The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with ...antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions.
In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging.
We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval CI, 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (22 patients 5.7% vs. 20 patients 11.3%; relative risk, 0.51; 95% CI, 0.29 to 0.91; P=0.04), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P=0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure.
Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894 .).
Background and purpose
Recurrent ischemic stroke (IS) or TIA is frequent with a considerable variation in incidence and mortality across populations. Current data on stroke recurrence and mortality ...are useful to examine trends, risk factors, and treatment effects. In this study, we calculated the incidence of recurrent IS or TIA in a hospital‐based stroke population in Western Norway, investigated recurrence factors, and estimated the effect of recurrence on all‐cause mortality.
Methods
This prospective cohort study registered recurrence and mortality among 1872 IS and TIA survivors admitted to the stroke unit at Haukeland University Hospital between July 2007 and December 2013. Recurrence and death until September 1, 2016, were identified by medical chart review. Cumulative incidences of recurrence were estimated with a competing risks Cox model. Multivariate Cox models were used to examine recurrence factors and mortality.
Results
During follow‐up, 220 patients had 277 recurrent IS or TIAs. The cumulative recurrence rate was 5.4% at 1 year, 11.3% at 5 years, and 14.2% at the end of follow‐up. Hypertension (HR = 1.65, 95% CI 1.21‐2.25), prior symptomatic stroke (HR = 1.63, 95% CI 1.18‐2.24), chronic infarcts on MRI (HR = 1.48, 95% CI 1.10‐1.99), and age (HR 1.02/year, 95% CI 1.00‐1.03) were independently associated with recurrence. A total of 668 (35.7%) patients died during follow‐up. Recurrence significantly increased the all‐cause mortality (HR = 2.55, 95% CI 2.04‐3.18).
Conclusions
The risk of recurrent IS stroke or TIA was modest in our population and was associated with previously established risk factors. Recurrence more than doubled the all‐cause mortality.
Abstract
Background
Several studies have shown that stroke mimics occur more often among young patients. Our aims were to identify the common mimics in young patients under the age of 60 years who ...received thrombolysis, to analyze the risk of hemorrhage after treatment with thrombolysis, and to identify risk factors and clinical parameters that might identify mimics in this group.
Methods
Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with acute ischemic stroke. Patients diagnosed with either acute cerebral ischemia or transient ischemic attack were categorized as stroke group, and patients with any diagnosis other than ischemic stroke or transient ischemic attack as mimics group. Patients were grouped post-hoc into young (< 60 years) and old (≥ 60 years). Logistic regression analyses were performed with mimics vs. stroke as dependent variable to identify predictors of mimics.
Results
Of the 1091 patients included in the trial, 211 patients (19.3%) were under the age of 60 years. Out of the 1091 patients, 434 (39.8%) were female, median age 77 years (18–99 years), and median NIHSS was 4. Sixty-nine patients (32.7%) out of the 211 patients under the age of 60 were diagnosed as mimic. Mimics were significantly more frequent among the young (OR = 3.3, 32.7% vs. 12.8%, p = < 0.001). The most frequent mimics diagnoses among patients under 60 years of age were migraine (11.8%), no definite diagnosis (11.4%) and peripheral vertigo (3.3%). Mimics were independently associated with age < 50 years (OR = 4.97, p = < 0.001), not currently working/studying (OR = 3.38, p = 0.002) and not having aphasia on admission (OR = 2.95, p = 0.025). None of the mimics under the age of 60 years had symptomatic or asymptomatic intracerebral hemorrhage as a complication to thrombolysis.
Conclusion
We found significantly more mimics in the young, of which migraine was the most predominant diagnosis. Thrombolysis with alteplase or tenecteplase did not cause ICH in any mimics under 60 years.
Background: Underlying malignancy can cause ischemic stroke in some patients. Mechanisms include the affection of the coagulation cascade, tumor mucin secretion, infections and nonbacterial ...endocarditis. The release of necrotizing factor and interleukins may cause inflammation of the endothelial lining, creating a prothrombotic surface that triggers thromboembolic events, including stroke. The aims of this study were to assess the occurrence of cancer in patients who had recently suffered an ischemic stroke and to detect possible associations between stroke and cancer subtypes. Methods: All ischemic stroke patients registered in the Norwegian Stroke Research Registry (NORSTROKE) as part of the ongoing Bergen NORSTROKE study were included. Blood samples were obtained on admission. Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, and the severity of stroke was defined according to the National Institute of Health Stroke Scale score. Information about cancer disease after stroke was obtained from patient medical records and The Cancer Registry of Norway. Results: From a total of 1,282 ischemic stroke patients with no history of cancer, 55 (4.3%) patients were diagnosed with cancer after stroke. The median time from stroke onset to cancer diagnosis was 14.0 months (interquartile range 6.2-24.5). Twenty-three (41.8%) patients were diagnosed with cancer within 1 year and 13 (23.6%) within 6 months. The most common cancer type was lung cancer (19.0%). By Cox regression analysis, cancer after stroke was associated with elevated D-dimer levels on admittance (p < 0.001), age (p = 0.01) and smoking (p = 0.04). Conclusions: Cancer-associated stroke is rare, and routine investigation for cancer seems unwarranted in acute ischemic stroke. However, in stroke patients with elevated levels of blood coagulation factors, C-reactive protein, higher age and a history of smoking, underlying malignancy should be considered. Our study suggests that an unknown stroke etiology does not predict malignancy.
