Risk Profiles of New Users of Oral Anticoagulants Between 2011 and 2019 in Germany

Abstract

Purpose

Over the last decade, the use of direct oral anticoagulants (DOACs) has strongly increased. We aimed to describe and compare risk profiles including potential changes over time among persons with non-valvular atrial fibrillation initiating treatment with different DOACs or phenprocoumon (vitamin K antagonist) between 2011 and 2019 in Germany.

Patients and Methods

Using the German Pharmacoepidemiological Research Database (GePaRD; claims data of ~20% of the German population), we identified persons with a first dispensing of phenprocoumon or a DOAC and a diagnosis of non-valvular atrial fibrillation between August 2011 and December 2019. We described the morbidity of included patients prior to treatment initiation, stratified by year of treatment initiation.

Results

Overall, we included 448,028 new users (phenprocoumon: N = 118,117, rivaroxaban: N = 130,997, apixaban: N = 130,300, edoxaban: N = 38,128, dabigatran: N = 30,486). Comparing new DOAC users in 2019, the proportion with prior ischemic stroke was highest for dabigatran (17%) and lowest for rivaroxaban (8%). The proportion with prior major bleeding was also highest for dabigatran (25%) and lowest for edoxaban (20%). New users of apixaban were oldest and, eg, showed the highest prevalence of congestive heart failure. Changes over time were most pronounced for phenprocoumon. For example, among persons initiating phenprocoumon in 2012 vs 2019, the proportion with prior major bleeding increased from 18% to 35%; the proportion with renal disease increased from 20% to 36% and the proportion with liver disease from 18% to 24%.

Conclusion

This study demonstrated differences in risk profiles between new users of different oral anticoagulants and substantial changes over time among new phenprocoumon users. These differences have to be considered in head-to-head comparisons of these drugs based on observational data, especially regarding potential unmeasured confounding.

Keywords:

• atrial fibrillation
• oral anticoagulants
• direct oral anticoagulants
• DOACs
• risk profiles

Ethics

The utilization of health insurance data for scientific research in Germany is regulated by the Code of Social Law. All involved health insurance providers as well as the German Federal (Social) Insurance Office and the Senator for Science, Health, and Consumer Protection in Bremen as their responsible authorities approved the use of GePaRD data for this study. Informed consent for studies based on claims data is required by law unless obtaining consent appears unacceptable and would bias results, which was the case in this study. According to the Ethics Committee of the University of Bremen studies based on GePaRD are exempt from institutional review board review. We thus complied with relevant data and privacy regulations.

Acknowledgment

The authors would like to thank all statutory health insurance providers which provided data for this study, namely AOK Bremen/Bremerhaven, DAK-Gesundheit, Die Techniker (TK), and hkk Krankenkasse. The authors would also like to thank Anja Gabbert and Philipp Alexander Volkmar for their support.

Disclosure

BK and UH are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. AV, KP and UA were employees at BIPS at the time when the study was conducted. Unrelated to this study, BIPS occasionally conducts post-authorization safety studies (PASS) requested by health authorities which are financed by pharmaceutical industry and performed in line with the ENCePP Code of Conduct. The design and conduct of this study as well as the interpretation and publication are not influenced by the pharmaceutical industry. The authors report no other conflicts of interest in this work.