 (55%) patients were treated with an antegrade approach and 686 (45%) patients were treated with the retrograde approach. A higher successful reperfusion rate was achieved in retrograde group than that of antegrade group [83.8 vs. 78.0%; odds ratio (OR): 0.63, 95% CI: 0.40–0.99, p = 0.04]. 90-day favorable outcome (mRS 0–2 at 90 days) also showed significantly higher in retrograde group compared with antegrade group (47.3 vs. 40.2%; OR: 0.72, 95% CI: 0.58–0.89, p = 0.002). The incidence of any intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage, 90-day mortality, and other complications did not differ between two groups.Conclusion: In AIS with tandem occlusions, the retrograde approach might achieve a higher successful reperfusion rate and better functional outcome with a comparable safety profile when compared with an antegrade approach. Further prospective controlled studies with more meticulous design and a higher level of evidence are needed to confirm these results.Systematic Review Registration: “PROSPERO” database (CRD 42020199093), https://www.crd.york.ac.uk/PROSPERO/.

Ventriculostomy-Related Intracranial Hemorrhage Following Surgical and Endovascular Treatment of Ruptured Aneurysms

Introduction : Endovascular therapy of ruptured aneurysms is regularly accompanied by periprocedural heparinization and requires the use of periprocedural antiplatelets in more complex cases. This raises concerns regarding increased bleeding risks in the case of frequently required ventriculostomy. The aim of this study was to analyze risk factors for ventriculostomy-related intracranial hemorrhages (VS-ICH) in endovascular or surgical treatment of ruptured aneurysms with a focus on antithrombotic therapy. Materials and Methods In this retrospective analysis we included patients admitted to our institution over a 12-year period who had received at least one ventriculostomy due to subarachnoid hemorrhage-related hydrocephalus. Patients were dichotomized into an endovascular and surgical group and rates of VS-ICH were compared. Risk factors for VS-ICH were assessed in uni- and multivariate analyses. Results A total of 606 ventriculostomies were performed in 328 patients. Within the endovascular group, antiplatelet therapy was used in 44.8% of cases. The overall rate of ventriculostomy-related intracranial hemorrhage was 13.1%. Endovascular treatment was associated with a higher rate of VS-ICH compared to surgical treatment (p=0.011), but not in cases without antiplatelet therapy (p=0.166). Application of any antiplatelet therapy (odds ratio, 2.647 [95% confidence interval, 1.141-6.143]) and number of ventriculostomies (odds ratio, 2.513 [95% confidence interval, 1.859-3.395]) were independent predictors of ventriculostomy-related hemorrhages. Discussion Our findings indicate an increased risk of VS-ICH in the endovascular group if administration of antiplatelets was required. While this aspect has to be included into treatment decision making, it must be weighed against the benefits of endovascular techniques.

Mechanical Thrombectomy in Patients with Acute Ischemic Stroke and Concomitant Intracranial Hemorrhage

Purpose Intravenous thrombolysis and mechanical thrombectomy (MT) are standard of care in patients with acute ischemic stroke due to large vessel occlusion. Data on MT in patients with intracranial hemorrhage prior to intervention is limited to anecdotal reports, as these patients were excluded from thrombectomy trials. Methods We analyzed patients from an observational multicenter cohort with acute ischemic stroke and endovascular treatment, the German Stroke Registry—Endovascular Treatment trial, with intracranial hemorrhage before MT. Baseline characteristics, procedural parameters and functional outcome at 90 days were analyzed and compared to a propensity score matched cohort. Results Out of 6635 patients, we identified 32 patients (0.5%) with acute ischemic stroke due to large vessel occlusion and preinterventional intracranial hemorrhage who underwent MT. Risk factors of intracranial hemorrhage were head trauma, oral anticoagulation and intravenous thrombolysis. Overall mortality was high (50%) but among patients with a premorbid modified Rankin scale (mRS) of 0–2 (n = 15), good clinical outcome (mRS 0–2) at 90 days was achieved in 40% of patients. Periprocedural and outcome results did not differ between patients with and without preinterventional intracranial hemorrhage. Conclusion Preinterventional intracranial hemorrhage in acute ischemic stroke patients with large vessel occlusion is rare. The use of MT is technically feasible and a substantial number of patients achieve good clinical outcome, indicating that MT should not be withheld in patients with preinterventional intracranial hemorrhage.

Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke

Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b–3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.