| 1. |
- Altavilla, R., et al.
(författare)
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Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin?
- 2019
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:8, s. 2093-2100
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
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| 2. |
- Fischer, U., et al.
(författare)
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Early versus Later Anticoagulation for Stroke with Atrial Fibrillation
- 2023
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 388:26, s. 2411-2421
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.MethodsWe performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.ResultsOf 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.ConclusionsIn this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, .)
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| 3. |
- Giustozzi, M., et al.
(författare)
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Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
- 2020
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Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
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| 4. |
- Hart, R. G., et al.
(författare)
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Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
- 2018
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 378:23, s. 2191-2201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.
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| 5. |
- Martinez-Majander, N., et al.
(författare)
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Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial
- 2020
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:5, s. 841-848
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. Methods Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. Results Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. Conclusions Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. (NCT02313909).
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| 6. |
- Ntaios, G., et al.
(författare)
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Age- and sex-specific analysis of patients with embolic stroke of undetermined source
- 2017
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 89:6, s. 532-539
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS). Methods: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS InternationalWorking Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death. Results: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those.80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60-to 80-and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p, 0.001) and death (6.4%, 40.6%, and 100%, respectively, p, 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively). Conclusions: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is approximate to 3-and 8-fold higher in patients >80 years compared with those <[60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.
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| 7. |
- Ntaios, G., et al.
(författare)
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Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source
- 2018
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 49:12, s. 2904-2909
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods-We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results-In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR >= 90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions-The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.
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| 8. |
- Ntaios, G., et al.
(författare)
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Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source
- 2016
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Ingår i: Stroke. - 0039-2499. ; 47:9, s. 2278-2285
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS 2) and CHA 2 DS 2 -VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS. Methods - We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS 2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA 2 DS 2 -VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS 2 and CHA 2 DS 2 -VASc scores. Results - One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS 2 score 0, patients with CHADS 2 score 1 and CHADS 2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86-10.40, respectively). Compared with low-risk CHA 2 DS 2 -VASc score, patients with high-risk CHA 2 DS 2 -VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4). Conclusions - The risk of recurrent ischemic stroke/TIA and death in ESUS is reliably stratified by CHADS 2 and CHA 2 DS 2 -VASc scores. Compared with the low-risk group, patients in the high-risk CHA 2 DS 2 -VASc group have much higher risk of ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold, respectively. © 2016 American Heart Association, Inc.
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| 9. |
- Ntaios, G, et al.
(författare)
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Small-vessel occlusion versus large-artery atherosclerotic strokes in diabetics: Patient characteristics, outcomes, and predictors of stroke mechanism
- 2016
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 1:2, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Introduction: Diabetes mellitus exerts a detrimental effect on cerebral vasculature affecting both macrovasculature and microvasculature. However, although ischaemic stroke is typically included among macrovascular diabetic complications, it is frequently omitted from microvascular diabetic complications. We aimed to compare the proportion of large-artery atherosclerotic and small-vessel occlusion strokes among diabetic stroke patients, explore their differences and outcomes, and assess potential mechanisms which may determine why some diabetic patients suffer large-artery atherosclerotic stroke whereas others suffer small-vessel occlusion stroke. Methods: We pooled data of diabetic patients from four prospective ischaemic stroke registries (Acute Stroke Registry and Analysis of Lausanne (ASTRAL), Athens, Austrian, and Helsinki Stroke Thrombolysis Registries). Stroke severity and prognosis were assessed with National Institutes of Health Stroke Scale (NIHSS) and ASTRAL scores, respectively; functional outcome with three-month modified Rankin score (0–2 considered as favourable outcome). Logistic- regression analysis identified independent predictors of large-artery atherosclerotic stroke. Results: Among 5412 patients, 1069 (19.8%) were diabetics; of them, 232 (21.7%) had large-artery atherosclerotic and 205 (19.2%) small-vessel occlusion strokes. Large-artery atherosclerotic stroke had higher severity than small-vessel occlusion stroke (median NIHSS: 6 vs. 3, p < 0.001), worse prognosis (median ASTRAL score: 23 vs. 19, p < 0.001), and worse three-month outcome (60.3% vs. 83.4% with favourable outcome, p < 0.001). In logistic-regression analysis, peripheral artery disease (odds ratio: 4.013, 95% confidence interval: 1.667–9.665, p < 0.01) and smoking (odds ratio: 1.706, 95% confidence interval: 1.087–2.675, p < 0.05) were independently associated with large-artery atherosclerotic strokes. Conclusion: In the diabetic stroke population, small-vessel occlusion and large-artery atherosclerotic strokes occur with similar frequency. Large-artery atherosclerotic strokes are more severe and have worse outcome than small-vessel occlusion strokes. The presence of peripheral artery disease and smoking independently predicted large-artery athero- sclerotic stroke.
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| 10. |
- Paciaroni, M., et al.
(författare)
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Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study
- 2017
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Background-The 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 theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence 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. Conclusions-In 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.
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