Objective: elderly stroke patients were excluded or underrepresented in the randomised controlled trials of intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) applied ...within 3 h. Cohort studies comparing intravenous rtPA in stroke patients of ≥80 versus <80 years of age were limited by small sample sizes and yielded conflicting results. Thus, we performed a systematic review across all such studies. Methods: a systematic literature search (PubMed; Science Citation Index) was performed to retrieve all eligible studies. Two reviewers independently extracted data on ‘death’, ‘favourable 3-month outcome (modified Rankin Scale ≤1)’ and ‘symptomatic intracranial haemorrhage (sICH)’. Across studies, weighted odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated. Results: six studies were included n = 2,244 patients; 477 (21%) aged ≥80 years. Significant differences in baseline characteristics to the disadvantage of older patients were present in all studies. Compared with younger patients, older patients had a 3.09-time (95% CI = 2.37–4.03; P < 0.001) higher 3-month mortality and were less likely to regain a ‘favourable outcome’ (OR = 0.53; 95% CI = 0.42–0.66; P<0.001). The likelihood for ‘sICH’ (OR = 1.22; 95% CI = 0.77–1.94; P = 0.34) was similar in both age groups. Conclusion: intravenous rtPA-treated stroke patients of ≥80 years of age have a less favourable outcome than younger ones. Imbalances in predictive baseline variables to the disadvantage of the older patients may contribute to this finding. Compared with the younger cohort, rtPA-treated stroke patients aged ≥80 years do not seem exceedingly prone to sICH. Thus, there is scope for benefit from thrombolysis for the older age group. Hence, to obtain reliable evidence on the balance of risk and benefit of intravenous rtPA for stroke patients aged ≥80 years, it is safe and reasonable to include such patients in randomised placebo-controlled trials.
Intravenous thrombolysis is an approved treatment for anterior (ACS) and posterior (PCS) circulation stroke. However, no randomized controlled trial has investigated safety and efficacy of ...intravenous thrombolysis according to stroke territory, although PCS is assumed to differ from ACS in many ways. We aimed to compare the safety and clinical outcome of intravenous thrombolysis applied to patients with PCS and ACS.
Prospectively collected data of 883 consecutive patients with acute ischemic stroke (788 ACS, 95 PCS) treated with intravenous thrombolysis in 3 Swiss stroke centers were analyzed. Presenting characteristics, symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin scale 0 or 1) at 3 months were compared between patients with PCS and ACS.
As compared with patients with ACS, those with PCS were younger (mean age, 63 versus 67 years, P=0.012) and had a lower mean baseline National Institutes of Health Stroke Scale score (9 versus 12, P<0.001). Patients with PCS less often had symptomatic intracranial hemorrhage (0% versus 5%, P=0.026) and had more often a favorable outcome (66% versus 47%, P<0.001). Mortality was similar in the 2 groups (PCS, 9%; ACS, 13%; P=0.243). After multivariable adjustment, PCS was an independent predictor of lower symptomatic intracranial hemorrhage frequency (P=0.001), whereas stroke territory was not associated either with favorable outcome (P=0.177) or with mortality (P=0.251).
Our study suggests that PCS is associated with a lower risk of symptomatic intracranial hemorrhage after intravenous thrombolysis as compared with ACS, whereas favorable outcome and mortality were similar in the 2 stroke territories.
Summary Background Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions ...affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. Methods Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com , number ISRCTN 25337470. Findings 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17–6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10–8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40–3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38–5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29–6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45–27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. Interpretation The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. Funding Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.
Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it ...is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk.
Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation.
Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death.
Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54.
To derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS).
The derivation cohort consisted of patients with ...AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6.
Overall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval CI 0.787-0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72-78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32-60).
The biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin.
NCT00390962 (derivation cohort) and NCT00878813 (validation cohort).
To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).
We analysed consecutive patients with AF with ...an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.
Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.
Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.
ISRCTN48292829.
Serum neurofilament light chain (sNfL) is increasingly used as a neuroaxonal injury biomarker in the elderly. Besides age, little is known about how other physiological factors like renal function ...and body mass index (BMI) alter its levels. Here, we investigated the association of estimated glomerular filtration rate (eGFR) and BMI with sNfL in a large sample of elderly patients with atrial fibrillation (AF).
