Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants

Cardiovasc Drugs Ther. 2018 Dec;32(6):591-600. doi: 10.1007/s10557-018-6825-7.

Abstract

Purpose: This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF).

Methods: We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events.

Results: Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02-1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48-1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events.

Conclusions: The number and duration of potential DDIs and patients' comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.

Keywords: Atrial fibrillation; Bleeding; Drug-drug interactions; Non-vitamin K oral anticoagulants; Switching.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Databases, Factual
  • Drug Interactions
  • Drug Substitution*
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Polypharmacy
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*
  • Young Adult

Substances

  • Anticoagulants
  • Vitamin K
  • Warfarin