Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants

Coordinator of START2-Register, Sophie Testa, Cristina Legnani, Emilia Antonucci, Oriana Paoletti, Claudia Dellanoce, Benilde Cosmi, Vittorio Pengo, Daniela Poli, Rossella Morandini, Roberto Testa, Armando Tripodi, Gualtiero Palareti

Research output: Contribution to journalArticlepeer-review


Essentials Currently, DOACs are given at fixed doses and do not require laboratory monitoring. Direct oral anticoagulant-specific measurements were performed at trough and peak. Patients who developed bleeding events showed higher DOAC plasma levels at peak. This study suggests the need of a more accurate DOAC dose assessment. Background: Direct oral anticoagulants (DOACs) are administered at fixed dose. The aim of the study was to evaluate the relationship between DOAC C-trough or C-peak plasma levels and bleeding complications in patients with non-valvular atrial fibrillation (NVAF). Methods: Five hundred sixty five consecutive naive NVAF patients were enrolled. The DOAC measurements at C-trough and at C-peak (available in 411 patients) were performed at steady state, within the first month of treatment. Major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and minor bleeding (MinB), occurring during 1 year of follow-up after blood sampling, were recorded. For each DOAC, interval of C-trough and C-peak levels was subdivided into four equal classes and results were attributed to these classes; the median values of results were also calculated. Results: Two hundred eight patients were on apixaban, 185 on dabigatran, and 172 on rivaroxaban. For 1-[qqqdeletezzz] year follow up for all patients, we observed: 19 MB (3.36%), 6 CRNMB (1.06%), and 47 MinB (8.31%). The prevalence of bleeding patients with anticoagulant levels in the upper classes of C-peak activity (II + III + IV) was higher than that in the lowest class. Normalized results of C-peak levels were higher in patients with bleeding than in those without bleeding. Conclusions: Bleeding complications during DOAC treatment were more frequent among atrial fibrillation (AF) patients with higher C-peak anticoagulant levels. In addition to a previous study that showed an increased risk of thrombotic complications in the patients with low C-trough levels, this study seems to indicate that patients with NVAF on DOACs would need a more accurate definition of their optimal therapeutic window.

Original languageEnglish
Pages (from-to)1064-1072
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - Jan 1 2019


  • atrial fibrillation
  • bleeds
  • direct oral anticoagulant
  • level
  • peak

ASJC Scopus subject areas

  • Hematology


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