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The article describes the findings of the initial studies on the treatment with direct oral anticoagulants (DOACs) (1). Using a health insurance claims-based data following market entry, Ujeyl and co-workers compared the incidence rate of clinical events with DOACs to those with phenprocoumon (2). As in the pivotal trials, significantly less bleeding occurred with dabigatran and apixaban, but not with rivaroxaban. Gastrointestinal bleeding occurred 21% more frequently with dabigatran, and 28% with rivaroxaban, but intracranial bleeding occurred less frequently (rivaroxaban, –61%; dabigatran, –43%) (2). Surprisingly, ischemic stroke occurred 84% ​​more frequently with apixaban, and the all-cause mortality was higher with rivaroxaban than with phenprocoumon (2).

Which causes can explain this discrepancy? This may be due at least in part to a faulty or too superficial therapy with DOACs, which is still supported by the summary of product characteristics (“no monitoring”) (3). Regular laboratory controls (liver, kidney) are required in order to allow early detection of dysfunctions and possible adaptations of the therapy strategy. Also, metabolism of DOACs in older patients with co-medications can be profoundly altered. Therefore, regular quantification of DOAC levels should be carried out using anti-Xa activity assays (for all except dabigatran, for which the ecarin clotting time [ECT]/ diluted thrombin time [dTT] should be used). It would be helpful if consensus recommendations for actions were developed, to determine when, with which tests, and on the basis of which target values ​​DOAC monitoring should be carried out, and what are the consequences of deviations from the target range (3).

As an aside, it should be noted that the incidence of intracranial bleeding among vitamin K antagonists is more than halved if the target INR range is chosen to be between 1.8–2.4 for atrial fibrillation and venous thromboembolism. At INR values ​​of 2.5–3, the probability of intracranial bleeding is twice as high as thrombosis protection (4).

DOI: 10.3238/arztebl.2019.0220b

Prof. Dr. med. Dr.-Ing. Holger Kiesewetter, PD Dr. med. Berthold Hoppe

Hämostaseologicum MVZ GbR, Berlin, Germany

H.Kiesewetter@haemostaseologicum.com

Conflict of interest statement

The author declares that no conflict of interest exists.

1.
Altiok E, Marx N: Oral anticoagulation—update on anticoagulation with vitamin K antagonists and non–vitamin K–dependent oral anticoagulants. Dtsch Arztebl Int 2018; 115: 776–83 VOLLTEXT
2.
Ujeyl M, Köster I, Wille H, et al.: Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation. Eur J Clin Pharmacol 2018. [Epub ahead of print] CrossRef MEDLINE
3.
Der Arzneimittelbrief: Orale Antikoagulanzien: besseres Medikationsmanagement erforderlich. www.der-arzneimittelbrief.de/de/Artikel.aspx?J=2018&S=41 (last accessed on 26. February 2019).
4.
Hylek EM, Singer DE: Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897–902 MEDLINE
1. Altiok E, Marx N: Oral anticoagulation—update on anticoagulation with vitamin K antagonists and non–vitamin K–dependent oral anticoagulants. Dtsch Arztebl Int 2018; 115: 776–83 VOLLTEXT
2.Ujeyl M, Köster I, Wille H, et al.: Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation. Eur J Clin Pharmacol 2018. [Epub ahead of print] CrossRef MEDLINE
3.Der Arzneimittelbrief: Orale Antikoagulanzien: besseres Medikationsmanagement erforderlich. www.der-arzneimittelbrief.de/de/Artikel.aspx?J=2018&S=41 (last accessed on 26. February 2019).
4.Hylek EM, Singer DE: Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897–902 MEDLINE

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