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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., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rekk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. The Author(s).)

Objective: The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start., Methods: This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH., Results: A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke., Conclusions: Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start., Competing Interests: Competing interests: The following companies manufacture drugs involved in this study: Bayer (BY, rivaroxaban), Boehringer Ingelheim (BI, dabigatran), Pfizer/Bristol Meyer Squibb (PB, apixaban) and Daiichi Sankyo (DS, edoxaban). GMDM: scientific advisory boards and travel honoraria: BY; speaker honoraria: PB. DJS: scientific advisory boards: BY and PB. GT: scientific advisory boards: BY, DS and BI. MK: speaker honoraria from DS, BY and PB. KT: speaker honoraria from DS, BY, BI and PB. KM: speaker honoraria from BY, travel grant from PB. PL: scientific advisory boards: BY, DS and BI; funding for travel or speaker honoraria: BY and BI; research funding: BI. LHB: consultancy or advisory board fees or speaker’s honoraria from BY and PB. MP: honoraria as a member of the speaker bureau of BI, BY and PB. SE: funding for travel or speaker honoraria: BY, BI, PB and DS; scientific advisory boards: BY, BI and PB; educational grant from PB; research grant from DS. DJW: speaking honoraria: BY., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection., Methods: We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460., Findings: Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group., Interpretation: Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection., Funding: Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset., Methods: We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference., Results: We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I 2  = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I 2  = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I 2  = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I 2  = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I 2  = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH., Conclusion: This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.

Objective: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia., Methods: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs)., Results: We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09)., Interpretation: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Background: 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., Recent Developments: 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. WHERE NEXT?: 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Since their market approval, direct oral anticoagulants (DOACs) are being increasingly used for stroke prevention in patients with atrial fibrillation. However, the management of DOAC-treated patients with stroke poses several challenges for physicians in everyday clinical practice, both in the acute setting and in long-term care. This has spurred extensive research activity in the field over the past few years, which we review here.

Objective: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain., Methods: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension., Results: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm 3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43)., Interpretation: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712., (© 2018 American Neurological Association.)

Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH)., Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours., Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH ( p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [ p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [ p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [ p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [ p = 0.11])., Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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; DOAC early ) and those with late (>7 days, DOAC late ) 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 DOAC early (5.1%/y) and DOAC late (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., (© 2016 American Academy of Neurology.)

Background: Vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) are beneficial in patients with stroke and atrial fibrillation (AF). However, little is known about frequency and determinants of adherence to NOACs/VKAs in clinical practice., Methods: This is a single-center explorative study from the Novel Oral Anticoagulants in Stroke Patients (NOACISP)-LONGTERM registry. We included consecutive AF-stroke patients treated with NOACs/VKAs and followed up for 3-24 months. Adherence was assessed at follow-up using structured interviews and quantified as the proportion of prescribed doses taken (PDT). Outcome measures were (i) full adherence, (ii) ≥95% adherence and (iii) ≥80% adherence (i.e., PDT 100/≥95/≥80%). To explore determinants of full adherence, we compared characteristics of fully and non-fully adherent patients., Results: A total of 218 of 251 (86.9%) patients (48% female, mean age 77.9 ± 9.1 years, 78% NOACs; 22% VKAs) were eligible for analysis with a median follow-up of 12 months: fully adherent were 78.4% patients (NOACs 77.1%, VKAs 83.3%, p = 0.35), ≥95% adherent were 95.4% and ≥80% adherent were 97.2%. Fully adherent patients took more pills daily (median (interquartile range) 7 (5-10) vs. 6 (4-8), p = 0.039), had more often previous antithrombotic treatment (70.8 vs. 53.2%, p = 0.023), caregiver-assisted medication administration (54.2 vs. 19.1%, p < 0.001) and functional dependency (32.8 vs. 15%, p = 0.011) than non-fully adherent patients., Conclusions: Full adherence was frequent. Patients naïve to antithrombotics, taking few pills, which they self-administer, were at the highest risk of non-adherence and may benefit most from adherence-enhancing interventions., (© 2016 S. Karger AG, Basel.)

Background: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC)., Methods and Results: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences., Conclusions: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests., (© 2015 American Heart Association, Inc.)

Background and Purpose: To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment., Methods: This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant)., Results: Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed., Conclusion: New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials., (© 2015 EAN.)

Background and Purpose: The widespread preference of anticoagulants over antiplatelets in patients with cervical artery dissection (CAD) is empirical rather than evidence-based. Summary of Review- This article summarizes pathophysiological considerations, clinical experiences, and the findings of a systematic metaanalysis about antithrombotic agents in CAD patients. As a result, there are several putative arguments in favor as well as against immediate anticoagulation in CAD patients., Conclusions: A randomized controlled trial comparing antiplatelets with anticoagulation is needed and ethically justified. However, attributable to the large sample size which is required to gather meaningful results, such a trial represents a huge venture. This comprehensive overview may be helpful for the design and the promotion of such a trial. In addition, it could be used to encourage both participation of centers and randomization of CAD patients. Alternatively, antithrombotic treatment decisions can be customized based on clinical and paraclinical characteristics of individual CAD patients. Stroke severity with National Institutes of Health Stroke Scale score > or =15, accompanying intracranial dissection, local compression syndromes without ischemic events, or concomitant diseases with increased bleeding risk are features in which antiplatelets seem preferable. In turn, in CAD patients with (pseudo)occlusion of the dissected artery, high intensity transient signals in transcranial ultrasound studies despite (dual) antiplatelets, multiple ischemic events in the same circulation, or with free-floating thrombus immediate anticoagulation is favored.

Objective: To evaluate long-term outcome after extracranial internal carotid artery dissection (eICAD) in consideration of the applied antithrombotic therapy., Material and Methods: Among 33 consecutive eICAD patients initially treated either with anticoagulation (n = 25) or with antiplatelets (n = 8), a standardized interview was performed after 28 +/- 22.1 months to analyze risks and benefits of both agents. Ischemic and hemorrhagic complications, occurrence of seizure and rates of arterial recanalization were compared and long-term clinical outcome was assessed using the modified Rankin Scale (mRS) and Barthel Index (BI)., Results: Among anticoagulated patients, 1 died due to brain herniation. In 3 patients stroke (n = 2) or TIA (n = 1) recurred. In the antiplatelet group, none died and no subsequent ischemic events happened. Hemorrhagic complications were noted in neither treatment group. Functional outcome among anticoagulated patients was BI 92 +/- 21.6 and mRS 1.48 +/- 1.50, which did not differ from patients initially treated with antiplatelets (BI 89 +/- 18.9, mRS 1.50 +/- 1.41, p > 0.05). Four anticoagulated patients developed seizures, compared to 2 patients with antiplatelets (p > 0.05). Arterial recanalization occurred in 16 of 22 antico- agulated patients with ultrasound follow-up, compared to 6 of 6 patients with antiplatelets (p > 0.05)., Conclusion: In the absence of iatrogenic side effects, both anticoagulation and antiplatelets seem to be safe for eICAD. The rates for death and stroke were low and outcome ratings did not differ between both agents. These findings may indicate that a controlled randomized trial comparing anticoagulation and antiplatelets is ethically justified., (Copyright 2000 S. Karger AG, Basel)