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INTRODUCTION: Cervical artery dissection (CeAD) is considered a non-atherosclerotic arteriopathy, but atherosclerosis of the cervical arteries may co-exist. We explored the frequency and clinical importance of co-existent atherosclerosis in patients with CeAD. PATIENTS AND METHODS: Single-center exploratory study from the Stroke Center Basel, Switzerland. We re-reviewed duplex ultrasound images at (i) baseline and (ii) last follow-up visit for the presence versus absence of the following atherosclerotic manifestations in the carotid arteries: (i) abnormal carotid intima-media thickness, (ii) plaques, and (iii) atherosclerotic stenosis. We investigated whether CeAD patients with versus without co-existing atherosclerosis differ regarding (a) recurrence of CeAD and (b) occurrence of vascular events (myocardial infarction, peripheral artery disease, or ischemic stroke) using logistic regression with adjustment for age and follow-up time. RESULTS: Among 294 CeAD patients (median age 46 [IQR 37-53], 41.8% women), 35 (12%) had any atherosclerotic signs at baseline. Among 196 patients with available follow-up, another 21/196 (11%) patients developed atherosclerosis during a median follow-up of 55.7 months. Patients with atherosclerosis had decreased odds of recurrent CeADs when compared to patients without atherosclerosis (OR 0.03, 95% CI = 0.00-0.30). During follow-up, 6 (15%) vascular events occurred among 40 CeAD patients with atherosclerosis and 13 (8.5%) among 153 patients without atherosclerosis (OR 1.38, 95% CI = 0.39-4.55, data for 3 patients were missing). DISCUSSION AND CONCLUSION: Signs of atherosclerosis in the carotid artery were detectable in 12% of CeAD patient at baseline. Additionally, 11% of CeAD patients developed new signs of atherosclerosis within the following 5 years. The presence of atherosclerosis may suggest a lower risk for recurrent CeAD. Whether it might indicate an increased risk for late clinical vascular events deserves further studies.
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INTRODUCTION: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results. PATIENTS AND METHODS: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows. RESULTS: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3. DISCUSSION AND CONCLUSION: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective.
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[This corrects the article DOI: 10.3389/fneur.2022.1024891.].
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PURPOSE: Lower extremity physical function (LEPF) is a key component for mobility and is impacted in stroke-related disability. A reduction in LEPF can have a significant impact on an individual's Quality of Life (QoL). The aim of this study is to characterise the relationship between LEPF and QoL. METHODS: The MOBITEC-Stroke Study is a longitudinal cohort-study including patients with their first occurrence of ischaemic stroke. Using a linear mixed-effects model, the relationship between LEPF (timed up-and-go performance (TUG); predictor) and QoL (Stroke Specific Quality of Life scale (SS-QoL); outcome) at 3 and 12 months post stroke was investigated and adjusted for sex, age, Instrumental Activities of Daily Living (IADL), fear of falling (Falls Efficacy Scale-International Version, FES-I), and stroke severity (National Institute of Stroke Severity scale, NIHSS), accounting for the repeated measurements. RESULTS: Data of 51 patients (65 % males, 35% females) were analysed. The mean age was 71.1 (SD 10.4) years, median NIHSS score was 2.0. SS-QoL was 201.5 (SD 20.5) at 3 months and 204.2 (SD 17.4) at 12 months; the mean change was 2.7 (95% CI -2.4 to 7.7), p= 0.293. A positive association was found between baseline TUG performance (estimate log score -13.923; 95% CI -27.495 to -0.351; p=0.048) and change in SS-QoL score in multivariate regression analysis. CONCLUSION: Higher LEPF (i.e better TUG performance) at baseline, was associated with an improvement in QoL from 3- to 12-months post stroke. These results highlight the critical role of physical function, particularly baseline LEPF, in influencing the QoL of stroke survivors.
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BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.
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Anticoagulantes , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Disección de la Arteria Vertebral/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Disección de la Arteria Carótida Interna/tratamiento farmacológicoRESUMEN
RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.
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Importance: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. Objective: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. Data Sources: PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. Study Selection: Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. Data Extraction/Synthesis: Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. Main Outcomes and Measures: The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. Results: Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). Conclusions and Relevance: This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.
