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A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease.

ABSTRACT: Background: Previous studies have investigated the association between a single marker of cerebral small vessel disease (SVD) and hemorrhagic transformation (HT). However, the effect of the total SVD burden on HT has not been evaluated yet. We aimed to investigate the association between the total SVD score and HT in ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Methods: Ischemic stroke patients with AF and/or RHD admitted within 7 days after onset were enrolled at two hospitals in China. The total SVD score was based on the presence of lacunes, extensive white matter hyperintensities, cerebral microbleeds, and moderate to severe enlarged perivascular spaces in the basal ganglia. One point was awarded for the presence of each marker, with the total SVD score ranging from 0 to 4 points. HT was assessed based on follow-up imaging scans during hospitalization and was classified according to the radiographic appearance and associated neurological deterioration. Results: Of 207 enrolled patients (mean age, 67.79 years; 58.9% female), 89 (43.0%) developed HT. The distribution of the total SVD score was significantly different between patients with and without HT in the univariate analysis (p = 0.04). After adjustment for confounders, a SVD score of 1 was independently associated with an increased risk of HT [odds ratio (OR), 3.23; 95% confidence interval (CI), 1.48-7.04; p = 0.003], while a SVD score ≥2 was inversely related to the occurrence of HT (OR, 0.41; 95% CI, 0.19-0.91; p = 0.03). These independent associations remained significant in the subgroups of hemorrhagic infarction and asymptomatic HT (all p < 0.05). Conclusions: In our study, the relationship between the total SVD score and HT was not linear, since the presence of only one marker of SVD was associated with an increased risk of HT, while the presence of two or more markers of SVD was a potential protective factor for HT. These results indicate the need to take the total SVD score into account, not only a single SVD marker, when assessing the risk of HT. Further studies with larger samples are required to validate these findings.

SUBMITTER: Wei C

PROVIDER: S-EPMC6667994 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe. Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation. Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0-3 for transient ischemic attack (TIA), 3-5 for small-sized AIS (<1.5 cm), and 7-9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded. Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities]. Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A). Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.

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A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease.

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