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  • 1
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    High Sensitivity Detection of Active Botulinum Neurotoxin by Glyco-Quantitative Polymerase Chain-Reaction
    American Chemical Society (ACS) ; 2014
    In:  Analytical Chemistry Vol. 86, No. 5 ( 2014-03-04), p. 2279-2284
    Details
    In: Analytical Chemistry, American Chemical Society (ACS), Vol. 86, No. 5 ( 2014-03-04), p. 2279-2284
    Type of Medium: Online Resource
    ISSN: 0003-2700 , 1520-6882
    URL: Article
    DOI: 10.1021/ac500262d
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2014
    detail.hit.zdb_id: 1483443-1
    detail.hit.zdb_id: 1508-8
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  • 2
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    Intracranial Hemorrhage in the TST Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 2 ( 2022-02), p. 457-462
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 2 ( 2022-02), p. 457-462
    Abstract: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of 〈 70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03] , respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of 〈 70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.121.035846
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
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    Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol 〈70 mg/dL During 5 Years After Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 4 ( 2020-04), p. 1231-1239
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 4 ( 2020-04), p. 1231-1239
    Abstract: The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 〈 70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque 〉 4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to 〈 70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90–110 mg/dL, 2.3–2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of 〈 70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.028718
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 4
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    More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL 〈70 mg/dL After a Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 8 ( 2023-08), p. 1993-2001
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 8 ( 2023-08), p. 1993-2001
    Abstract: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol 〈 70 mg/dL is more effective when LDL is reduced 〉 50% from baseline rather than 〈 50% from baseline has not been investigated. METHODS: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of 〈 70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2–6] per patient) during 3.9 years (interquartile range, 2.1–6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients in the lower target group who had 〉 50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had 〈 50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P 〈 0.001 for both). In the 〈 70 mg/dL target group, patients with 〉 50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43–0.88]; P =0.007) and patients with 〈 50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73–1.26]; P =0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of 〈 70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu ; Unique identifier: EUDRACT2009-A01280-57.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.123.042621
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
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    Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants
    American Medical Association (AMA) ; 2023
    In:  JAMA Neurology Vol. 80, No. 3 ( 2023-03-01), p. 233-
    Details
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 3 ( 2023-03-01), p. 233-
    Abstract: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). Objective To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. Design, Setting, and Participants This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021. Exposures Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. Main Outcomes and Measures The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses. Results Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion. Conclusions and Relevance In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    URL: Article
    DOI: 10.1001/jamaneurol.2022.4782
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 6
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    Abstract WP98: Utilization Of Perfusion Imaging For Acute Ischemic Stroke: Secular Trends And Effects On Outcomes Of Endovascular Treatment
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. Suppl_1 ( 2023-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Introduction: Perfusion imaging (PI) could guide decision-making for endovascular treatment (EVT) of acute ischemic stroke (AIS). However, PI was underused even in the US before the pivotal EVT trials proved its usefulness in 2018. This study aimed to describe the secular trends of PI utilization and investigate the effectiveness of PI-based EVT in real-world practice. Methods: Using a prospective multicenter (n=17) stroke registry in South Korea, we identified patients with AIS who presented within 24 hours from onset between 2011 and 2021. The study period was divided into 3 epochs: 2011-2014, 2015-2017, and 2018-2021. The study population was divided into the early (arrival within 6 hours) and late window (6-24 hours) groups. Results: A total of 51,650 patients (15,654 patients in 2011-2014, 14,432 patients in 2015-2017, and 21,564 patients in 2018-2021) were analyzed. Utilization of PI decreased in the overall population and early window group ( P trend 〈 0.001); 43.3% and 54.1% in 2011-2014, 40.1% and 44.1% in 2015-2017, and 38.4% and 40.2% in 2018-2021, respectively; but increased in the late window group ( P trend 〈 0.001); 31.3% in 2011-2014, 35.7% in 2015-2017, and 36.5% in 2018-2021. Of 10,872 patients with anterior large-vessel occlusion (aLVO), the EVT rate was not different between patients with and without PI (48.7% vs. 46.6%, P =0.08) in the early window but higher in those with PI than without PI in the late window (29.8% vs. 18.7%, P 〈 0.001). The EVT outcome (3-month mRS 0-2) was not different between patients with and without PI in the early window (44.1% vs. 41.8%, P =0.21) and late window (38.4% vs. 39.2%, P =0.81). Propensity score analysis and instrumental variable analysis with PI rate per center as an instrument will be performed to adjust imbalances between patients with and without PI. Conclusion: Between 2011 and 2021 in South Korea, PI utilization has decreased in patients arriving within 6 hours from onset but has increased in those arriving between 6 and 24 hours. Among patients with aLVO, PI likely increased the EVT rate in the late window but did not in the early window. PI utilization did not seem to affect the EVT outcomes, but in-depth analysis is required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.54.suppl_1.WP98
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 7
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    David G. Sherman Lecture Award: 15-Year Experience of the Nationwide Multicenter Stroke Registry in Korea
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 9 ( 2022-09), p. 2976-2987
