| 1. |
- Amarenco, Pierre, et al.
(författare)
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Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
- 2020
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 51:12, s. 3504-3513
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose:Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.Methods:In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.Results:Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001).Conclusions:In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171).
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| 2. |
- Andreasen, Charlotte, et al.
(författare)
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Incidence of Ischemic Stroke in Individuals with and without Aortic Valve Stenosis : A Danish Retrospective Cohort Study
- 2020
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Ingår i: Stroke. - 0039-2499. ; 51:1, s. 1364-1371
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods - All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results - In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among the controls compared with 30.4/1000 PY in patients with aortic valve stenosis, corresponding to a hazard ratio of 1.31 (95% CI, 1.28-1.34). In all age-groups, the incidence rates and relative risks were significantly increased in patients with aortic valve stenosis compared with controls, but the relative risk was greater for younger individuals (eg, age group, 18-45 years: hazard ratio, 5.94 [95% CI, 4.10-8.36]). In patients with aortic valve stenosis above 65 years of age, the risk of ischemic stroke was markedly lower after aortic valve replacement (30.3 versus 19.6/1000 PY before and after valve replacement). Among people with atrial fibrillation the incidence rate of ischemic stroke was 1.5 times higher when aortic valve stenosis was present (33.0/1000 PY versus 49.9/1000 PY). Conclusions - People with aortic valve stenosis have a significantly increased risk of ischemic stroke compared with age- and sex-matched controls. Future studies are warranted to explore whether antithrombotic therapy may be beneficial in some individuals.
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| 3. |
- Bhattacharya, Romit, et al.
(författare)
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Clonal Hematopoiesis Is Associated with Higher Risk of Stroke
- 2022
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Ingår i: Stroke. - 0039-2499. ; 29:2, s. 788-797
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke. Results: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. Conclusions: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.
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| 4. |
- Bosch, Jackie, et al.
(författare)
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Antihypertensives and Statin Therapy for Primary Stroke Prevention : A Secondary Analysis of the HOPE-3 Trial
- 2021
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 52:8, s. 2494-2501
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The HOPE-3 trial (Heart Outcomes Prevention Evaluation-3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. METHODS: Using a 2-by-2 factorial design, 12705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. RESULTS: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [H R], 0.80 [95% CI, 0.59-1.08]), ischemic stroke (H R, 0.80 [95% CI, 0.55-1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34-1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41-2.08]). Rosuvastatin significantly reduced strokes (H R, 0.70 [95% CI, 0.52-0.95]), with reductions mainly in ischemic stroke (H R, 0.53 [95% CI, 0.37-0.78]) but did not significantly affect hemorrhagic (H R, 1.22 [95% CI, 0.59-2.54]) or strokes of undetermined origin (H R, 1.29 [95% CI, 0.57-2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36-0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23-0.72]). CONCLUSIONS: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
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| 5. |
- Cadilhac, Dominique A., et al.
(författare)
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Stroke Learning Health Systems : A Topical Narrative Review With Case Examples
- 2023
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Ingår i: Stroke. - 0039-2499. ; 54:4, s. 1148-1159
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Forskningsöversikt (refereegranskat)abstract
- To our knowledge, the adoption of Learning Health System (LHS) concepts or approaches for improving stroke care, patient outcomes, and value have not previously been summarized. This topical review provides a summary of the published evidence about LHSs applied to stroke, and case examples applied to different aspects of stroke care from high and low-to-middle income countries. Our attempt to systematically identify the relevant literature and obtain real-world examples demonstrated the dissemination gaps, the lack of learning and action for many of the related LHS concepts across the continuum of care but also elucidated the opportunity for continued dialogue on how to study and scale LHS advances. In the field of stroke, we found only a few published examples of LHSs and health systems globally implementing some selected LHS concepts, but the term is not common. A major barrier to identifying relevant LHS examples in stroke may be the lack of an agreed taxonomy or terminology for classification. We acknowledge that health service delivery settings that leverage many of the LHS concepts do so operationally and the lessons learned are not shared in peer-reviewed literature. It is likely that this topical review will further stimulate the stroke community to disseminate related activities and use keywords such as learning health system so that the evidence base can be more readily identified.
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| 6. |
- Camen, Stephan, et al.
(författare)
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Cardiac Troponin I and Incident Stroke in European Cohorts : Insights From the BiomarCaRE Project
- 2020
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:9, s. 2770-2777
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce.Methods: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries.Results: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021).Conclusions: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.
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| 7. |
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| 8. |
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| 9. |
- Crump, Casey, et al.
(författare)
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Stroke risks in adult survivors of preterm birth : National cohort and cosibling study
- 2021
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Ingår i: Stroke. - 0039-2499. ; 52:8, s. 2609-2617
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort. Methods: A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. Results: In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12-1.43; P<0.001), and further stratified was 1.42 (1.11-1.81; P=0.005) for early preterm (22-33 weeks) and 1.22 (1.06-1.40; P=0.004) for late preterm (34-36 weeks), compared with full-term (39-41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: Adjusted hazard ratio, 1.42 [95% CI, 1.04-1.94]; any preterm: 1.15 [0.97-1.35]) and ischemic stroke (early preterm: Adjusted hazard ratio, 1.33 [95% CI, 0.87-2.03]; any preterm: 1.31 [1.07-1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families. Conclusions: In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.
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| 10. |
- Darehed, David, 1986-, et al.
(författare)
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In-hospital delays in stroke thrombolysis : every minute counts
- 2020
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 51:8, s. 2536-2539
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Intravenous thrombolysis is a well-established treatment for acute ischemic stroke. Our aim was to quantify the effect of each minute delay in door-to-needle time (DNT) on 90-day survival, intracerebral hemorrhagic complication <36 hours, and functional outcomes at 3 months, in routine clinical practice.Methods: Our nationwide registry-based study included 14 132 adult patient admissions with ischemic stroke receiving intravenous thrombolysis from 2010 to 2017. Outcomes were analyzed using multivariable logistic regression, adjusting for potential confounders.Results: Median DNT was 47 minutes, with an improvement from 65 to 38 minutes during the study. Median age was 74 years, and median National Institutes of Health Stroke Scale 8 points. We found a significant impact of each minute delay in DNT with reduced odds of survival by 0.6%, increased odds of intracerebral hemorrhagic and worse activities of daily living by 0.3%, and worse living conditions and mobility by 0.4%.Conclusions: Improving DNT is a key factor in achieving good outcomes after stroke. We estimate that in Sweden alone in 2017, compared with 2010, the shorter DNT achieved have saved 38 lives, avoided 8 intracerebral hemorrhagic transformations, and spared, respectively, 36, 51, and 52 patients from a worsening in activities of daily living, living conditions, and mobility. DNT is sensitive for interventions and should be targeted in quality improvement efforts.
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