The Comparison of Inappropriate-Low-Doses Use among 4 Direct Oral Anticoagulants in Patients with Atrial Fibrillation: From the Database of a Single-Center Registry

J Stroke Cerebrovasc Dis. 2018 Nov;27(11):3280-3288. doi: 10.1016/j.jstrokecerebrovasdis.2018.07.028. Epub 2018 Aug 16.

Abstract

Background: Inappropriate doses of direct oral anticoagulants (DOACs) are often prescribed. This study evaluated the prevalence, outcomes, and predictors of the prescription of inappropriately low doses of 4 types of DOACs in patients with atrial fibrillation (AF).

Methods: We retrospectively analyzed prospectively collected data from a single-center registry with 2272 patients prescribed DOACs for AF (apixaban: 1014; edoxaban: 267; rivaroxaban: 498; dabigatran: 493). Patients were monitored for 2years and classified into appropriate-dose (n = 1,753; including appropriate low doses), inappropriate-low-dose (n = 490) and inappropriate-high-dose groups (n = 29). Major bleeding (MB) and thromboembolic events (TEEs) were evaluated.

Results: The mean age was 72 ± 10years. The CHADS2 and HAS-BLED scores were 1.95 ± 1.32 and 1.89 ± .96, respectively. Overall, the incidences of MB and TEE were 2.3 and 2.1 per 100-patinet year, respectively. The inappropriate-low-dose group had younger age, heavier body weight, and higher creatinine clearance value than the appropriate-dose group. Multiple logistic regression analyses demonstrated the following independent determinants of the prescription of an inappropriately low dose: apixaban: HAS-BLED score; edoxaban: age; rivaroxaban: age, creatinine clearance value, HAS-BLED score, CHADS2 score, and antiplatelet therapy; dabigatran: age. There were not significant differences in the incidence of major bleeding and stroke/systemic emboli among the inappropriate-low-dose group of 4 DOACs compared with the appropriate-dose group of 4 DOACs.

Conclusions: In a single-center registry, 23% of patients with AF treated with a DOAC received an inappropriate dose. Several clinical factors, such as age and the creatinine clearance value, can identify patients at risk of under-treatment with DOACs.

Keywords: Direct oral anticoagulant; atrial fibrillation; major bleeding; stroke; systemic embolism.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Blood Coagulation / drug effects*
  • Chi-Square Distribution
  • Dabigatran / administration & dosage
  • Databases, Factual
  • Drug Dosage Calculations
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Inappropriate Prescribing*
  • Incidence
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Prevalence
  • Pyrazoles / administration & dosage
  • Pyridines / administration & dosage
  • Pyridones / administration & dosage
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Rivaroxaban / administration & dosage
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / epidemiology
  • Stroke / prevention & control*
  • Thiazoles / administration & dosage
  • Thromboembolism / blood
  • Thromboembolism / diagnosis
  • Thromboembolism / epidemiology
  • Thromboembolism / prevention & control*
  • Time Factors
  • Treatment Outcome

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridines
  • Pyridones
  • Thiazoles
  • apixaban
  • Rivaroxaban
  • Dabigatran
  • edoxaban