Abstract P713: Early Apixaban Therapy After Ischemic Stroke in Patients With Atrial Fibrillation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Anas Alrohimi ◽  
Brian H Buck ◽  
Glen Jickling ◽  
Ashfaq Shuaib ◽  
Sibi Thirunavukkarasu ◽  
...  

Background: The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. Patients and methods: A prospective, open label study (NCT04435418) of patients with AF treated with apixaban within 14 days of ischemic stroke/TIA onset was conducted. Baseline and follow-up CT scans were assessed for hemorrhagic transformation (HT) and graded using European Cooperative Acute Stroke Study (ECASS) criteria. The primary endpoint was symptomatic HT. Incident HT rates were assessed as Objective Performance Criteria. Results: One-hundred AF stroke patients, with a mean age of 79±11 years were enrolled. Median infarct volume was 4 (0.5-10.75) ml. Median time from index event onset to apixaban initiation was 2 (1-6) days, and median baseline NIHSS was 4 (1-9). Asymptomatic HT on baseline imaging was present in 15 patients. Infarct volume (OR= 1.1, [1.02-1.12], P <0.0001) and NIHSS (OR= 1.11, [1.03-1.20], P =0.007) were both associated with baseline HT. No patients developed symptomatic HT or systemic hemorrhage. Incident asymptomatic HT was seen on follow-up CT scan in 3 patients. Patients with incident HT were functionally independent (mRS=0-2) at 90 days. Recurrent ischemic events occurred within 90 days in 13 patients, 4 of which were associated with severe disability (mRS 3-5) and 4 with death. Discussion: Early apixaban treatment did not precipitate symptomatic HT after stroke. All HT was asymptomatic identified on imaging. Recurrent ischemic events were common and clinically symptomatic. Conclusions: Symptomatic HT rates are likely to be low in randomized trials of DOAC initiation post-stroke. Recurrent ischemic stroke may be the major clinical outcome.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
H. B Brouwers ◽  
Svetlana Lorenzano ◽  
Lyndsey H Starks ◽  
David M Greer ◽  
Steven K Feske ◽  
...  

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.


Author(s):  
Anas Alrohimi ◽  
Kelvin Ng ◽  
Dar Dowlatshahi ◽  
Brian Buck ◽  
Grant Stotts ◽  
...  

ABSTRACT:Objectives:The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients.Patients and Methods:A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria.Results:One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020–1.107], p < 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0–2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively).Conclusion:Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.


2020 ◽  
Vol 49 (6) ◽  
pp. 619-624
Author(s):  
Keisuke Tokunaga ◽  
Masatoshi Koga ◽  
Sohei Yoshimura ◽  
Yasushi Okada ◽  
Hiroshi Yamagami ◽  
...  

<b><i>Background:</i></b> The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). <b><i>Methods:</i></b> Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. <b><i>Results:</i></b> A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). <b><i>Conclusion:</i></b> Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Andrew B Buletko ◽  
Rejo P Cherian ◽  
Christine Ahrens ◽  
Ken Uchino ◽  
Andrew Russman

Introduction: Uncertainty exists as to the optimum interval for initiation of oral anticoagulation (OAC) after an acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). Randomized clinical trials of novel oral anticoagulants excluded patients with AIS within 7-14 days. We sought to identify patients at low risk for early initiation of OAC after AIS. Hypothesis: The benefit of starting OAC within 2 days to prevent recurrent AIS outweighs the risk of hemorrhagic transformation (HT) in select patients. Methods: Following IRB approval, we completed a retrospective review of patients from the Cleveland Clinic from 2012-2014 with AIS, AF, and at least 1 follow up visit. In addition to demographic and medical history, acute infarct volume on imaging, presence of HT on imaging prior to OAC, timing and type of oral anticoagulation, and ischemic and hemorrhagic complications were noted. Early OAC was defined as starting within 48 hours after stroke onset, and late OAC was thereafter. The two groups were compared using Fisher’s exact test for categorical and Wilcoxon Rank Sum for numeric variables. Results: One hundred patients (median age 76, interquartile range 66-84) met our study criteria. Thirty-one patients were started on OAC within 2 days vs 53 patients after 2 days (median 1 days vs median 11 days). Compared to patients started on OAC after 2 days, those who initiated OAC within 2 days had significantly lower infarct volume (median 3.35 ml vs median 9.8 ml; p<0.0001), initial NIHSS (median 3 vs median 7; p <0.0001), and fewer people with blood on brain imaging (3% vs 26%; p= 0.0074). Age, prior stroke, and choice of OAC were not significantly associated with timing of OAC. No patients had recurrent AIS or symptomatic HT at median follow-up observation of 37 days. One patient had a non-CNS major hemorrhage after starting OAC. Sixteen patients were not started on OAC for a variety of reasons. Conclusions: Our results suggest the safety of early initiation of OAC with 2 days in an appropriately selected population of patients with AIS, who have small infarct volumes, mild stroke severity, and lack of HT.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Danny J Wang ◽  
Nerses Sanossian ◽  
Albert K Fong ◽  
Qing Hao ◽  
...  

