Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation.Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0–3 for transient ischemic attack (TIA), 3–5 for small-sized AIS (<1.5 cm), and 7–9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded.Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities].Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A).Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.
Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 hours post-AIS. Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with 6 studies (4 prospective open label treatment, blinded outcome studies and 2 randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (day 7–30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study-period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Results: We evaluated 509 patients; median infarct volume was 1.5 (0.1–7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0–3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50] P=0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 hours of onset was associated with similar recurrent ischemic event rates compared to those in which treatment was delayed (HR 0.42, [0.17 – 1.008] P=0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.84 – 16.24], p<0.001). Conclusions: In this pooled analysis, initiation of DOAC within 48 hours post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.
Introduction: Imprecise timing of symptom onset (SO) in patients with acute ischemic stroke (AIS) may impact eligibility for reperfusion therapy. Unreliable “last-known-well” (LKW) estimates may reduce the use of thrombolytic or endovascular treatments. A blood biomarker that serves as a “stroke clock” could minimize uncertainty and augment treatment rates. Methods: The single-center VuEssence Stroke Trial (VEST) evaluated gene expression biomarkers in adult ED patients with suspected AIS, a LKW time < 24hrs, and timing of SO accurate within a 0-3 hour time frame. At ED presentation and before reperfusion treatment, whole blood was collected in PAXgene RNA tubes for RNA-sequencing and gene expression analysis. Researchers blinded to molecular results adjudicated final diagnosis (AIS vs stroke mimic) and estimated time of SO based on times of witnessed onset (WO), LKW, and symptom discovery (SD). The confirmed AIS subgroup with WO timing, or ≤60 minutes between LKW and SD, was analyzed. Results: Of AIS patients, 56 met criteria (52% men, mean age 71.6). The average time from SO was 148 minutes (range 48-490). After RNA-sequencing, linear regression showed 684 genes with a significant linear time-related expression change in reference to time from SO (<0.2 Benjamini-Hochberg p-adjusted). A subgroup of 210 genes with <0.004 p-values and linear coefficients >0.25 were used to generate multiple classifiers of up to 12 genes that identified AIS <2.5 hrs from SO. Each gene is used in at least one classifier with other genes selected to maximize a measure of accuracy. The top panels showed both high sensitivity and specificity ( table ). Conclusion: Using a biological “stroke clock” biomarker instead of SO timing may streamline evaluations of suspected AIS, augment reperfusion therapy rates, and improve outcomes. VEST identified time-related gene expression changes that may accurately classify AIS <2.5 hrs from SO. These gene panels will require further validation.
Background: Despite the efficacy of Direct Oral Anticoagulants (DOACs) in Nonvalvular Atrial Fibrillation (NVAF), some patients may still develop an ischemic stroke while taking this medication. This can be from a primary efficacy problem, called DOAC “True failure” (due to drug absorption, metabolism, or clearance), or DOAC “Pseudo-failure” (due to alternate causes of stroke, not the NVAF). We aim to study the factors contributing to DOAC Pseudo-failures and isolate DOAC True Failure rates. Methods: IRB-approved, retrospective study of NVAF patients on DOAC who developed ischemic stroke between Jan 2012 and Dec 2017. Variables reviewed include DOAC Pseudo-failure causes listed in the mnemonic CHAMP: C for Compliance concerns (adherence [held for procedure, ran out, or discontinued], incorrect dose, or incorrect frequency [QD vs BID]); H for Hypertensive lacunar disease; A for Arterial diseases (such as Atherosclerosis [intra- or extra-cranial, carotid or vertebral arterial stenosis or dissection]); M for Malignant cancer or other hypercoagulable states; and P for Patent Foramen Ovale (PFO). Results: We identified 87 NVAF patients on DOAC who presented with ischemic stroke: 18 on Dabigatran, 37 on Apixaban and 32 on Rivaroxaban. Of those, 67 patients (77%) had at least one of the CHAMP variables (DOAC Pseudo-failure) while 20 (23%) were DOAC True failures. Compliance concerns were responsible for nearly half (49%) of the Pseudo-failures, followed by Malignancy/hypercoagulability (26%), Arterial disease (17%), HTN (5.7%) and PFO (2.3%). True Failure was lowest for Dabigatran (5.6%) followed by Apixaban (16%) and highest with Rivoraxaban (41%) despite its high compliance rate of 66%. Compliance for the BID DOACs (Dabigatran and Apixaban) were similar at 39 % and 43%, respectively. Conclusion: Patients on DOAC for NVAF who develop ischemic stroke are three times more likely to have another identifiable etiology. Compliance concerns, Cancer/Hypercoagulability, and arterial disease represent over 90% of DOAC Pseudo-failures. Thus, providers should educate patients on correct DOAC doses and frequencies, and screen presumed DOAC failures with scans of the chest, abdomen and pelvis in addition to intracranial and extracranial vessel imaging.
Background: Most stroke patients have their stroke in the community setting, however a significant minority occur while hospitalized for another condition. Prior studies have noted worse outcomes for in-hospital strokes(IHS) compared to community-onset strokes(COS). IHS are also less likely to receive intravenous thrombolytic therapy. The increased use of mechanical thrombectomy(MT) and distinct eligibility criteria from thrombolysis provide additional therapy options for these patients. We present one of the first comparison of outcomes looking specifically at MT for IHS versus COS. Methods: We performed an IRB-approved, retrospective cross-sectional study on patients who underwent MT at our center for acute ischemic stroke between Jan 2012 and Nov 2017. Variables reviewed included patient demographics, vascular risk factors, symptom recognition time, treatment time, and disability as measured by the Modified Rankin Scale(mRS). Statistical analyses were performed using logistic regression to assess the relationship between IHS versus COS. Results: We studied 334 patients (290 COS and 44 IHS) who were treated with MT for acute ischemic stroke. Patients who presented in-hospital were younger (60.7 vs. 70.4 years; p<0.001). IHS were more likely to have a history of coronary artery disease (48% vs. 25%; p<0.003) and tobacco use (32% vs. 16%; p<0.032), conversely, they had a lower rate of atrial fibrillation (20% vs. 42% p<0.005). No significant difference was noted in history of diabetes, hypertension, and dyslipidemia. IHS treated with MT had lower use of intravenous thrombolysis (14% vs 34%; p<0.006). Patients with IHS had a significantly shorter mean symptom recognition to femoral stick time (p<0.039). In addition, IHS patients had significantly better outcomes at discharge as measured by mRS 0-3 (mRS range, 0-6; lower scores indicating less disability). After adjustment for age and stroke severity (National Institute of Health Stroke Scale) IHS continued to have better outcomes at discharge as measured by mRS 0-3; AOR=4.832; 95% Cl, (1.207-19.348); P< 0.026. Conclusion: In conclusion, time from symptom recognition to MT is faster for IHS vs. COS. In addition, IHS had less disability after mechanical thrombectomy for large vessel occlusion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.