Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P <0.001); intracerebral hemorrhages decreased from 400 to 322 (hospitalization RR, 0.81 [95% CI, 0.69–0.93]; P =0.004), and transient ischemic attacks decreased from 322 to 196 (hospitalization RR, 0.61 [95% CI, 0.51–0.73]; P <0.001). Hospitalizations decreased in Northern, Central, and Southern Italy. Intravenous thrombolyses decreased from 531 (22.1%) in 2019 to 345 in 2020 (19.1%; RR, 0.86 [95% CI, 0.75–0.99]; P =0.032), while primary endovascular procedures increased in Northern Italy (RR, 1.61 [95% CI, 1.13–2.32]; P =0.008). We found no correlation ( P =0.517) between the hospitalization RRs for all strokes or transient ischemic attack and COVID-19 incidence in the different areas. Conclusions: Hospitalizations for stroke or transient ischemic attacks across Italy were reduced during the worst period of the COVID-19 outbreak. Intravenous thrombolytic treatments also decreased, while endovascular treatments remained unchanged and even increased in the area of maximum expression of the outbreak. Limited hospitalization of the less severe patients and delays in hospital admission, due to overcharge of the emergency system by COVID-19 patients, may explain these data.

BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Eligible were patients admitted for thrombolysis in 14 Italian centers and were registered in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), according to SITS-Monitoring Study criteria. 6 Study protocol was approved from each ethical committee, and all patients gave informed consent.Background and Purpose-Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods-We measured MMPs 1, 2, 3,7,8, 9, and Blood samples were taken before and 24 hours after tPA. Outcomes were defined as follows: (1) symptomatic intracerebral hemorrhage (SICH), using the National Institute of Neurological Disorders and Stroke criteria; 7 (2) 3-month death; (3) modified Rankin disability score, dichotomized into good (modified Rankin scale, 0-2) or poor (modified Rankin scale, 3-6) outcome. As a main explanatory variable, we used single patient's relative pre-and post-thrombolysis variation (Δ median value) of both MMPs and TIMPs levels, calculated according to the formula: (24-hour post-tPA MMP or TIMP-pre-tPA MMP or TIMP)/pre-tPA MMP or TIMP. Differences in these Δ values were analyzed in relation to demographic and clinical features and across subgroups of patients with different outcomes. Methods details are in the online-only Data Supplement. ResultsBetween October 2008 and June 2011, 534 patients were registered in the SITS-ISTR, of whom 327 (mean age, 68.9±12.1 years; 58% males) were investigated. The remaining 207 were not studied because of not fulfilling SITS-MOST criteria, not giving consent, blood samples not taken or not stored appropriately, outcomes not assessed, and other protocol violations. Except for onset-to-treatment time, the prevalence of major outcomes determinants did not differ significantly between the 2 groups (demographics and clinical characteristics of both groups are in Table I in the online-only Data Supplement).Absolute TIMPs or MMPs measures taken before thrombolysis and 24 hours after are reported in the Table II in the online-only Data Supplement.The Figure shows pre-and post-thrombolysis changes of each MMP and TIMP level measured in patients with and without SICH, in patients who died and in those who survived, and in patients scoring 3 to 6 or 0 to 2 on the 3-month modified Rankin scale. MMP9, TIMP4, and MMP2 level changes showed a tendency toward the association with SICH. Variations of MMP8, MMP9, and TIMP1 levels were significantly associated with death, whereas variations of MMP8, MMP9, and TIMP4 levels were associated with scoring 3 to 6 on the 3-month modified Rankin scale. Grading of hemorrhage severity (according to the European Cooperative Acute Stroke Study II criteria) in the 27 patients with SICH is shown in Table III in the online-only Data Supplement. The association of MMP9 level variation with he...

Background and Purpose-The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods-ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke