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Objectives: To assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.Methods: We identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.Results: Among 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.Conclusion: In this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients. [ABSTRACT FROM AUTHOR]

Objectives: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).Methods: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.Results: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.Conclusions: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.Trial Registration Number: NCT00412984. [ABSTRACT FROM AUTHOR]