title: Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation: A Review.
abstract: The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy.
  
  
  
  The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven.
  
  
  
  Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada2Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada3Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada4Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: Department of Radiology, King's College Hospital, London, England.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Quinlan
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada3Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada4Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada3Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada4Hamilton Health Sciences, Hamilton, Ontario, Canada6Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000097:blood / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D000069604:Dabigatran / Q000097:blood / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000097:blood / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011720:Pyrazoles / Q000097:blood / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000627:therapeutic use; D011728:Pyridones / Q000097:blood / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000097:blood / Q000627:therapeutic use; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000097:blood / Q000627:therapeutic use; D013918:Thrombin Time; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban