title: Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin - a model-based study.
abstract: OBJECTIVE
  Dabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation.
  
  
  METHODS
  In a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups.
  
  
  RESULTS
  Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups.
  
  
  CONCLUSIONS
  Patients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin.
authors.affiliation: Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria ; Department of Anesthesiology, Perioperative and Pain Medicine, Boston University, Boston, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Edrich
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston University, Boston, MA, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Frendl
authors.affiliation: Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, Boston University, Boston, MA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Michaud
authors.affiliation: Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA.
authors.forename: Ioannis Ch
authors.initials: ICh
authors.lastname: Paschalidis
keywords: NONMEM; PKPD model; atrial fibrillation; electrophysiology