PMID- 29498009
OWN - NLM
STAT- MEDLINE
DCOM- 20181106
LR  - 20220330
IS  - 1179-1942 (Electronic)
IS  - 0114-5916 (Linking)
VI  - 41
IP  - 7
DP  - 2018 Jul
TI  - Using the Symmetry Analysis Design to Screen for Adverse Effects of Non-vitamin K 
      Antagonist Oral Anticoagulants.
PG  - 685-695
LID - 10.1007/s40264-018-0650-6 [doi]
AB  - INTRODUCTION: Knowledge on adverse effects (AEs) related to non-vitamin K 
      antagonist oral anticoagulants (NOACs) in real-world populations is sparse. 
      OBJECTIVE: Our objective was to identify signals of potential AEs in patients 
      with atrial fibrillation (AF) initiating NOAC treatment using a hypothesis-free 
      screening approach. METHODS: Using the nationwide Danish registries, we 
      identified patients with AF initiating dabigatran, rivaroxaban, or apixaban 
      between 2011 and 2015 (n = 50,627). Applying a symmetry analysis design, we 
      screened for AEs of NOAC, as reflected by new drug treatments, incident 
      diagnoses, or procedures. For signals with the lowest number needed for one 
      additional patient to be harmed (NNTH), we evaluated whether they likely 
      represented genuine AEs or other types of associations. Signals assessed as 
      potential AEs were grouped into five categories for analysis of effect 
      modification according to patient and drug characteristics. RESULTS: Of the 
      identified signals, 61 were classified as potential AEs. Most signals could be 
      categorized as the following types of AEs: bleedings, non-bleeding 
      gastrointestinal symptoms, mental disease, urinary tract disorders, and 
      musculoskeletal symptoms. Older age and first-ever use of anticoagulants was 
      associated with strengthening of all "NOAC-adverse effect" associations. 
      Conversely, use of low-dose NOAC and apixaban led to attenuation of most 
      associations. CONCLUSION: Through a symmetry analysis-based hypothesis-free 
      screening of large-scale healthcare databases, we were able to confirm 
      well-established AEs of NOAC therapy in clinical practice as well as potential 
      AEs that deserve further investigation.
FAU - Hellfritzsch, Maja
AU  - Hellfritzsch M
AD  - Clinical Pharmacology and Pharmacy, Department of Public Health, University of 
      Southern Denmark, J.B. Winslows Vej 19, 2, 5000, Odense C, Denmark. 
      mmhellfritzsch@health.sdu.dk.
FAU - Rasmussen, Lotte
AU  - Rasmussen L
AD  - Clinical Pharmacology and Pharmacy, Department of Public Health, University of 
      Southern Denmark, J.B. Winslows Vej 19, 2, 5000, Odense C, Denmark.
FAU - Hallas, Jesper
AU  - Hallas J
AD  - Clinical Pharmacology and Pharmacy, Department of Public Health, University of 
      Southern Denmark, J.B. Winslows Vej 19, 2, 5000, Odense C, Denmark.
FAU - Pottegard, Anton
AU  - Pottegard A
AD  - Clinical Pharmacology and Pharmacy, Department of Public Health, University of 
      Southern Denmark, J.B. Winslows Vej 19, 2, 5000, Odense C, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
RN  - 0 (Anticoagulants)
RN  - 12001-79-5 (Vitamin K)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticoagulants/*administration & dosage/*adverse effects
MH  - Denmark/epidemiology
MH  - Drug-Related Side Effects and Adverse Reactions/*diagnosis/*epidemiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Registries
MH  - *Vitamin K
EDAT- 2018/03/03 06:00
MHDA- 2018/11/07 06:00
CRDT- 2018/03/03 06:00
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2018/11/07 06:00 [medline]
PHST- 2018/03/03 06:00 [entrez]
AID - 10.1007/s40264-018-0650-6 [pii]
AID - 10.1007/s40264-018-0650-6 [doi]
PST - ppublish
SO  - Drug Saf. 2018 Jul;41(7):685-695. doi: 10.1007/s40264-018-0650-6.