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Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Disección de la Arteria Vertebral , Humanos , Disección de la Arteria Vertebral/tratamiento farmacológico , Disección de la Arteria Vertebral/complicaciones , Fibrinolíticos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Disección de la Arteria Carótida Interna/tratamiento farmacológicoRESUMEN
Introduction: The Fugl-Meyer Motor Assessment (FMMA) is recommended for evaluating stroke motor recovery in clinical practice and research. However, its widespread use requires refined reliability data, particularly across different health professions. We therefore investigated the interrater reliability of the FMMA scored by a physical therapist and a physician using video recordings of stroke patients. Methods: The FMMA videos of 50 individuals 3 months post stroke (28 females, mean age 71.64 years, median National Institutes of Health Stroke Scale score 3.00) participating in the ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial) were independently scored by two experienced assessors (i.e., a physical therapist and a physician) with specific training to ensure consistency. As primary endpoint, the interrater reliability was calculated for the total scores of the entire FMMA and the total scores of the FMMA for the upper and lower extremities using intraclass correlation coefficients (ICC). In addition, Spearman's rank order correlation coefficients (Spearman's rho) were calculated for the total score and subscale levels. Secondary endpoints included the FMMA item scores using percentage agreement, weighted Cohen's kappa coefficients, and Gwet's AC1/AC2 coefficients. Results: ICCs were 0.98 (95% confidence intervals (CI) 0.96-0.99) for the total scores of the entire FMMA, 0.98 (95% CI 0.96-0.99) for the total scores of the FMMA for the upper extremity, and 0.85 (95% CI 0.70-0.92) for the total scores of the FMMA for the lower extremity. Spearman's rho ranged from 0.61 to 0.94 for total and subscale scores. The interrater reliability at the item level of the FMMA showed (i) percentage agreement values with a median of 77% (range 44-100%), (ii) weighted Cohen's kappa coefficients with a median of 0.69 (range 0.00-0.98) and (iii) Gwet's AC1/AC2 coefficients with a median of 0.84 (range 0.42-0.98). Discussion and conclusion: The FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level.
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BACKGROUND: Patients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022. METHODS: This study is a secondary analysis of data from MAAESTRO with a matched nested case-control design and 1:2 ratio. DOAC intake was measured with a small electronic device (Time4MedTM). We defined two arbitrary intervals of 17 days and 95 days as the longest time spans with electronic monitoring data per patient to maximize the number of participants with adequate amount of observation time available for analysis. Taking and timing adherence were calculated retrospectively i.e., prior to the recurrent event for cases. Trendline analysis of adherence over 95 days was calculated. Linear regression analysis was performed after adjusting for the co-variables age and daily pill burden. Sensitivity analysis was performed with controls for intervals in the reverse direction (prospectively). RESULTS: We analyzed 11 cases and 22 matched controls (mean age: 75.9 ± 9.2 years vs. 73.1 ± 8.4 years; n.s.) with similar stroke characteristics (NIHSS, mRS, MoCA) and 36.4% women in each group. Mean adherence values were high and similar between cases and controls (95 days taking: 87.0 ± 18.9% (cases) vs. 90.8 ± 9.8% (controls), n.s.; similar values for timing adherence). Six hemorrhagic and five ischemic events had occurred. Compared to controls, a significantly higher 95 days taking adherence was observed for hemorrhagic events (96.0 ± 5.0% (cases) vs. 88.1 ± 11.5% (controls); p<0.01) and a significantly lower 95 days taking adherence was observed for ischemic events (75.7 ± 24.8% (cases) vs. 94.2 ± 6.2% (controls), p = 0.024). Values for timing adherence were similar. A non-significant downward linear trend of adherence was observed over 95 days independently of the clinical events. The sensitivity analysis showed that the direction of the interval had negligible impact on the 95 days adherence. CONCLUSION: Because recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC <76%, adherence enhancing interventions seem crucial in anticoagulated AF-patients. However, AF-patients with high adherence might benefit from a regular re-assessment of the bleeding risk as hemorrhagic complications were associated with adherence to DOAC >96%. TRIAL REGISTRATION: ClinicalTrials.gov NCT03344146.
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Anticoagulantes , Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Cumplimiento de la Medicación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración Oral , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Estudios de Casos y Controles , Hemorragia/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Estudios Retrospectivos , Prevención Secundaria/métodosRESUMEN
BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Cerebral/epidemiología , Infarto Cerebral/complicaciones , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hemorragias Intracraneales/complicaciones , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular Isquémico/complicaciones , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia/complicaciones , Estudios Prospectivos , Factores de Riesgo , Prevención Secundaria , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. METHODS: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months. RESULTS: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). CONCLUSIONS: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.
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Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.
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Disección de la Arteria Carótida Interna , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Disección de la Arteria Vertebral , Humanos , Adulto Joven , American Heart Association , Arterias , Disección de la Arteria Carótida Interna/diagnóstico , Disección de la Arteria Carótida Interna/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Disección de la Arteria Vertebral/diagnóstico , Disección de la Arteria Vertebral/diagnóstico por imagen , AdultoRESUMEN
BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.
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Disección Aórtica , Fibrilación Atrial , Disección de la Arteria Carótida Interna , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Estudios Retrospectivos , Disección de la Arteria Carótida Interna/complicaciones , Disección de la Arteria Carótida Interna/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Hemorragia/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Arterias , Fibrilación Atrial/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (>median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.
