More early bleeds associated with high baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study

Blood Adv. 2024 Sep 24;8(18):4913-4923. doi: 10.1182/bloodadvances.2024013126.

Abstract

Treatment with direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is effective and safe. However, bleeding complications still occur. Whether DOAC level measurement may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" study, venous blood was collected 15-30 days after DOAC initiation in patients with AF who were then followed up for 1 year to record the occurrence of major and clinically relevant nonmajor bleeding. DOAC plasma levels were measured in 1 laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients (957 [57.7%] and 700 patients treated with standard and low-dose, respectively). Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (>0.50), whereas 35 events (2.69% pt/yrs) occurred in those with values in the 2 lower classes (≤0.50, P = .0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first 3 months of treatment. Overall, 19% of patients receiving low doses had standardized values in the highest class. More bleeding occurred in patients on low (4.3% pt/yrs) vs standard (2.2% pt/yrs; P = .0160) dose DOAC. Early measurement of DOAC levels in patients with AF identified many individuals with high levels despite the low doses use and had more bleeding risk during the first 3 months of treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / adverse effects
  • Anticoagulants* / therapeutic use
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / etiology
  • Humans
  • Male
  • Middle Aged

Substances

  • Anticoagulants
  • Factor Xa Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03803579