Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Long-Term Incidence of Ischemic Stroke After Transient Ischemic Attack: A Nationwide Study From 2014 to 2020.

BACKGROUND: The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies. METHODS: Patients with first-time TIA (index date) in the Danish Stroke Registry (January 2014-December 2020) were included and matched 1:4 with individuals from the background population and 1:1 with patients with a first-time ischemic stroke on the basis of age, sex, and calendar year. The incidences of ischemic stroke and mortality from index date were estimated by Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups using multivariable Cox regression. RESULTS: We included 21 500 patients with TIA, 86 000 patients from the background population, and 21 500 patients with ischemic stroke (median age, 70.8 years [25th-75th percentile, 60.8-78.7]; 53.1% males). Patients with TIA had more comorbidities than the background population, yet less than the control stroke population. The 5-year incidence of ischemic stroke after TIA (6.1% [95% CI, 5.7-6.5]) was higher than the background population (1.5% [95% CI, 1.4-1.6], P<0.01; hazard ratio, 5.14 [95% CI, 4.65-5.69]) but lower than the control stroke population (8.9% [95% CI, 8.4-9.4], P<0.01; hazard ratio, 0.58 [95% CI, 0.53-0.64]). The 5-year mortality for patients with TIA (18.6% [95% CI, 17.9-19.3]) was higher than the background population (14.8% [95% CI, 14.5-15.1], P<0.01; hazard ratio, 1.26 [95% CI, 1.20-1.32]) but lower than the control stroke population (30.1% [95% CI, 29.3-30.9], P<0.01; hazard ratio, 0.41 [95% CI, 0.39-0.44]). CONCLUSIONS: Patients with first-time TIA had an ischemic stroke incidence of 6.1% during the 5-year follow-up period. After adjustment for relevant comorbidities, this incidence was approximately 5-fold higher than what was found for controls in the background population and 40% lower than for patients with recurrent ischemic stroke.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Recognition of visual symptoms in stroke: a challenge to patients, bystanders, and Emergency Medical Services.

BACKGROUND: Identification of visual symptoms as a sign of acute stroke can be challenging for both first line healthcare professionals and lay persons. Failed recognition of visual symptoms by medical dispatchers at the Emergency Medical Dispatch Center (EMDC-112) or personnel at the Out-of-Hours Health Service (OOHS) may delay stroke revascularization. We aimed to identify correct system response to visual symptoms in emergency calls. METHODS: Phone calls from patient or bystander to the EMDC-112 or OOHS, which included visual symptoms on patients later verified with stroke/Transient ischemic attack (TIA) diagnosis, were analyzed. Data were stratified according to hospitalization within and after 4.5 h from symptom onset. Descriptive and multiple logistic regression analysis were performed. RESULTS: Of 517 calls identified, 290 calls fulfilled inclusion criteria. Only 30% of the patients received correct visitation by the medical dispatchers and referral to the hospital by a high-priority ambulance. Correct visitation was associated with early contact (adjusted OR: 2.37, 95% CI: 1.11, 5.03), contact to the EMDC-112 (adjusted OR: 3.18, 95% CI: 1.80, 5.62), and when the medical dispatcher asked additional questions on typical stroke symptoms (adjusted OR: 6.36, 95% CI: 3.01, 13.43). No specific visual symptom was associated with stroke recognition and fast hospitalization. CONCLUSIONS: First line healthcare professionals had significant problems in identifying visual symptoms as a sign of acute stroke and eliciting correct response. This highlights an urgent need to improve knowledge of visual symptoms in acute stroke and emphasize correct response to stroke symptoms in general.

High-intensity training in patients with lacunar stroke: A one-year follow-up.

OBJECTIVES: Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke. MATERIALS AND METHODS: Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke. RESULTS: We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group. CONCLUSIONS: Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.

The headache and aura-inducing effects of sildenafil in patients with migraine with aura.

INTRODUCTION: It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura. METHODS: In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura. RESULTS: Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher's exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher's exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks. DISCUSSION: Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase.Trial registration: ClinicalTrials.gov - NCT02795351.

COVID-19 did not result in increased hospitalization for stroke and transient ischemic attack: A nationwide study.

BACKGROUND: The risk of thrombosis increases in infectious diseases, yet observational studies from single centers have shown a decrease in admission of acute ischemic stroke patients during the COVID-19 pandemic. To investigate unselected stroke admission rates we performed a nationwide study in Denmark. METHODS: We extracted information from Danish national health registries. The following mutually exclusive time periods were compared to the year before the lockdown: (1) first national lockdown, (2) gradual reopening, (3) few restrictions, (4) regional lockdown, and (5) second national lockdown. RESULTS: Generally, admission rates were unchanged during the pandemic. In the unadjusted data, we observed a small decrease in the admission rate for all strokes under the first lockdown (incidence rate ratio: 0.93, confidence interval [CI]: 0.87-0.99) and a slight increase during the periods with gradual reopening, few restrictions, and the regional lockdown driven by ischemic strokes. We found no change in the rate of severe strokes, mild strokes, or 30-day mortality. An exception was the higher mortality for all strokes during the first lockdown (risk ratio: crude 1.30 [CI: 1.03-1.59]; adjusted 1.17 [CI: 0.93-1.47]). The quality of care remained unchanged. CONCLUSION: Stroke admission rates remained largely unchanged during the pandemic, while an increased short-term mortality rate in patients admitted with stroke observed during the first lockdown was seen, probably reflecting that the more frail patients constituted a higher proportion of admitted patients at the beginning of the pandemic.

Stroke admissions and revascularization treatments in Denmark during COVID-19.

OBJECTIVE: The aim of this study was to assess the number of stroke-related admissions and acute treatments during the first two waves of COVID-19 and lockdowns in the Capital Region of Denmark and the Region of Zealand. MATERIALS & METHODS: The weekly numbers of admitted patients with stroke were retrieved from electronic patient records from January 2019 to February 2021 and analysed to reveal potential fluctuations in patient volumes during the pandemic. RESULTS: A total of 23,688 patients were included, of whom 2049 patients were treated with tissue-type plasminogen activators (tPA) and 552 underwent endovascular thrombectomy (EVT). We found a transient decrease in the number of weekly admitted patients (pts/week) with all strokes (-9.8 pts/week, 95% CI: -19.4; -0.2, p = .046) and stroke mimics (-30.1 pts/week, 95% CI: -39.9; -20.3, p < .001) during the first lockdown compared to pre-COVID-19. The number of subarachnoid haemorrhage, intracerebral haemorrhage, and ischaemic stroke admissions showed insignificant declines. Analysing all COVID-19 periods collectively revealed increased volumes of ischaemic stroke (+6.2 pts/week, 95% CI: +1.6; +10.7, p = .009) compared to pre-COVID levels, while numbers of stroke mimics remained lower than pre-COVID. Weekly tPA and EVT treatments remained constant throughout the study period. CONCLUSIONS: Our results are comparable with other studies in finding reductions in stroke-related admissions early in the pandemic. This is the first study to report increased stroke volumes following the first wave of the pandemic. The mechanisms behind the observed drop and subsequent rise in strokes are unclear and warrant further investigation.

Incidence of ischaemic stroke and mortality in patients with acute coronary syndrome and first-time detected atrial fibrillation: a nationwide study.

AIMS: The aim of this study was to examine contemporary data on the 1-year prognosis of patients surviving acute coronary syndrome (ACS) and concomitant first-time detected atrial fibrillation (AF). METHODS AND RESULTS: Using Danish nationwide registries, we identified all patients surviving a first-time admission with ACS from 2000 to 2018 and grouped them into (i) those without AF prior to or during ACS; (ii) those with a history of AF; and (iii) those with first-time detected AF during admission with ACS. With 1 year of follow-up, rates of ischaemic stroke, death, and bleeding were compared between study groups using multivariable adjusted Cox proportional hazards analysis. We included 161 266 ACS survivors: 135 878 (84.2%) without AF, 18 961 (11.8%) with history of AF, and 6427 (4.0%) with first-time detected AF at admission with ACS. Compared to those without AF, the adjusted 1-year rates of outcomes were as follows: ischaemic stroke [hazard ratio (HR) 1.38 (95% CI 1.22-1.56) for patients with history of AF and HR 1.67 (95% CI 1.38-2.01) for patients with first-time detected AF]; mortality [HR 1.25 (95% CI 1.21-1.31) for patients with history of AF and HR 1.52 (95% CI 1.43-1.62) for patients with first-time detected AF]; and bleeding [HR 1.22 (95% CI 1.14-1.30) for patients with history of AF and HR 1.28 (95% CI 1.15-1.43) for patients with first-time detected AF]. CONCLUSION: In patients with ACS, first-time detected AF appeared to be at least as strongly associated with the 1-year rates of ischaemic stroke, mortality, and bleeding as compared with patients with a history of AF.

The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment.

INTRODUCTION: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. METHODS: In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. RESULTS: Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (-7.8, -4.9 mmHg; P < .001). No serious adverse events were observed. DISCUSSION: This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Time to Thrombolysis and Long-Term Outcomes in Patients With Acute Ischemic Stroke: A Nationwide Study.

Background and Purpose: It is well-established that increasing treatment delay reduces the benefits of thrombolysis in patients with acute ischemic stroke. However, most studies focus on short-term outcomes. This study examined long-term outcomes according to time to thrombolysis in patients with first-time ischemic stroke. Methods: In this nationwide cohort study, all Danish patients with first-time ischemic stroke treated with intravenous thrombolysis between 2011 and 2017 and alive at discharge were identified through the Danish Stroke Registry. The association between time from symptom onset to thrombolysis and the long-term rate of the composite of death and recurrent ischemic stroke was examined using multivariable Cox regression and restricted cubic spline analysis. Results: The study population included 6252 patients with first-time ischemic stroke treated with thrombolysis (median age, 69 years [25th­75th percentile 60­78 years], 60% men). The median follow-up was 2.5 years (25th­75th percentile 1.2­4.1 years). The median time to thrombolysis was 138 minutes (25th­75th percentile 101­185 minutes), and the median National Institutes of Health Stroke Scale score at presentation was 5 (25th­75th percentile 3­10). The absolute 3-year risk of the composite outcome was 19.0% (95% CI, 16.4%­21.8%) in the 0 to 90 minute group, 23.3% (21.8%­24.9%) in the 91 to 180 minute group, and 23.8% (21.6%­26.1%) in the 181 to 270 minute group. Compared with thrombolysis within 90 minutes, time to thrombolysis >90 minutes was associated with a higher rate of the composite outcome (91­180 minute: adjusted hazard ratio, 1.25 [95% CI, 1.06­1.48]; 181­270 minutes: adjusted hazard ratio, 1.35 [95% CI, 1.12­1.61]). In restricted cubic spline analysis, the rate of the composite outcome increased with increasing time to thrombolysis and leveled off after 138 minutes. Conclusions: In this nationwide cohort of patients with ischemic stroke, the long-term rate of the composite of death and recurrent ischemic stroke increased with increasing time from symptom onset to initiation of thrombolysis.

Recurrent Ischemic Stroke - A Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time. METHODS AND MATERIALS: A systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019. RESULTS: The search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence. CONCLUSION: Stroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.

Nursing Home Admission and Initiation of Domiciliary Care After Ischemic Stroke - The Importance of Time to Thrombolysis.

OBJECTIVES: There is a paucity of data on the risk of nursing home admission or domiciliary care initiation according to time to intravenous thrombolysis for ischemic stroke. We investigated the association between time to intravenous thrombolysis and the composite of nursing home admission or domiciliary care initiation in patients with acute ischemic stroke. MATERIALS AND METHODS: In this nationwide cohort study, all stroke patients treated with intravenous thrombolysis (2011-2015) and alive at discharge were identified from the Danish Stroke Registry and other nationwide registries. The composite of nursing home admission or domiciliary care initiation one year post-discharge according to time to thrombolysis was examined with multivariable Cox regression. RESULTS: The study population comprised 4,349 patients (median age 67 years [25th-75th percentile 57-75], 65.2% men). The median National Institutes of Health Stroke Scale score at presentation was 5, and the median time from symptom-onset to initiation of thrombolysis was 143 min. The absolute 1-year risk of the composite endpoint was 14.0% (95%CI, 11.5-16.8%) in the ≤90 min group, 16.6% (15.1-18.1%) in the 91-180min group, and 16.0% (14.0-18.2%) in the 181-270 min group. Compared with thrombolysis ≤90 min, time to thrombolysis between 91-180 min and 181-270 min was associated with a significantly higher risk of the composite endpoint (hazard ratio 1.31 [1.04-1.65] and 1.47 [1.14-1.91], respectively). CONCLUSIONS: In patients admitted with ischemic stroke, increasing time to thrombolysis was associated with a greater risk of the composite of nursing home admission or domiciliary care initiation. Continued efforts to shorten the time delay from symptom-onset to initiation of thrombolysis are warranted.