Background: Arterial spin-labeled (ASL) MRI facilitates repeated noninvasive evaluation of cerebral blood flow without the use of contrast. Hyperperfusion may be readily detected with ASL and serial imaging may therefore chronicle the dynamics of territorial perfusion from acute to chronic phases after stroke. We characterized hyperperfusion on ASL in a prospective series of acute ischemic stroke patients, describing the clinical correlates, time course and association with reperfusion hemorrhage. Methods: A consecutive series of acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL with background suppressed 3D GRASE (delay=2s, matrix=64x64; 26 slices, resolution 3.4x3.4x5mm, scan time 4min). Post-processed ASL CBF maps were visually inspected for detection of hyperperfusion. DSA measures of collaterals and reperfusion were scored when available and hemorrhagic transformation (HT) was graded on GRE in all 198 cases. Univariate and multivariate statistical analyses delineated clinical correlates, timing and other imaging features of hyperperfusion. Results: Among 198 patients, mean age was 69.4±15.7 years and 48.5% were women. Among 77 with serial ASL MRI, interval from initial to follow-up MRI was median 25.0 (IQR 10.3-53.9) hours. Hyperperfusion was detected in 15/198 (7.6%) patients at baseline and 30/77 (39.0%) at follow-up. Trajectories included 7/77 (9.1%) with hyperperfusion at both baseline and follow-up and 38/77 (49.4%) showing hyperperfusion at any timepoint during admission. Hyperperfusion correlated with achievement of reperfusion among patients undergoing endovascular therapy (OR 6.5, 95% CI 1.82-23.25, p=0.018) and history of atrial fibrillation (OR 4.4, 95% CI 1.9-10.6, p<0.001). Analysis of the 42 cases with DSA revealed that hyperperfusion was most common in patients with poor collateral grade followed by more complete TICI reperfusion scores. Overall, HT affected 57/198 (28.8%), including 35/198 (17.7%) HI1, 11/198 (5.6%) HI2, 8/198 (4.1%) PH1 and 3/198 (1.5%) PH2. Multivariate analyses revealed that hyperperfusion at any timepoint was a potent predictor of HT (OR 52.6, 95%CI 12.4-222.6, p<0.001). Conclusions: Hyperperfusion in acute ischemic stroke is frequently demonstrated by ASL MRI, providing novel insight on the dynamics of reperfusion and HT. Hyperperfusion increases the risk of HT 50-fold, likely due to autoregulatory loss. Poor collaterals and sudden reperfusion in vulnerable cases such as those with atrial fibrillation may herald hyperperfusion and HT.


2019 ◽  
Vol 14 (9) ◽  
pp. 946-955 ◽  
Author(s):  
Inge A Mulder ◽  
Ghislaine Holswilder ◽  
Marianne AA van Walderveen ◽  
Irene C van der Schaaf ◽  
Edwin Bennink ◽  
...  

Background Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. Methods We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion <9 h of onset and follow-up CT after three days. On admission, presence of a perfusion deficit, infarct core and penumbra volume, and blood brain barrier permeability (BBBP) were assessed. At follow-up we assessed malignant edema, hemorrhagic transformation, and final infarct volume. Outcome at three months was evaluated with the modified Rankin Scale (mRS). We calculated adjusted relative risks (aRR) or difference of means (aB) with regression analyses. Results We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77–1.25), infarct core volume (aB: -10.8, 95%CI: -27.04–5.51), penumbra volume (aB: -11.6, 95%CI: -26.52–3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11–2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04–1.73), final infarct volume (aB: -14.8, 95%CI: 29.9–0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21–1.22). Conclusion Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Katinka R van Kranendonk ◽  
Manon Kappelhof ◽  
Vicky Chalos ◽  
Kilian M Treurniet ◽  
Wim van Zwam ◽  
...  

Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural progression or as a complication of treatment with potential subsequent neurological deterioration. Currently it is unclear whether these hemorrhagic transformations (HT) contribute to the poorer functional outcomes observed in patients with large infarcts. The purpose of this study is to assess the association of HT with follow-up infarct volume (FIV) and functional outcome at 90 days after AIS. Additionally, we determined whether the development of HT was associated with a diminished endovascular therapy (EVT) effect. Methods: All patients from the HERMES collaboration with follow-up imaging were included. HERMES is pooled data from seven randomized controlled trials that assessed the efficacy and safety of EVT compared to usual care. Patients with HT were identified according to the ECASS classification and FIV was assessed on CT or MRI. Infarct and hemorrhage were included in the FIV. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with adjustment for potential confounders was used to determine the association of HT and FIV with functional outcome. Results: Of all included patients with follow-up imaging (n=1665), 42% had HT (n=698). Before and after adjustment for confounders HT and FIV were associated with a shift in the direction of poorer functional outcome (aOR:0.71,95%CI:0.58-0.86 and aOR:0.99,95%CI:0.99-0.99). EVT was beneficial in patients with and without HT, but effect was greater in patients without (aOR:1.70,95%CI:1.27-2.28 vs. aOR:2.51,95%CI:1.97-3.20)(figure 1.) Conclusions: In this analysis, patients with HT after AIS were less likely to have good functional outcome compared to those without HT, independent of the FIV. While the EVT effect was slightly diminished in patients who developed HT, EVT was always of significant benefit.


Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam de Havenon ◽  
Christopher R. Leon Guerrero ◽  
Amre Nouh ◽  
...  

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Ken Butcher ◽  
Mahesh Kate ◽  
Laura Gioia ◽  
Tom Jeerakathil ◽  
Brian Buck ◽  
...  

Introduction: Transient Ischemic Attack (TIA) and Minor ischemic stroke (MIS) patients are at high risk for recurrent events. Older anticoagulants are associated with a reduction in recurrent events, but also an increase in hemorrhagic transformation (HT). Dabigatran etexilate (DE), a novel oral anticoagulant that is associated with reduced risk of intracranial bleeding in atrial fibrillation (AF) patients, may be an effective therapy in this population. DE is not indicated within 14 days of ischemic stroke, due to an absence of data. We tested the feasibility and safety of initiating DE therapy within 24 h of TIA/MIS. Methods: We designed a 50 patient single arm open label treatment trial. The primary endpoint was symptomatic HT within 30 days of enrolment. All patients underwent MRI prior to treatment. TIA/MIS patients (NIHSS score ≤3) with a DWI lesion were prospectively treated with DE 150 mg BID (110 mg BID in patients ≥ 80 or if CrCl <40 ml/min). Treatment began within 24 h of onset and continued for 30 days. Patients with known atrial fibrillation (AF) were excluded. Patients were re-imaged at day 7 and 30, with clinical assessment to 90 days. Results: Forty-three of 50 patients have been enrolled to date (March 2012-August 2013). The mean age was 66±12 years and median (IQR) NIHSS was 1 (2). Median baseline DWI volume was 0.89(1.9) ml. The median time from onset to initial DE dose was 18.5 (12.2) h. Therapy was completed in 41 patients and discontinued in two (withdrawal of consent (1) and dysphagia (1)). Two patients died within the 90 day study period, both after completion of DE therapy. No patients experienced systemic bleeding or symptomatic intracranial hemorrhage. One patient had asymptomatic HT (ECASS grade, HI1) on day 7, which resolved by day 30 despite continuing DE. No patients experienced recurrent clinical stroke. New asymptomatic DWI lesions developed in 7 (16%) patients by day 30. Conclusion: These preliminary data suggest DE may be used safely in acute TIA/MIS patients and larger randomized trials are warranted. The low HT rate may make DE an ideal antithrombotic for use immediately after TIA/ischemic stroke.


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