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Anticoagulantes , Aspirina , Disección de la Arteria Vertebral , Humanos , Femenino , Masculino , Persona de Mediana Edad , Disección de la Arteria Vertebral/tratamiento farmacológico , Disección de la Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/complicaciones , Aspirina/uso terapéutico , Anticoagulantes/uso terapéutico , Adulto , Fibrinolíticos/uso terapéutico , Anciano , Resultado del TratamientoRESUMEN
BACKGROUND: Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. AIM: The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. METHODS: We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. RESULTS: Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641). CONCLUSION: The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.
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Hemorragia Cerebral , Inhibidores del Factor Xa , Proteínas Recombinantes , Humanos , Hemorragia Cerebral/inducido químicamente , Masculino , Femenino , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Anciano , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Estudios Prospectivos , Factor Xa/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Hematoma , Tromboembolia/tratamiento farmacológicoRESUMEN
BACKGROUND: Direct oral anticoagulants (DOAC) effectively prevent recurrent ischaemic events in atrial fibrillation (AF) patients with recent stroke. However, excellent adherence to DOAC is mandatory to guarantee sufficient anticoagulation as the effect quickly subsides. AIM: To investigate the effect of intake reminders on adherence to DOAC. METHODS: MAAESTRO was a randomised, cross-over study in DOAC-treated AF patients hospitalised for ischaemic stroke. Adherence was measured by electronic monitoring for 12 months. After an observational phase, patients were randomised to obtain an intake reminder either in the first or the second half of the subsequent 6-month interventional phase. The primary outcome was 100%-timing adherence. Secondary outcomes were 100%-taking adherence, and overall timing and taking adherence. We analysed adherence outcomes using McNemar's test or mixed-effects logistic models. RESULTS: Between January 2018 and March 2022, 130 stroke patients were included, of whom 42 dropped out before randomisation. Analysis was performed with 84 patients (mean age: 76.5 years, 39.3% women). A 100%-timing adherence was observed in 10 patients who were using the reminder, and in zero patients without reminder (p = 0.002). The reminder significantly improved adherence to DOAC, with study participants having 2.7-fold increased odds to achieve an alternative threshold of 90%-timing adherence (OR 2.65; 95% CI 1.05-6.69; p = 0.039). A similar effect was observed for 90%-taking adherence (OR 3.06; 95% CI 1.20-7.80; p = 0.019). Overall timing and taking adherence increased significantly when using the reminder (OR 1.70; 95% CI 1.55-1.86, p < 0.01; and OR 1.67; 95% CI 1.52-1.84; p < 0.01). CONCLUSION: Intake reminders increased adherence to DOAC in patients with stroke attributable to atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03344146.
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Anticoagulantes , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Administración Oral , Anticoagulantes/uso terapéutico , Fibrilación Atrial/prevención & control , Isquemia Encefálica/prevención & control , Estudios Cruzados , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Background and aim: Loss of time is a major obstacle to efficient stroke treatment. Our telestroke path intends to optimize prehospital triage using a video link connecting ambulance personnel and a stroke physician. The objectives were as follows: (1) To identify patients suffering a stroke and (2) in particular large vessel occlusion (LVO) strokes as candidates for endovascular treatment. We have chosen the Rapid Arterial Occlusion Evaluation (RACE) scale for this purpose. Methods: This analysis aimed to verify the feasibility of prehospital stroke identification by video assessment. In this prospective telestroke cohort study, we included 97 subjects, in which the RACE score (items: facial palsy, arm and leg motor function, head and gaze deviation, and aphasia or agnosia) was applied, and the assessment videotaped by a trained member of the Emergency Medical Services (EMS) in the field using a mobile device. Each recorded patient video was independently assessed by three experienced stroke physicians from a certified stroke center and compared to the neuroimaging gold standard. Within this feasibility study, the stroke code was not altered by the outcome of the RACE assessment, and all patients underwent the standard procedures within the emergency unit. Results: We analyzed 97 patients (median age 78 years, 53% women), of whom 51 (52.6%) suffered an acute stroke, 12 (23.5%) of which were due to an LVO and 46 patients had symptoms mimicking a stroke. The sensitivity of stroke identification was 77.8%, and specificity was 53.6%. In regard to the identification of an LVO, sensitivity was 69.4% and specificity was 84.3%. The inter-rater agreement in the RACE-score assessment was ICC = 0.82 (intraclass-correlation coefficient). Conclusion: These results confirm our hypothesis that the local telestroke concept is feasible. It allows correct (i) stroke and (ii) LVO identification in the majority of the cases and thus has the potential to assist in efficient prehospital triage.
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BACKGROUND: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. OBJECTIVES: This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. METHODS: This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. RESULTS: Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for ß-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. CONCLUSIONS: These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under ß-blockers. This may inform secondary prevention strategies and trial design for CeAD.
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Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples. Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction. Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings). Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples.
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BACKGROUND: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. METHODS: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA. RESULTS: We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group. CONCLUSION: Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO.