Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

BACKGROUND AND OBJECTIVES: Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of antithrombotic regimens after the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOACs with and without an alternative antithrombotic regimen and determine the risk factors of recurrent ischemic stroke while on anticoagulation. METHODS: In a population-based, propensity score-weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOACswitch), or addition of antiplatelet agents, with those of unchanged DOAC regimen (DOACsame) among patients with nonvalvular atrial fibrillation (NVAF) who developed the first ischemic stroke despite a DOAC from January 1, 2015, to December 31, 2020, in Hong Kong. The primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome, and death. We performed competing risk regression analyses to compare the clinical endpoints and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model. RESULTS: During the 6-year study period, among 45,946 patients with AF on a DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite a DOAC. A total of 2,337 patients with NVAF were included in the final analyses. Compared with DOACsame, warfarin (aHR 1.96, 95% CI 1.27-3.02, p = 0.002) and DOACswitch (aHR 1.62, 95% CI 1.25-2.11, p < 0.001) were associated with an increased risk of recurrent ischemic stroke. In the DOACsame group, adjunctive antiplatelet agent was not associated with a reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke. DISCUSSION: In patients with NVAF with ischemic stroke despite a DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not seem to reduce ischemic stroke relapse. Because diabetes mellitus, the use of CYP/P-gp modulators, and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate whether strict glycemic control, DOAC level monitoring, and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF experiencing an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.

Morphometric changes in the hoof capsule of Criollo foals from birth to weaning / Alterações morfológicas na capsula do casco em potros Crioulos do nascimento ao desmame

ABSTRACT: South America has numerous Criollo horse breeding farms; however, information on foal hoof growth is still limited and identifying the ideal periods to apply corrective trimming is a frequent concern for horse owners. In the present study, a morphometric analysis of hoof growth was performed on 46 Criollo foals from birth to weaning (0-8 months). Results showed that hoof growth rate was higher in the first four months followed by a decrease until the eighth month. Average growth rate of the hoof was 0.21cm per month, whereas that of the heel was 0.14cm per month. However, no significant differences were observed between medial and lateral heel length or between limbs. Coronary band perimeter and solar width showed an average increase of 0.97cm and 0.46cm per month, respectively, and were significantly correlated (r=0.99, P≤0.01). The characteristic most positively correlated to biometric variables was foal age, followed by solar width, toe length, and coronary band perimeter. In conclusion, hoof length increase in Criollo foals was more intensive during the first four months of life.

RESUMO: A América do Sul possui um grande número de criatórios da raça Crioula, no entanto, há uma carência de informações sobre o desenvolvimento natural dos cascos dos potros, tornando a identificação de períodos ideais para o casqueamento corretivo uma dúvida frequente entre os criadores. Portanto, o objetivo deste estudo foi realizar a biometria natural (do nascimento aos 8 meses) no casco de 46 potros da raça Crioula. Os resultados indicaram uma taxa de crescimento mais rápido nos primeiros 4 meses, com subsequente desaceleração até o desmame. O crescimento médio do casco foi em média 0,21cm mo-1, enquanto o comprimento do talão foi de 0,14cm mo-1. Não foram observadas diferenças significativas no equilíbrio médio/lateral do casco ou entre os membros durante o período experimental. O perímetro da banda coronária e a largura solar do casco apresentaram um crescimento médio de 0,97 e 0,46cm mo-1, respectivamente, e foram altamente correlacionados (r=0,99, P≤0,01). A idade dos potros foi a característica mais correlacionada positivamente, seguida da largura solar, do comprimento do casco e do perímetro da banda coronária. Nós concluímos que o crescimento do casco em potros da raça Crioula foi mais intenso durante os quatro primeiros meses de vida.