Background The optimal dose of tenecteplase in acute ischemic stroke remains to be defined. We present a pooled analysis of the 2 NOR-TESTs (Norwegian Tenecteplase Stroke Trials) exploring the ...efficacy and safety of tenecteplase, 0.4 mg/kg. Methods and Results We retrospectively reviewed 2 PROBE (Prospective Randomized Open, Blinded End-point) trials, NOR-TEST and NOR-TEST 2A. Patients were randomized to either tenecteplase, 0.4 mg/kg, or alteplase, 0.9 mg/kg. The primary end point was favorable functional outcome at 3 months (modified Rankin Scale score, 0-1) or return to baseline if prestroke modified Rankin Scale score was 2. Secondary end points included favorable functional and clinical outcome and safety data. The pooled analysis includes patients with National Institutes of Health Stroke Scale score ≥6 from both trials and an additional post hoc analysis of patients with National Institutes of Health Stroke Scale score ≤5 from NOR-TEST. The per-protocol analysis contains 483 patients, of whom 235 were assigned to tenecteplase and 248 were assigned to alteplase. In per-protocol analysis, functional outcome was better in the alteplase arm with cutoff modified Rankin Scale score of 2 (odds ratio OR, 0.52 95% CI, 0.33-0.80;
=0.003) and expressed by ordinal shift analysis (OR, 1.64 95% CI, 1.17-2.28;
=0.004). Mortality at 3 months was higher in the tenecteplase arm (OR, 2.48 95% CI, 1.20-5.10;
=0.01). Mortality and intracranial hemorrhage rates were higher in the severe stroke group randomized to tenecteplase, whereas these rates were similar for alteplase and tenecteplase in moderate and mild stroke. Conclusions Tenecteplase, 0.4 mg/kg, is unsafe in moderate and severe stroke, and the risk of death and intracranial hemorrhage probably increases with stroke severity. A lower tenecteplase dose should be tested in future trials. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01949948, NCT03854500.
Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral ...artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients.
First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT.
During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD.
FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients.
ClinicalTrials.gov NCT01597453.
Background:
Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque ...neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia.
Methods:
Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months.
Results:
We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization.
Conclusions:
In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization.
Clinical Trial Registration:
ClinicalTrial.gov
, identifier NCT02759653.
Background and Purpose
We aimed to evaluate factors associated with neurological worsening among patients with lacunar or non‐lacunar infarction admitted within 3 hours and between 3 and 24 hours ...after stroke onset.
Methods
All patients admitted to Haukeland university hospital between 2006 and 2016 with acute cerebral infarction on MRI and admission within 24 hours were included. Repeated National Institute of Health Stroke Scale (NIHSS) scoring was performed in all patients whenever possible. Neurological worsening during the hospital stay was defined as NIHSS score increase ≥3 compared to NIHSS score on admission.
Results
In patients with lacunar infarction admitted within 3 hours of onset, neurological worsening was associated with low NIHSS score on admission, low body temperature, and leukoaraiosis, whereas only internal carotid artery stenosis or occlusion was associated with neurological worsening in non‐lacunar infraction. For patients admitted 3‐24 hours after onset, neurological worsening was associated with low body temperature, high systolic blood pressure, and short time from onset to admission in patients with lacunar infarction, whereas high systolic blood pressure, high NIHSS score on admission, middle cerebral artery occlusion, and high blood glucose were associated with neurological worsening in patients with non‐lacunar infarction (all P < 0.05).
Conclusions
Lacunar infarctions with minor neurological deficits within 3 hours of stroke onset are at high risk of neurological worsening especially if concomitant low body temperature and leukoaraiosis.
The burden of hospital readmission after stroke is substantial, but little knowledge exists on factors associated with long-term readmission after stroke. In a cohort comprising patients with ...ischemic stroke and transient ischemic attack (TIA), we examined and compared factors associated with readmission within 1 year and first readmission during year 2-5.
Patients with ischemic stroke or TIA who were discharged alive between July 2007 and October 2012, were followed for 5 years by review of medical charts. The timing and primary cause of the first unplanned readmission were registered. Cox regression was used to identify independent risk factors for readmission within 1 year and first readmission during year 2-5 after discharge.
The cohort included 1453 patients, of whom 568 (39.1%) were readmitted within 1 year. Of the 830 patients that were alive and without readmission 1 year after discharge, 439 (52.9%) were readmitted within 5 years. Patients readmitted within 1 year were older, had more severe strokes, poorer functional outcome, and a higher occurrence of complications during index admission than patients readmitted during year 2-5. Cardiovascular comorbidity and secondary preventive treatment did not differ between the two groups of readmitted patients. Higher age, poorer functional outcome, coronary artery disease and hypertension were independently associated with readmission within both 1 year and during year 2-5. Peripheral artery disease was independently associated with readmission within 1 year, and atrial fibrillation was associated with readmission during year 2-5.
More than half of all patients who survived the first year after stroke without any readmissions were readmitted within 5 years. Patients readmitted within 1 year and between years 2-5 shared many risk factors for readmission, but they differed in age, functional outcome and occurrence of complications during the index admission.
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