Vitamin-K-antagonist phenprocoumon versus low-dose direct oral anticoagulants (DOACs) in patients with atrial fibrillation: a real-world analysis of German claims data

Lisette Warkentin; Susann Hueber; Barthold Deiters; Florian Klohn; Thomas Kühlein

doi:10.1186/s12959-022-00389-9

Vitamin-K-antagonist phenprocoumon versus low-dose direct oral anticoagulants (DOACs) in patients with atrial fibrillation: a real-world analysis of German claims data

Thromb J. 2022 May 26;20(1):31. doi: 10.1186/s12959-022-00389-9.

Authors

Lisette Warkentin^#¹, Susann Hueber^#², Barthold Deiters³, Florian Klohn³, Thomas Kühlein²

Affiliations

¹ Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of General Practice, Universitätsklinikum Erlangen, Universitätsstraße, Erlangen, Germany. lisette.warkentin@uk-erlangen.de.
² Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of General Practice, Universitätsklinikum Erlangen, Universitätsstraße, Erlangen, Germany.
³ GWQ ServicePlus AG, Gesellschaft für Wirtschaftlichkeit und Qualität bei Krankenkassen, Tersteegenstraße, Düsseldorf, Germany.

^# Contributed equally.

Abstract

Background: For stroke prevention in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been increasingly prescribed instead of vitamin-K-antagonists (VKA). For some patients a lower dosage of DOACs (ld-DOACs) is recommended. Ld-DOAC prescribing seems to be common, although previous studies did not show clear superiority of ld-DOACs over warfarin. In Germany, phenprocoumon is used almost exclusively as VKA. Randomized controlled trials comparing DOACs and phenprocoumon in the general population of patients with AF do not exist. Therefore, we aimed to compare ld-DOACs and phenprocoumon in a real-world setting in Germany.

Methods: In a retrospective observational cohort study, claims data from a group of small to medium-sized health insurance companies were analysed. Risks for the outcomes thromboembolism, death and major bleeding were estimated by Cox regression. Out of 93,685 patients with atrial fibrillation and a first prescription of an oral anticoagulant, 20,179 receiving VKA and 21,724 ld-DOACs (29.6% of all DOAC patients) were included. For the sensitivity analysis phenprocoumon was compared to the five ld-DOAC groups (ld-apixaban, ld-dabigatran, ld-edoxaban, ld-rivaroxaban, and the composite of all ld-DOACs) after propensity-score matching.

Results: Phenprocoumon was associated with statistically significant fewer thromboembolic events (HR = 1.29, 95% CI [1.13, 1.48], p < .001) and deaths (HR = 1.52, 95% CI [1.41, 1.63], p < .001) and a non-significant higher bleeding risk (HR = 0.89, 95% CI [0.79, 1.00], p = .051) than composite ld-DOAC. Regarding the subgroups, only patients with ld-apixaban had a statistically significant higher risk for thromboembolic events (HR = 1.42, 95% CI [1.21, 1.65], p < .001) and a lower bleeding risk (HR = 0.75, 95% CI [0.65, 0.86], p < .001). Ld-apixaban, ld-edoxaban, and ld-rivaroxaban were associated with a higher risk of death. The sensitivity analysis confirmed these associations.

Conclusion: Phenprocoumon seems to be superior to ld-DOACs for patients with AF. As a hypothesis phenprocoumon might turn out to be the wiser choice for high-risk patients with AF as compared to ld-DOACs, especially regarding thromboembolic events and death. Therefore, RCTs comparing ld-DOACs with phenprocoumon are needed.

Keywords: Atrial fibrillation; Direct oral anticoagulants; Low-dose therapy; Phenprocoumon; Vitamin-K-antagonists.