Workforce Attachment after Ischemic Stroke - The Importance of Time to Thrombolytic Therapy.

OBJECTIVES: The ability to remain in employment addresses an important consequence of stroke beyond the usual clinical parameters. However, data on the association between time to intravenous thrombolysis and workforce attachment in patients with acute ischemic stroke are sparse. MATERIALS AND METHODS: In this nationwide cohort study, stroke patients of working age (18-60 years) treated with thrombolysis (2011-2016) who were part of the workforce prior to admission and alive at discharge were identified using the Danish Stroke Registry. The association between time to thrombolysis and workforce attachment one year later was examined with multivariable logistic regression. RESULTS: The study population comprised 1,329 patients (median age 51 years [25th-75th percentile 45-56], 67.3% men). The median National Institutes of Health Stroke Scale score at presentation was 4 (25th-75th percentile 2-8), and the median time from symptom-onset to initiation of thrombolysis was 140min (25th-75th percentile 104-196min). The proportion of patients who were part of the workforce at one-year follow-up was 64.6%, 64.3%, 64.9%, and 60.0% in patients receiving thrombolysis within 90min, between 91-180min, between 181-270min, and after 270min, respectively. In adjusted analysis, time to thrombolysis between 91-180min, 181-270min, and >270min was not significantly associated with workforce attachment compared with thrombolysis received ≤90min of symptom-onset (ORs 0.89 [95%CI 0.60-1.31], 0.93 [0.66-1.31], and 0.80 [0.43-1.52], respectively). CONCLUSIONS: In patients of working age admitted with stroke and treated with thrombolysis, two out of three were part of the workforce one year after discharge. There was no graded relationship between time to thrombolysis and the likelihood of workforce attachment.

Beneficial impact of intensified multifactorial intervention on risk of stroke: outcome of 21 years of follow-up in the randomised Steno-2 Study.

AIMS/HYPOTHESIS: Epidemiological studies have shown that diabetes is a well-established independent but modifiable risk factor for stroke. The aim of this post hoc analysis of data from the Steno-2 Study was to examine whether multiple risk factor intervention reduced the risk for stroke in individuals with type 2 diabetes and microalbuminuria. METHODS: In the Steno-2 Study, 160 individuals with type 2 diabetes and microalbuminuria were randomised to intensified or conventional multiple risk factor intervention, targeting classical cardiovascular disease risk factors for a mean of 7.8 years, and then followed for a total mean of 21.2 years. The primary endpoint in this post hoc analysis was time to first stroke event. RESULTS: During follow-up, 30 participants experienced a total of 39 strokes. Individuals randomised to conventional therapy were more likely to experience a stroke than those in the intensive-therapy group, with 29 total strokes occurring in 21 participants (26%) in the conventional-therapy group vs a total of ten strokes in nine participants (11%) in the intensive-therapy group (HR 0.31 [95% CI 0.14, 0.69]; p = 0.004). Also, the number of recurrent strokes was significantly reduced with intensive therapy. CONCLUSIONS/INTERPRETATION: Intensified multiple risk factor intervention in patients with type 2 diabetes and microalbuminuria reduces the risk for strokes as well as the number of recurrent cerebrovascular events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00320008.

Induction of migraine-like headache, but not aura, by cilostazol in patients with migraine with aura.

