Summary Background Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised ...International Carotid Stenting Study comparison of these treatments. Methods Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat (ITT all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. Findings 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0–5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio HR 1·06, 95% CI 0·72–1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28–2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02–2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. Interpretation Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. Funding Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.
About 13–26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. Deciding when to initiate oral anticoagulation in patients ...with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Although the risk of early recurrent ischaemic stroke is high in this population, early oral anticoagulation is suspected to increase the risk of potentially harmful intracranial haemorrhage, including haemorrhagic transformation of the infarct. This assumption, and current treatment guidelines, are based on historical, mostly observational data from patients with ischaemic stroke and atrial fibrillation treated with heparins, heparinoids, or vitamin K antagonists (VKAs) to prevent recurrent ischaemic stroke. Randomised controlled trials have subsequently shown that direct oral anticoagulants (DOACs; ie, apixaban, dabigatran, edoxaban, and rivaroxaban) are at least as effective as VKAs in primary and secondary prevention of atrial fibrillation-related ischaemic stroke, with around half the risk of intracranial haemorrhage. However, none of these DOAC trials included patients who had experienced ischaemic stroke recently (within the first few weeks). Clinicians therefore remain uncertain regarding when to commence DOAC administration after acute ischaemic stroke in patients with atrial fibrillation.
Prospective observational studies and two small randomised trials have investigated the risks and benefits of early DOAC-administration initiation (most with a median delay of 3–5 days) in mild-to-moderate atrial fibrillation-associated ischaemic stroke. These studies reported that early DOAC treatment was associated with a low frequency of clinically symptomatic intracranial haemorrhage or surrogate haemorrhagic lesions on MRI scans, whereas later DOAC-administration initiation (ie, >7 days or >14 days after index stroke) was associated with an increased frequency of recurrent ischaemic stroke.
Adequately powered randomised controlled trials comparing early to later oral anticoagulation with DOACs in ischaemic stroke associated with atrial fibrillation are justified to confirm the acceptable safety and efficacy of this strategy. Four such randomised controlled trials (collectively planned to include around 9000 participants) are underway, either using single cutoff timepoints for early versus late DOAC-administration initiation, or selecting DOAC-administration timing according to the severity and imaging features of the ischaemic stroke. The results of these trials should help to establish the optimal timing to initiate DOAC administration after recent ischaemic stroke and whether the timing should differ according to stroke severity. Results of these trials are expected from 2021.
Dissection of Cervical and Cerebral Arteries Engelter, Stefan T.; Traenka, Christopher; Lyrer, Philippe
Current neurology and neuroscience reports,
08/2017, Letnik:
17, Številka:
8
Journal Article
Recenzirano
Purpose of Review
We aimed to summarize recent findings in cervical (CeAD) and intracranial artery dissection (IAD) research.
Recent Findings
Considered a disease of the young- and middle-aged, an ...analysis on the largest CeAD-population to date (
n
= 2391) revealed that about 1 of 14 CeAD-patients was aged ≥60 years. Distinct genetic variants were associated with CeAD. However, in clinical practice, genetic investigations are not helpful due to the small effect size. Despite the paucity of data from randomized-controlled trials in CeAD-stroke patients, both intravenous thrombolysis and endovascular treatment should be considered as acute treatment in such patients. Future research is needed to clarify which patients benefit most from each treatment modality. Whether to use antiplatelets or anticoagulants in stroke prevention in CeAD-patients is still a matter of debate. One randomized-controlled feasibility trial has been published, and another trial designed to show non-inferiority of aspirin to vitamin-K-antagonists is underway and will be terminated in late 2018. Non-vitamin-K-oral anticoagulants should not be used in CeAD outside a properly designed trial, as experience with these drugs in CeAD-patients is limited. With many IAD patients developing intracranial hemorrhage, antithrombotic therapy should be used with caution.
Summary
Knowledge about CeAD and IAD has advanced substantially. Nevertheless, further research is mandatory, in particular regarding pathophysiology, acute treatment, and stroke-preventive therapy, as well as long-term outcome and prognosis.
It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary ...prevention should be managed.
We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists VKA or direct oral anticoagulants DOAC) prior to index event (OAC
) with those without prior oral anticoagulation (OAC
). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC
) with those who continued the same anticoagulation as secondary prevention (OAC
). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
We included 5,413 patients (median age = 78 years interquartile range (IQR) = 71-84 years; 5,136 96.7% had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 IQR = 2-12). The median CHA
DS
-Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC
(n = 1,195) and OAC
(n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC
was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC
(n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC
(n = 585).
Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA
DS
-Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
OBJECTIVE:In patients with recent acute ischemic stroke (AIS) and atrial fibrillation, we assessed the starting time of direct, non–vitamin K antagonist oral anticoagulants (DOACs) for secondary ...prevention, the rate of intracranial hemorrhage (ICH), and recurrent ischemic events during follow-up.
METHODS:We included consecutive patients with nonvalvular atrial fibrillation admitted to our hospital for AIS or TIA (index event) who received secondary prophylaxis with DOAC or vitamin K antagonists (VKAs). Follow-up was at least 3 months. In the primary analysis, we compared rates of ICH and recurrent ischemic events (AIS or TIA) between patients with early (≤7 days since event; DOACearly) and those with late (>7 days, DOAClate) start of DOAC.
RESULTS:Two hundred four patients were included (median age 79 years, 89% AIS) and total follow-up time was 78.25 patient-years. One hundred fifty-five patients received DOAC with a median delay of 5 days after the index event (interquartile range 3–11) and 49 received VKA. DOAC was started early in 100 patients (65%). We observed one ICH (1.3%/y) and 6 recurrent AIS (7.7%/y). The ICH occurred in a patient taking VKA. No significant difference in the rate of recurrent AIS between DOACearly (5.1%/y) and DOAClate (9.3%/y, p = 0.53) was observed.
CONCLUSIONS:Even if DOACs are often started early after an index event, the risk of ICH appears to be low. Among all patients receiving anticoagulation, the rate of recurrent events was 6 times higher than the rate of ICH.
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.
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).
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.
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%.
ClinicalTrials.gov NCT03344146.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Extracranial internal carotid artery dissection (eICAD) is a leading cause of stroke in younger patients.
Objectives
1. To determine whether, in patients with eICAD, treatment with ...anticoagulants, antiplatelet agents or control was associated with a better functional outcome.
2. To compare, among patients treated with either anticoagulants or antiplatelet agents, the risk of ischaemic strokes and major bleeding episodes.
Search methods
We searched the Cochrane Stroke Group Trials Register (last searched 3 October 2009). In addition, we performed comprehensive searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (January 1966 to November 2009) and EMBASE (January 1980 to November 2009), checked all relevant papers for additional eligible studies and contacted authors and researchers in the field.
Selection criteria
Randomised controlled trials, controlled clinical trials and non‐randomised studies (if they reported on outcome stratified by antithrombotic treatment and included at least four patients) of anticoagulants or antiplatelet agents for the treatment of extracranial internal carotid artery dissection. Two review authors independently extracted data.
Data collection and analysis
Primary outcomes were death (all causes) and death or disability. Secondary outcomes were ischaemic stroke, symptomatic intracranial haemorrhage, and major extracranial haemorrhage during the reported follow‐up period. The first choice treatment was taken for analyses.
Main results
We did not find any completed randomised trials. Comparing antiplatelets with anticoagulants across 36 observational studies (1285 patients), there were no significant differences in the odds of death (Peto odds ratio (Peto OR) 2.02, 95% CI 0.62 to 6.60), or the occurrence of ischaemic stroke (OR 0.63, 95% CI 0.21 to 1.86) (34 studies, 1262 patients). For the outcome of death or disability, there was a non‐significant trend in favour of anticoagulants (OR 1.77, 95% CI 0.98 to 3.22; P = 0.06) (26 studies, 463 patients). Symptomatic intracranial haemorrhages (5/627; 0.8%) and major extracranial haemorrhages (7/425; 1.6%) occurred only in the anticoagulation group; however, for both these outcomes, the estimates were imprecise and indicated no significant difference between the two treatment modalities.
Authors' conclusions
There were no randomised trials comparing either anticoagulants or antiplatelet drugs with control, thus there is no evidence to support their routine use for the treatment of extracranial internal carotid artery dissection. There were also no randomised trials that directly compared anticoagulants with antiplatelet drugs and the reported non‐randomised studies did not show any evidence of a significant difference between the two.
The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial.
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.
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.
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 β-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.
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 β-blockers. This may inform secondary prevention strategies and trial design for CeAD.
Display omitted
The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ...ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment.
In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation.
MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
