TY - JOUR
T1 - Intracranial Hemorrhage Following Anticoagulant Treatment in Denmark
T2 - Spontaneous Adverse Drug Reaction Reports Versus Real-World Data
AU - von Osmanski, Benedikte Irene
AU - Schelde, Astrid Blicher
AU - Jimenez-Solem, Espen
AU - Nyeland, Martin Erik
AU - Horwitz, Henrik
N1 - © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2022/4
Y1 - 2022/4
N2 - INTRODUCTION: In Denmark, physicians are legally obliged to report serious adverse drug reactions (ADRs), such as intracranial hemorrhage (ICH) following anticoagulant (AC) treatment, to the Danish Medicines Agency. We were therefore puzzled to discover a high number of reports concerning ICHs following treatment with the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin. This was surprising, as all DOACs have been found to be associated with a lower risk of ICH compared with warfarin in phase III randomized controlled trials.OBJECTIVES: The primary aim of the study was to estimate the level of underreporting of ICH as an ADR following treatment with warfarin, dabigatran, rivaroxaban, and apixaban.METHODS: This observational study covered a 5-year period (2014-2018). Using nationwide registries held by the Danish Health Data Authority, the number of users, exposure time in person-years, and related ICH events for each of the study drugs were estimated. Data on ADR-ICH reports were extracted from the interactive ADR overviews held by the Danish Medicines Agency.RESULTS: From 2014 to 2018, 97.0% of the identified warfarin-related ICH events were not reported as ADRs. For the DOACs, the level of underreporting ranged from 88.8 to 90.8%.CONCLUSION: We found a heavy and differentiated level of underreporting of ICH as an ADR following treatment with the four study drugs.
AB - INTRODUCTION: In Denmark, physicians are legally obliged to report serious adverse drug reactions (ADRs), such as intracranial hemorrhage (ICH) following anticoagulant (AC) treatment, to the Danish Medicines Agency. We were therefore puzzled to discover a high number of reports concerning ICHs following treatment with the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin. This was surprising, as all DOACs have been found to be associated with a lower risk of ICH compared with warfarin in phase III randomized controlled trials.OBJECTIVES: The primary aim of the study was to estimate the level of underreporting of ICH as an ADR following treatment with warfarin, dabigatran, rivaroxaban, and apixaban.METHODS: This observational study covered a 5-year period (2014-2018). Using nationwide registries held by the Danish Health Data Authority, the number of users, exposure time in person-years, and related ICH events for each of the study drugs were estimated. Data on ADR-ICH reports were extracted from the interactive ADR overviews held by the Danish Medicines Agency.RESULTS: From 2014 to 2018, 97.0% of the identified warfarin-related ICH events were not reported as ADRs. For the DOACs, the level of underreporting ranged from 88.8 to 90.8%.CONCLUSION: We found a heavy and differentiated level of underreporting of ICH as an ADR following treatment with the four study drugs.
KW - Anticoagulants
KW - Atrial Fibrillation/drug therapy
KW - Dabigatran/adverse effects
KW - Denmark/epidemiology
KW - Drug-Related Side Effects and Adverse Reactions/complications
KW - Humans
KW - Intracranial Hemorrhages/chemically induced
KW - Pyridones
KW - Rivaroxaban/adverse effects
KW - Warfarin
UR - http://www.scopus.com/inward/record.url?scp=85126772364&partnerID=8YFLogxK
U2 - 10.1007/s40264-022-01147-6
DO - 10.1007/s40264-022-01147-6
M3 - Journal article
C2 - 35305263
VL - 45
SP - 379
EP - 388
JO - Drug Safety
JF - Drug Safety
SN - 0114-5916
IS - 4
ER -