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 9 ( 2022-09), p. 2976-2987
    Abstract: The expected growth of stroke burden in Korea in early 2000s led to the initiation of a government-funded clinical research project with the goal of development and implementation of national stroke guidelines. The CRCS-K (Clinical Research Collaboration for Stroke in Korea) began as a part of this project. For stroke epidemiology and quality of care research, the CRCS-K developed a multicenter, prospective, stroke registry and began collection of data in 2008. Now, about 100 000 cases have been registered at 17 university hospitals or regional stroke centers and about 200 articles have been published based on the registry experience. The analysis of the 10-year secular trends showed overall improvement of stroke care and outcomes and areas for improvement. This large-scale, high-quality dataset provides opportunities to explore and compare treatment disparities using the comparative effectiveness research methods, design and conduct a registry-based randomized clinical trial, connect the registry data with other data sources including the national claims data and neuroimaging or genetic data, and collaborate with other international researchers. An international stroke registry consortium may be a viable future direction.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.039212
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 8
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    Abstract 44: Impact Of Novel Oral Anticoagulant Use On Secular Trend Of Vascular Events Or Death After Atrial Fibrillation-related Acute Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. Suppl_1 ( 2023-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Introduction: Now novel oral anticoagulants (NOAC) are strongly recommended for secondary stroke prevention in patients with atrial fibrillation (AF). However, it remains unclear to what extent the introduction of NOACs improved clinical outcomes in real-world practice. Methods: Using a nationwide prospective multi-center stroke registry database, we identified consecutive AIS patients with AF enrolled between Jan 2011 and Dec 2019, and analyzed one-year clinical events and NOAC prescription at discharge. The primary outcome was the composite of stroke, myocardial infarction, and all-cause death. To assess the mediation effect of NOAC on the outcomes, we performed natural effect models according to the calendar year. The exposure-mediator analysis, exposure-outcome analysis, and mediator-outcome analysis were performed using multivariate regression analysis according to the characteristics of the variables. Results: We analyzed 12,500 patients (mean age, 74.4 years; 51.3% male; median NIHSS at presentation, 8). From 2011 to 2019, the cumulative one-year incidence of the primary composite outcome (28.3% to 22.1%), all-cause mortality (23.8% to 17.9%), and stroke recurrence (8.3% to 5.1%) significantly decreased, while the NOAC prescription rate at discharge increased (0% to 75.6%). One-year increase in the calendar year was independently associated with a delayed occurrence of primary composite outcomes (Step 1: adjusted Time Ratio (aTR), 1.10; 95% confidence interval, 1.07-1.14) and with an increased NOAC prescription rate (Step 2: adjusted odds ratio, 2.20; 2.14-2.27). Increase in the NOAC prescription rate was significantly associated with the delayed occurrence of primary composite outcome (Step 3: aTR, 3.80; 3.15-4.58). However, after controlling for the NOAC prescription rate (mediator), the calendar year was no longer associated with the primary composite outcomes. (Step 4: aTR, 0.78; 95% CI 0.60-1.03). Thus, our results indicate full mediation of NOAC prescription in the association between the calendar year and primary composite outcomes. Conclusion: The reduced risk of major vascular events or death over time in AIS patients with AF was fully mediated by the increase in NOAC use.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.54.suppl_1.44
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 9
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    Abstract WMP97: Symptomatic Steno-occlusion Of Major Cerebral Arteries And Stroke Recurrence In Acute Ischemic Stroke Patients With Atrial Fibrillation
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. Suppl_1 ( 2023-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Introduction: There is lack of knowledge on whether symptomatic steno-occlusion (SYSO), common in acute ischemic stroke (AIS) patients with atrial fibrillation (AF), could increase the long-term risk of stroke recurrence in these patients. Methods: From a prospective cohort of patients with AIS and AF enrolled in 14 centers between Oct 2017 and Dec 2018, we identified patients who underwent MR angiography during hospitalization and completed 3-year follow-up including death during follow-up. SYSO was defined as (1) ≥ 50% stenosis or occlusion of cerebral arteries relevant to acute infarction or (2) any residual stenosis after endovascular treatment. Using cause-specific hazard models with non-stroke death as a competing risk, the risk of any recurrent stroke and recurrent ischemic stroke was estimated according to SYSO, respectively. Results: A total of 889 patients (mean age, 74.4 years; men, 54.6 %; median NIHSS, 6) were analyzed for this study. During the median 1096 days of follow-up, 152 any recurrent strokes, 142 recurrent ischemic strokes, and 208 deaths were observed. Patients with SYSO, compared to those without, were more likely to be older, be female, have hypertension, diabetes and history of stroke/TIA, and be on antiplatelets at discharge and were less likely to be on anticoagulants at discharge ( p 〈 .05). The cumulative incidence of recurrent stroke in patients with and without SYSO was 25.2% and 8.3% at 1 month, 33.1% and 9.9% at 1 year, and 41.8% and 13.1% at 3 years, respectively ( p 〈 .001). With adjusting age, sex, hypertension, diabetes, history of stroke/TIA, discharge antiplatelets, and discharge anticoagulants, SYSO increased the risk of any stroke recurrence (adjusted hazard ratio [95% confidence interval]; 3.02 [2.18-4.20] ; p 〈 .001) and ischemic stroke recurrence (3.20 [2.28-4.51]; p 〈 .001). Conclusions: SYSO in AIS patients with AF substantially increased the risk of recurrent stroke by a 3-fold or more. Accordingly, SYSO should be considered in stratifying the risk of recurrence in AIS patients with AF.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.54.suppl_1.WMP97
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 10
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    Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis
    SAGE Publications ; 2023
    In:  International Journal of Stroke Vol. 18, No. 7 ( 2023-08), p. 812-820
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 18, No. 7 ( 2023-08), p. 812-820
    Abstract: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23–0.60, p  〈  0.001) and death (HR: 0.35, 95% CI: (0.19–0.63), p  〈  0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31–21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/17474930231158211
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2211666-7
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