BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT ; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

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Osteocalcin, a 49-amino acid, gamma-carboxyglutamic acid-containing protein produced by the osteoblast, has been shown in laboratory animals to be a better marker of bone turnover than alkaline phosphatase. To determine serum osteocalcin levels in growing pigs, we isolated pure porcine osteocalcin and developed a double-antibody RIA. To evaluate the effects of dietary Ca and P levels on serum osteocalcin, 36 individually penned crossbred pigs (19.5 kg initial BW) were fed fortified corn-soybean meal diets (.95% lysine) containing four levels of Ca (.42, .66, .90, 1.14%) and P (.35, .55, .75, .95%) in a 30-d test. Increasing dietary Ca and P improved body weight gain quadratically (P < .02). Most bone traits improved quadratically (P < .05) with increasing Ca and P. Pigs were bled on d 0, 10, 20, and 30 to determine serum levels of alkaline phosphatase, 1,25-dihydroxyvitamin D3, and osteocalcin. Osteocalcin decreased (P < .02) linearly with increasing Ca and P on d 10, 20, and 30. However, this effect was much more pronounced on d 20 and 30. Alkaline phosphatase decreased with the first incremental increase in dietary Ca and P, but was not affected by higher levels on any day measured. Osteocalcin was inversely correlated with growth rate (r = -.54, P < .01), bone strength (r = -.57, P < .01), metacarpal ash (r = -.29, P < .10), femur ash (r = -.60, P < .01), and femur ash weight (r = -.65, P < .01). Similar results were found for 1,25-dihydroxyvitamin D3. Alkaline phosphatase was not correlated with performance or most bone traits on d 30. Based on this model, these results suggest that serum osteocalcin and 1,25-dihydroxyvitamin D3 are better predictors of bone mineralization and(or) turnover in pigs than serum alkaline phosphatase.