Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.
Administration, Oral
Aged
Aged, 80 and over
Antithrombins
/ administration & dosage
Atrial Fibrillation
/ diagnosis
Dabigatran
/ administration & dosage
Databases, Factual
Factor Xa Inhibitors
/ administration & dosage
Female
Hemorrhage
/ chemically induced
Humans
Male
Medicare
Off-Label Use
Practice Patterns, Physicians'
Retrospective Studies
Risk Assessment
Risk Factors
Rivaroxaban
/ administration & dosage
Stroke
/ diagnosis
Thromboembolism
/ diagnosis
Time Factors
Treatment Outcome
United States
/ epidemiology
Atrial fibrillation
Bleeding
Direct oral anticoagulants
Stroke
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
03 02 2020
03 02 2020
Historique:
received:
22
05
2019
accepted:
13
01
2020
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
21
10
2020
Statut:
epublish
Résumé
We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk. We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > =65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose. We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3 months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR = 1.44; 95% CI 1.14-1.8, P = 0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P = 0.002) and gastrointestinal bleeding (Dabigatran: HR = 1.48; 95% CI 1.08-2, P = 0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR = 0.59; 95% CI 0.43-0.8, P < 0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P = 0.03) and intracranial bleeding (Dabigatran: HR = 0.33; 95% CI 0.12-0.9, P = 0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban. While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.
Sections du résumé
BACKGROUND
We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk.
METHODS
We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > =65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose.
RESULTS
We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3 months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR = 1.44; 95% CI 1.14-1.8, P = 0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P = 0.002) and gastrointestinal bleeding (Dabigatran: HR = 1.48; 95% CI 1.08-2, P = 0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR = 0.59; 95% CI 0.43-0.8, P < 0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P = 0.03) and intracranial bleeding (Dabigatran: HR = 0.33; 95% CI 0.12-0.9, P = 0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban.
CONCLUSIONS
While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.
Identifiants
pubmed: 32013886
doi: 10.1186/s12872-020-01340-4
pii: 10.1186/s12872-020-01340-4
pmc: PMC6998084
doi:
Substances chimiques
Antithrombins
0
Factor Xa Inhibitors
0
Rivaroxaban
9NDF7JZ4M3
Dabigatran
I0VM4M70GC
Types de publication
Comparative Study
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
42Subventions
Organisme : NIA NIH HHS
ID : R01 AG055663
Pays : United States
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