Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis.

BACKGROUND: Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use. METHODS AND RESULTS: A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration. CONCLUSIONS: Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Use of antiplatelet agents for prevention of ischemic stroke.

Overall management to lower risk for ischemic stroke is multifaceted. Management includes measures to treat risk factors for accelerated atherosclerosis and stroke, antithrombotic therapies to lower the risk for thromboembolism, and surgery to treat a defined arterial or cardiac lesion. Treatment decisions are made on a case-by-case basis, with most patients receiving some combination of medication and recommendations for lifestyle modification. Some patients will also undergo surgical or endovascular interventions. This article discusses antithrombotic treatment for ischemic stroke prevention, placing major emphasis on the indications for and administration of antiplatelet therapy.

Surgical results of the Carotid Occlusion Surgery Study.

OBJECT: The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion. A recent publication documented the methodology of the COSS in detail and briefly outlined the major findings of the trial. The surgical results of the COSS are described in detail in this report. METHODS: The COSS was a prospective, parallel-group, 1:1 randomized, open-label, blinded-adjudication treatment trial. Participants, who had angiographically demonstrated complete occlusion of the ICA causing either a transient ischemic attack or ischemic stroke within 120 days and hemodynamic cerebral ischemia indicated by an increased OEF measured by PET, were randomized to either surgical or medical treatment. One hundred ninety-five patients were randomized: 97 to the surgical group and 98 to the medical group. The surgical patients underwent an STA-MCA cortical branch anastomosis. RESULTS: In the intention-to-treat analysis, the 2-year rates for the primary end point were 21% for the surgical group and 22.7% for the medical group (p = 0.78, log-rank test). Fourteen (15%) of the 93 patients who had undergone an arterial bypass had a primary end point ipsilateral hemispheric stroke in the 30-day postoperative period, 12 within 2 days after surgery. The STA-MCA arterial bypass patency rate was 98% at the 30-day postoperative visit and 96% at the last follow-up examination. The STA-MCA arterial bypass markedly improved, although it did not normalize, the level of elevated OEF in the symptomatic cerebral hemisphere. Five surgically treated and 1 nonsurgically treated patients in the surgical group had a primary end point ipsilateral hemispheric stroke after the 30-day postoperative period. No baseline characteristics or intraoperative variables revealed those who would experience a procedure-related stroke. CONCLUSIONS: Despite excellent bypass graft patency and improved cerebral hemodynamics, STA-MCA anastomosis did not provide an overall benefit regarding ipsilateral 2-year stroke recurrence, mainly because of a much better than expected stroke recurrence rate (22.7%) in the medical group, but also because of a significant postoperative stroke rate (15%). Clinical trial registration no.: NCT00029146.

Investigating the mechanisms of perioperative ischemic stroke in the Carotid Occlusion Surgery Study.

OBJECT: The Carotid Occlusion Surgery Study (COSS) was a large, prospective clinical trial that examined whether superficial temporal artery-middle cerebral artery (STA-MCA) bypass, in addition to best medical therapy, reduced the risk of ipsilateral ischemic stroke in patients with carotid artery occlusion and hemodynamic cerebral ischemia. Despite improved cerebral hemodynamics and excellent bypass graft patency rates, COSS failed to show a benefit for the surgical group with respect to ipsilateral stroke recurrence at 2 years after treatment. This was due to a lower than expected rate of recurrent ipsilateral stroke in the medically treated group and a high rate of perioperative ipsilateral strokes in the surgical group. Critics of the trial have cited surgeon inexperience and technical difficulties related to the performance of the bypass graft as a leading cause of failure of the trial. METHODS: The authors retrospectively identified all patients from the COSS with an ipsilateral, perioperative (< 30 days) ischemic stroke after STA-MCA cortical branch anastomosis. Study records, operative notes, stroke adjudication forms, and imaging studies were reviewed. Ischemic strokes were characterized as bypass graft related or non-bypass graft related based on clinical and radiographic findings. RESULTS: Fourteen of 93 surgically treated patients experienced an ipsilateral, perioperative ischemic stroke. Postoperatively, the mean oxygen extraction fraction (OEF) ratio between the symptomatic and asymptomatic cerebral hemisphere significantly improved in these patients (1.30 ± 0.18 preoperative vs 1.12 ± 0.11 postoperative; p = 0.02), but did not normalize. In this cohort, total MCA occlusion time during the anastomosis (54.3 ± 23.5 minutes) was no different from the MCA occlusion time in those surgical patients who did not have a perioperative stroke (45.4 ± 24.2 minutes, p = 0.2). Bypass graft patency rates in patients with a perioperative stroke were 92% at 30 days (11 of 12 patients with patency data) and 83% at last follow-up visit (10 of 12 patients with patency data). These patency rates were not significantly different from those achieved at 30 days (100%; 76 of 76 patients with patency data; p = 0.14) and at last follow-up (99%; 71 of 72 patients with patency data; p = 0.052) in patients without a perioperative stroke. Eighty-six percent (12 of 14 patients) of strokes were likely attributable to factors unrelated to the STA-MCA anastomosis. Only 21% of strokes (3 of 14 patients) were in the territory of the recipient vessel and likely related to technical performance of the anastomosis itself. One patient was thought to have dual stroke mechanisms. CONCLUSIONS: Only a small minority of ipsilateral, perioperative ischemic strokes in the COSS could be attributed to technical problems of the bypass anastomosis. The majority of ischemic strokes could not be ascribed to this cause and were most likely due to patient hemodynamic fragility and the inability of patients to tolerate surgery.