Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on ...the daily help of others at hospital discharge are scarce.
Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders.
We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio HR, 0.58 95% CI, 0.42–0.81), as did independent compared to dependent patients (HR, 0.54 95% CI, 0.40–0.71). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HRdependent, 0.68 95% CI, 0.45–1.01) and independent patients (HRindependent, 0.44 95% CI, 0.26–0.75) in the simple model (Pinteraction=0.212). Adjusted (HRdependent, 0.74 95% CI, 0.49–1.11 and HRindependent, 0.51 95% CI, 0.30–0.87; Pinteraction=0.284) and weighted models (HRdependent, 0.79 95% CI, 0.48–1.31 and HRindependent, 0.46 95% CI, 0.26–0.81; Pinteraction=0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses.
The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03826927.
Objective
The objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults.
Methods
Embase and Medline ...literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
Results
A total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation SD 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% SD 38.6%), confusion (one study; 17.4%), local irritation (mean 16.6% SD 9.6%), and sedation (mean 12.7% SD 9.7%).
Conclusions
Administration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.
Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain.
We compared consecutive patients in the ...Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score
3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with
4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias.
One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio OR, 1.75 1.42-2.16;
<0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 1.08-2.36;
=0.020), and the propensity score matching analysis (n=568; OR, 1.61 1.20-2.15;
=0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 0.59-4.64), symptomatic intracranial hemorrhage (OR, 1.06 0.30-3.75), dependency or death (OR, 1.42 0.91-2.23), or mortality (OR, 1.65 0.94-2.89). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 1.76-5.04), dependency or death (OR, 1.49 1.07-2.07), and mortality (OR, 1.65 1.11-2.45) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 0.73-4.29).
This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.
Serum neurofilament light chain (sNfL) levels represent a promising marker of neuroaxonal injury. They are elevated in several neurological conditions, but their importance in cerebrovascular ...diseases remains unclear. In a proof of concept study, we compared sNfL levels with clinical characteristics and outcome in patients with cervical artery dissection (CeAD).
A total of 49 non-traumatic CeAD patients were included. sNfL levels were measured by high-sensitivity electrochemiluminescence immunoassay. Levels were compared with regard to (i) type of presenting symptoms (local symptoms only (n = 8), transient ischemic attack (TIA; n = 10) or ischemic stroke (n = 31)), (ii) stroke severity quantified by National Institute of Health Stroke Scale (NIHSS), (iii) time interval between onset of symptoms and blood sampling and (iv) 3-month outcome as measured by the modified Rankin Scale score. Analyses were performed using univariate and multivariate linear and ordinal regression models.
CeAD patients presenting with stroke had significantly higher sNfL levels (median 108.9 pg/ml, interquartile range (37.8-427.7)) than patients with TIA (16.4 pg/ml (8.7-36.3), p = 0.002) or local symptoms (23.4 pg/ml (17.8-30.8), p = 0.0007). Among stroke patients, sNfL levels were positively associated with both NIHSS (p = 0.0002) and time between stroke onset and serum sampling (p = 1.9 × 10-6). Higher sNfL levels were associated with unfavorable outcome at 3 months (OR 4.67, 95% CI 1.69-12.95, p = 0.003). However, this association lost significance after adjustment for NIHSS. The highest sNfL level was observed in a TIA patient who had ischemic stroke 1 day after serum sampling for sNfL measurement.
sNfL levels were increased in CeAD patients presenting with stroke, correlated with clinical severity and were influenced by the time point of blood sampling. The prognostic meaning of sNfL in CeAD deserves further testing.
Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the potential clinical usefulness is their ...rapid availability in emergency situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (NOACISP, cinicaltrials.gov:NCT02353585). We included consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban (last intake <48 h) in which RivLev determined by an automated anti-factor Xa-based chromogenic assay (Hyphen-Biomed, France) are available. Primary endpoint was the turnaround time (TAT), defined as time from registration of the blood sample in the lab to first result published. Furthermore, we studied, whether TAT is influenced by (1) on- and off-hour-measurements and (2) early versus later patient arrival (cut-off: 270 min after symptom onset). Thirty-eight patients met the eligibility criteria (mean age 77 years, 44 % female). TAT was 34 min (IQR 29–65 min). TATs were similar for on- (n = 14; median 34 min; IQR 30–56 min) and off-hours-TATs (n = 24; median 35 min; IQR 29–75 min) as well as for early (n = 16; median 33 min; IQR 30–40 min) and late patient arrival (n = 22, median 34 min, IQR 28–58 min; all nonsignificant.). Taking into account RivLev in the decision process about the use of intravenous thrombolysis, three patients received intravenous thrombolysis on an individualized basis, none of them with bleeding complications. Emergency measurement of RivLev among patients with acute stroke is available within a median of 34 min and therefore feasible for ED use. Due to the rapid availability, further research to evaluate the role of RivLev in order to guide acute treatment decisions is warranted.
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.
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.
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.
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.
Background:
Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce.
Methods:
We used prospectively obtained data from an observational registry ...(Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed.
Results:
Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR 95% CI 1.64 1.11, 2.40, p = 0.017) and recurrent IS (aHR 2.96 1.65, 5.35 , p < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause.
Conclusion:
In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients.
Clinical Trial Registration:
NCT 03826927
Graphical abstract
Introduction
Cerebral small vessel disease is an important cause for both ischaemic stroke and intracranial haemorrhage. To date, knowledge on the impact of small vessel disease on the clinical ...course in stroke patients treated with oral anticoagulation for atrial fibrillation is limited.
Patients and Methods
Registry-based prospective observational study of 320 patients (aged 78.2 ± 9.2 years) treated with anticoagulation following atrial fibrillation stroke. Patients underwent standardised magnetic-resonance-imaging assessing measures of small vessel disease, including cerebral microbleeds and white matter hyperintensities. Median follow-up was 754 (interquartile range = 708–828) days. Using adjusted logistic and Cox regression, we assessed the association of imaging measures with clinical outcome including recurrent ischaemic stroke, intracranial haemorrhage and death and assessed disability (modified Rankin Scale).
Results
Overall, recurrent ischaemic stroke was more common than intracranial haemorrhage (22 versus 8, respectively). Cerebral microbleeds were related to an increased risk of the composite endpoint (ischaemic stroke, intracranial haemorrhage, death: odds ratio (OR) 2.05, 95% confidence interval (CI) 1.27–3.31; P = 0.003), as were white matter hyperintensities (OR 2.00, 95%CI 1.23–3.27, P = 0.005). This was also true in time-to-event analysis (cerebral microbleeds: HR 2.31, 95%CI 1.39–3.52; P < 0.001; white matter hyperintensities: HR 1.99, 95%CI 1.20–3.17; P = 0.007). Both measures were associated with an increased risk for recurrent ischaemic stroke (cerebral microbleeds: HR 4.42, 95%CI 1.07–18.20; P = 0.04; white matter hyperintensities: HR 5.27, 95%CI 1.08–25.79, P = 0.04) and intracranial haemorrhage (cerebral microbleeds: HR 2.43, 95%CI 1.04–5.69; P = 0.04; white matter hyperintensities: HR 2.57, 95%CI 1.11–5.98, P = 0.03). Furthermore, confluent white matter hyperintensities were associated with increased disability (OR 4.03; 95%CI 2.16–7.52; P < 0.001) and mortality (HR 1.81, 95%CI 1.04–3.14, P = 0.04).
Discussion and conclusion
In atrial fibrillation stroke patients treated with oral anticoagulation, small vessel disease is associated with an unfavourable outcome. The presence of microbleeds indicated a risk higher for recurrent ischaemic stroke than for intracranial haemorrhage.
Background:
Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in ...patients with atrial fibrillation (AF) and recent stroke are scarce.
Patients and methods:
Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome – the composite of recurrent ischemic stroke, major bleeding, and all-cause death – among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders.
Results:
We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR 95% CI 0.69 0.48, 1.01 and 0.66 0.47, 0.91, respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR 95% CI 0.94 0.70, 1.26). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC.
Discussion and conclusion:
The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.
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