Whether migraine headache and migraine aura share common pathophysiological mechanisms remains to be understood. Cilostazol causes cAMP accumulation and provokes migraine-like headache in migraine patients without aura. We investigated if cilostazol induces aura and migraine-like headache in patients with migraine with aura and alters peripheral endothelial function and levels of endothelial markers. In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 12 patients exclusively had attacks of migraine with aura) received 200 mg cilostazol (Pletal®) or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. Peripheral endothelial function was assessed by digital pulse amplitude tonometry using EndoPAT2000, and endothelial markers (VCAM1, E-selectin, and VEGFA) were measured. After administration of cilostazol, 14 patients (88%) experienced headache compared with six patients (38%) after placebo (P = 0.009). The headache in 12 patients (75%) after cilostazol and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (P = 0.0002). Patients reported that the attack mimicked the headache phase during their usual migraine attacks. However, aura symptoms were elicited in one patient after cilostazol and one patient after placebo. Further, endothelial function, as assessed by peripheral arterial tonometry, and endothelial markers were not significantly altered by cilostazol. Accumulation of cAMP by cilostazol induces migraine-like headache, but not aura, in patients with migraine with aura, even in those who exclusively reported attacks of migraine with aura in their spontaneous attacks. These findings further support dissociation between the aura and the headache phase with a yet unknown trigger for the aura and link between aura and headache. In addition, cilostazol administration did not significantly alter endothelial function, as assessed by peripheral arterial tonometry, or the endothelial markers, VCAM1, E-selectin, and VEGFA. However, post hoc analyses showed that our study was statistically underpowered for these outcomes.

Self-Reported Physical Activity and Cardiovascular Disease Risk Factors in Patients with Lacunar Stroke.

BACKGROUND: Physical inactivity is a major modifiable risk factor for stroke. The aim was to explore if stroke patients admitted with lacunar stroke adhere to the international recommendations on physical activity prestroke (≥150 minutes of moderate-intensity activity, or ≥75 minutes of vigorous-intensity activity, or an equivalent combination). Further, to assess association between prestroke physical activity and cardiovascular disease (CVD) risk factors. METHODS: A cross-sectional study, including patients with lacunar stroke according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Data collected included prestroke physical activity using the self-reported Physical Activity Scale. Cardiorespiratory fitness was estimated as the power output from the Graded Cycling Test with Talk Test and sociodemographic factors including age, sex, education, and CVD risk factors including pre-existing diabetes, history of hypertension, body mass index, and lipids were assessed. RESULTS: We included 19 women and 52 men (mean age 64 years). Overall, 79% of the recruited patients adhered to the physical activity recommendations prestroke, but only 35% did vigorous-intensity activity. Prestroke physical activity was associated with a history of hypertension. CONCLUSIONS: A high proportion of the lacunar stroke patients reported to adhere to the recommendations on physical activity prestroke; however, only one third engaged in vigorous-intensity activity. Studies are warranted to investigate if vigorous-intensity activity is effective as secondary prevention in patients with a lacunar stroke.

Does the Primary Imaging Modality-Computed Tomography or Magnetic Resonance Imaging-Influence Stroke Physicians' Certainty on Whether or Not to Give Thrombolysis to Randomized Acute Stroke Patients?

BACKGROUND: Door-to-needle time of 20 minutes to stroke patients with intravenous tissue plasminogen activator (iv-tPA) is feasible when computed tomography (CT) is used as first-line of brain imaging. Magnetic resonance imaging (MRI)-based assessment is more time-consuming but superior in detecting acute ischemia. The certainty with which stroke physicians prescribe or refrain from giving iv-tPA treatment to CT- versus MRI-examined patients has not previously been studied. The aim of the present study was to determine the effect of a primary imaging strategy of CT or MRI on clinicians' certainty to prescribe or refrain from giving iv-tPA to patients with suspected acute stroke. METHOD: Consecutive patients with suspected stroke were quasi-randomized to either CT- or MRI-based assessment before potential iv-tPA treatment. The influence of (1) the clinical findings and (2) the image findings, and (3) the certainty with which the stroke physician prescribed or refrained from giving iv-tPA treatment were assessed with visual analog scales (VAS). Predictors of treatment certainty were identified with a random-effect model. RESULTS: Four-hundred forty-four consecutive patients were quasi-randomized. MRI influenced the final treatment decision more than CT (P = .002). Compared with CT-examined patients (mean VAS score 8.6, SD ±1.6) stroke physicians were significantly more certain when prescribing or refraining from giving iv-tPA to MRI-examined patients (mean VAS score 9.0, SD ±1.2) (P = .014). No differences in modified Rankin scale or mortality were detected at 3 months in CT- versus MRI-examined iv-tPA-treated patients. CONCLUSIONS: Stroke physicians were significantly more certain when prescribing iv-tPA to MRI-examined stroke patients, and MRI influences the final treatment decision significantly more compared with CT, although no difference in mortality and functional outcome at 3 months was detected between CT- and MRI-examined patients treated with iv-tPA.

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.