This is a cross-sectional analysis from the Swiss-AF Cohort (NCT02105844). We measured sNfL using an ultrasensitive single-molecule array assay. We calculated eGFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine (eGFR
) and creatinine-cystatin C (eGFR
) formulas, and BMI from weight and height measurements. We evaluated the role of eGFR and BMI as determinants of sNfL levels using multivariable linear regression and the adjusted R
(R
).
Among 2,277 Swiss-AF participants (mean age 73.3 years), eGFR
showed an inverse curvilinear association with sNfL after adjustment for age and cardiovascular comorbidities. BMI also showed an independent, inverse linear association with sNfL. The R
of models with age, eGFR
, and BMI alone was 0.26, 0.35, and 0.02, respectively. A model with age and eGFR
combined explained 45% of the sNfL variance. Sensitivity analyses (i) further adjusting for vascular brain lesions (
= 1,402 participants with MRI) and (ii) using eGFR
yielded consistent results.
In an elderly AF cohort, both renal function and BMI were associated with sNfL, but only renal function explained a substantial proportion of the sNfL variance. This should be taken into account when using sNfL in elderly patients or patients with cardiovascular disease.
To examine the import of prior cervical trauma (PCT) in patients with cervical artery dissection (CeAD).
In this observational study, the presence of and the type of PCT were systematically ...ascertained in CeAD patients using 2 different populations for comparisons: 1) age- and sex-matched patients with ischemic stroke attributable to a cause other than CeAD (non-CeAD-IS), and 2) healthy subjects participating in the Cervical Artery Dissection and Ischemic Stroke Patients Study. The presence of PCT within 1 month was assessed using a standardized questionnaire. Crude odds ratios (ORs) with 95% confidence intervals (CIs) and ORs adjusted for age, sex, and center were calculated.
We analyzed 1,897 participants (n = 966 with CeAD, n = 651 with non-CeAD-IS, n = 280 healthy subjects). CeAD patients had PCT in 40.5% (38.2%-44.5%) of cases, with 88% (344 of 392) classified as mild. PCT was more common in CeAD patients than in non-CeAD-IS patients (ORcrude 5.6 95% CI 4.20-7.37, p < 0.001; ORadjusted 7.6 95% CI 5.60-10.20, p < 0.001) or healthy subjects (ORcrude 2.8 95% CI 2.03-3.68, p < 0.001; ORadjusted 3.7 95% CI 2.40-5.56, p < 0.001). CeAD patients with PCT were younger and presented more often with neck pain and less often with stroke than CeAD patients without PCT. PCT was not associated with functional 3-month outcome after adjustment for age, sex, and stroke severity.
PCT seems to be an important environmental determinant of CeAD, but was not an independent outcome predictor. Because of the characteristics of most PCTs, the term mechanical trigger event rather than trauma may be more appropriate.
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.
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.
Background
The negative impact of the COVID-19 outbreak on stroke care has been reported, but no data exist on the influence of the lockdown on medication adherence to antithrombotic treatment for ...stroke prevention. We present a comparison of electronic adherence data of stroke patients treated with direct oral anticoagulants (DOAC) prior to and during the COVID-19 lockdown in spring 2020 in Switzerland.
Methods
This is a secondary analysis using data from the ongoing MAAESTRO study, in which stroke patients with atrial fibrillation electronically monitor their adherence to DOAC treatment. Eligible patients for this analysis had at least four weeks of adherence data prior to and during the COVID-19 lockdown. Three adherence metrics (
taking adherence, timing adherence, drug holidays
) were calculated and compared descriptively.
Results
The analysis included eight patients (median age 81.5 years, IQR 74.8–84.5). Five patients had a pre-lockdown
taking adherence
over 90% (mean 96.8% ± 2.9), with no change during lockdown, high
timing adherence
in both periods and no
drug holidays
. The remaining three patients had pre-lockdown
taking
and
timing adherence
below 90%. Of those, two patients showed a moderate decline either in
taking
or
timing adherence
compared to pre-lockdown. One showed a substantial increase in
taking
and
timing adherence
during lockdown (both + 25.8%).
Conclusion
Our data suggest that a major disruption of social life (i.e., the imposed COVID-19 lockdown) is unlikely to relevantly affect the medication intake behaviour of patients with high pre-established adherence, but might have an impact in patients with previously suboptimal adherence.
Trial registration number
MAAESTRO: electronic Monitoring and improvement of Adherence to direct oral Anticoagulant treatment—a randomized crossover study of an Educational and reminder-based intervention in ischaemic STROke patients under polypharmacy, NCT03344146.
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