Effect of Enzyme-Inducing Antiseizure Medications on the Risk of Sub-Therapeutic Concentrations of Direct Oral Anticoagulants: A Retrospective Cohort Study.
Administration, Oral
Aged
Aged, 80 and over
Anticoagulants
/ therapeutic use
Anticonvulsants
/ adverse effects
Atrial Fibrillation
/ drug therapy
Drug Interactions
/ physiology
Enzyme Inhibitors
/ therapeutic use
Female
Humans
Male
Middle Aged
Pyrazoles
/ therapeutic use
Pyridones
/ therapeutic use
Retrospective Studies
Seizures
/ drug therapy
Stroke
/ chemically induced
Journal
CNS drugs
ISSN: 1179-1934
Titre abrégé: CNS Drugs
Pays: New Zealand
ID NLM: 9431220
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
accepted:
16
01
2021
pubmed:
18
2
2021
medline:
11
1
2022
entrez:
17
2
2021
Statut:
ppublish
Résumé
Stroke and thromboembolic events occurring among patients taking direct oral anticoagulants (DOACs) have been associated with low concentrations of DOACs. Enzyme-inducing antiseizure medications (EI-ASMs) are associated with enhanced cytochrome-P450-mediated metabolism and enhanced P-glycoprotein-mediated transport. The aim of this study was to evaluate the effect of concomitant EI-ASM use on DOAC peak concentrations in patients treated in clinical care. We performed a retrospective cohort study of patients treated with DOACs for atrial fibrillation and venous thromboembolic disease in an academic general hospital. In total, 307 patients treated with DOACs between August 2015 and January 2020 were reviewed. Clinical characteristics and peak DOAC plasma concentrations of patients co-treated with an EI-ASM were compared with those of patients not treated with an EI-ASM. An apixaban dose score (ADS) was defined to account for apixaban dosage and the number of apixaban dose-reduction criteria. In total, 177 peak DOAC plasma concentrations (including apixaban, rivaroxaban, and dabigatran) from 131 patients were measured, including 24 patients co-treated with an EI-ASM and 107 controls not treated with an EI-ASM. The proportion of patients with DOAC concentrations below the expected range was significantly higher among EI-ASM users than among patients not taking an EI-ASM (37.5 vs. 9.3%, respectively; p = 0.0004; odds ratio 5.82; 95% confidence interval [CI] 2.03-16.66). Most of these patients were treated with apixaban (85%); however, sensitivity analysis results were also significant (p = 0.031) for patients with non-apixaban DOACs. In patients co-treated with apixaban and an EI-ASM, median apixaban peak concentration was 106 ng/mL (interquartile range [IQR] 71-181) compared with 150 ng/mL (IQR 94-222) in controls (p = 0.019). In multivariable analysis, EI-ASM use was associated with 6.26-fold increased odds for apixaban concentration below the expected range (95% CI 2.19-17.90; p = 0.001). Apixaban concentrations were significantly associated with EI-ASM use, moderate enzyme inhibitor use, and ADS. Concurrent EI-ASM and DOAC use presents a possible risk for DOAC concentrations below the expected range. The clinical significance of the interaction is currently unclear.
Sections du résumé
BACKGROUND
Stroke and thromboembolic events occurring among patients taking direct oral anticoagulants (DOACs) have been associated with low concentrations of DOACs. Enzyme-inducing antiseizure medications (EI-ASMs) are associated with enhanced cytochrome-P450-mediated metabolism and enhanced P-glycoprotein-mediated transport.
OBJECTIVE
The aim of this study was to evaluate the effect of concomitant EI-ASM use on DOAC peak concentrations in patients treated in clinical care.
METHODS
We performed a retrospective cohort study of patients treated with DOACs for atrial fibrillation and venous thromboembolic disease in an academic general hospital. In total, 307 patients treated with DOACs between August 2015 and January 2020 were reviewed. Clinical characteristics and peak DOAC plasma concentrations of patients co-treated with an EI-ASM were compared with those of patients not treated with an EI-ASM. An apixaban dose score (ADS) was defined to account for apixaban dosage and the number of apixaban dose-reduction criteria.
RESULTS
In total, 177 peak DOAC plasma concentrations (including apixaban, rivaroxaban, and dabigatran) from 131 patients were measured, including 24 patients co-treated with an EI-ASM and 107 controls not treated with an EI-ASM. The proportion of patients with DOAC concentrations below the expected range was significantly higher among EI-ASM users than among patients not taking an EI-ASM (37.5 vs. 9.3%, respectively; p = 0.0004; odds ratio 5.82; 95% confidence interval [CI] 2.03-16.66). Most of these patients were treated with apixaban (85%); however, sensitivity analysis results were also significant (p = 0.031) for patients with non-apixaban DOACs. In patients co-treated with apixaban and an EI-ASM, median apixaban peak concentration was 106 ng/mL (interquartile range [IQR] 71-181) compared with 150 ng/mL (IQR 94-222) in controls (p = 0.019). In multivariable analysis, EI-ASM use was associated with 6.26-fold increased odds for apixaban concentration below the expected range (95% CI 2.19-17.90; p = 0.001). Apixaban concentrations were significantly associated with EI-ASM use, moderate enzyme inhibitor use, and ADS.
CONCLUSIONS
Concurrent EI-ASM and DOAC use presents a possible risk for DOAC concentrations below the expected range. The clinical significance of the interaction is currently unclear.
Identifiants
pubmed: 33595834
doi: 10.1007/s40263-021-00795-z
pii: 10.1007/s40263-021-00795-z
pmc: PMC8332574
doi:
Substances chimiques
Anticoagulants
0
Anticonvulsants
0
Enzyme Inhibitors
0
Pyrazoles
0
Pyridones
0
apixaban
3Z9Y7UWC1J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
305-316Commentaires et corrections
Type : ErratumIn
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