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  • Ovid Technologies (Wolters Kluwer Health)  (5)
  • Silver, Brian  (5)
  • 1
    Online Resource
    Online Resource
    Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Vol. 136, No. 10 ( 2017-09-05), p. 907-916
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 10 ( 2017-09-05), p. 907-916
    Abstract: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.117.028566
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1466401-X
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  • 2
    Online Resource
    Online Resource
    C-Reactive Protein as a Prognostic Marker After Lacunar Stroke : Levels of Inflammatory Markers in the Treatment of Stroke Study
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 3 ( 2014-03), p. 707-716
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 3 ( 2014-03), p. 707-716
    Abstract: Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Methods— Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Results— Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP 〉 4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15–4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14–3.67). There was no interaction with randomized antiplatelet treatment. Conclusions— Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00059306.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.113.004562
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Troponin Improves the Yield of Transthoracic Echocardiography in Ischemic Stroke Patients of Determined Stroke Subtype
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Stroke Vol. 49, No. 11 ( 2018-11), p. 2777-2779
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 11 ( 2018-11), p. 2777-2779
    Abstract: Transthoracic echocardiography (TTE) is widely used in the ischemic stroke setting. In this study, we aim to investigate the yield of TTE in patients with ischemic stroke and known subtype and whether the admission troponin level improves the yield of TTE. Methods— Data were abstracted from a single-center prospective ischemic stroke database for 18 months and included all patients with ischemic stroke whose etiologic subtype could be obtained without the need of TTE. Unadjusted and adjusted regression models were built to determine whether positive cardiac troponin levels (≥0.1 ng/mL) improve the yield of TTE, adjusting for demographic and clinical characteristics. Results— We identified 578 patients who met the inclusion criteria. TTE changed clinical management in 64 patients (11.1%), but intracardiac thrombus was detected in only 4 patients (0.7%). In multivariable models, there was an association between TTE changing management and positive serum troponin level (adjusted odds ratio, 4.26; 95% CI, 2.17–8.34; P 〈 0.001). Conclusions— In patients with ischemic stroke, TTE might lead to a change in clinical management in ≈1 of 10 patients with known stroke subtype before TTE but changed acute treatment decisions in 〈 1 percent of patients. Serum troponin levels improved the yield of TTE in these patients.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.118.022477
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1467823-8
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  • 4
    Online Resource
    Online Resource
    Ischemic Stroke Risk After Acute Coronary Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Journal of the American Heart Association Vol. 5, No. 7 ( 2016-07-06)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 7 ( 2016-07-06)
    Abstract: Prior studies show an increased risk of ischemic stroke ( IS ) after myocardial infarction; however, there is limited evidence on long‐term risk and whether it is directly related to cardiac injury. We hypothesized that the risk of IS after acute coronary syndrome is significantly higher if there is evidence of cardiac injury, such as ST‐segment elevation myocardial infarction ( STEMI ) or non‐ STEMI , than when there is no evidence of cardiac injury, such as in unstable angina. Methods and Results Administrative claims data were obtained from all emergency department encounters and hospitalizations at California's nonfederal acute care hospitals between 2008 and 2011. Patients with STEMI , non‐STEMI, and unstable angina were identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The primary outcome was IS during 2 years of follow‐up. Unadjusted and adjusted Cox proportional hazards models were used to determine the association between acute coronary syndrome subtype and IS risk. We identified 73 059 patients with a diagnosis of STEMI (n=26 427), non‐STEMI (n=39 833), or unstable angina (n=6819) during the study period. In the fully adjusted models that included potential confounders such as atrial fibrillation and congestive heart failure, the risk of IS was higher with STEMI (hazard ratio 4.17, 95% CI 3.00–5.83; P 〈 0.001) and non‐STEMI (hazard ratio 3.73, 95% CI 2.68–5.19, P 〈 0.001) compared with unstable angina. Conclusions Non‐STEMI and STEMI confer an equally increased risk of IS . Studies exploring IS mechanisms in cardiac patients are needed to improve and tailor stroke prevention strategies.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.115.002590
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2653953-6
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  • 5
    Online Resource
    Online Resource
    Whole-Genome Sequencing Association Analyses of Stroke and Its Subtypes in Ancestrally Diverse Populations From Trans-Omics for Precision Medicine Project
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 3 ( 2022-03), p. 875-885
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 3 ( 2022-03), p. 875-885
    Abstract: Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid). Methods: Whole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis. Results: In the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance ( P 〈 5.00×10 −9 ) and 4 novel loci at genome-wide significance ( P 〈 5.00×10 −8 ), all of which need confirmation in independent studies. Lead variants in all 5 loci are low-frequency but are more common in non-European populations. An aggregation of synonymous rare variants within the gene C6orf26 demonstrated suggestive evidence of association for hemorrhagic stroke ( P 〈 3.11×10 −6 ). By meta-analyzing European ancestry samples in TOPMed and UK BioBank, we replicated several previously reported stroke loci including PITX2 , HDAC9 , ZFHX3 , and LRCH1 . Conclusions: We represent the first association analysis for stroke and its subtypes using whole-genome sequencing data from ancestrally diverse populations. While our findings suggest the potential benefits of combining whole-genome sequencing data with populations of diverse genetic backgrounds to identify possible low-frequency or ancestry-specific variants, they also highlight the need to increase genome coverage and sample sizes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.031792
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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