Abstract
BackgroundDirect oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population.MethodsRetrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts.ResultsPatients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29–1.35) and a lower risk for bleeding (0.89; 0.88–0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82–2.03), apixaban (1.52; 1.46–1.58), and rivaroxaban (1.13; 1.10–1.17) but not for edoxaban (0.88; 0.74–1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83–0.88), apixaban (0.71; 0.70–0.73), and edoxaban (0.74; 0.68–0.81) but not for rivaroxaban (1.03; 1.01–1.04).ConclusionsThis study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.
Highlights
Direct oral anticoagulants (DOACs) are increasingly being used for the initial stroke prevention therapy but progressively substitute vitamin K antagonist (VKA) treatment in patients with nonvalvular atrial fibrillation (AF)
By analyzing a large proportion of all VKA and DOAC users with AF, the present study shows that VKA and DOAC users differ in their relative risks of stroke and bleeding and that these differences vary slightly depending on the individual DOAC therapy
These findings support the recommendation that the decision for VKA or DOAC treatment should depend on the patient’s individual stroke and bleeding risk [56]
Summary
Direct oral anticoagulants (DOACs) are increasingly being used for the initial stroke prevention therapy but progressively substitute vitamin K antagonist (VKA) treatment in patients with nonvalvular atrial fibrillation (AF). Interventionally designed pivotal studies for DOACs found a reduced (dabigatran, apixaban) or similar (rivaroxaban, edoxaban) risk of stroke and systemic embolism, and a reduced (apixaban, edoxaban) or similar (dabigatran, rivaroxaban) risk of bleeding [4,5,6,7] compared to the VKA warfarin, practical experience and observational studies showed different effects of DOACs. Shortly after approval, evidence emerged of an increased risk of bleeding in patients treated with dabigatran [8], which has been attributed to an undesirable increase in plasma concentration mostly in patients with renal failure [9]. Other international observational studies investigated the safety and the effectiveness of DOACs and showed similar risks for stroke, systemic embolism, and bleeding compared to warfarin, e.g., for dabigatran in a Danish cohort [11] and rivaroxaban in an American cohort [12]
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