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Laboratory Monitoring of Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial FibrillationA Review

Educational Objective
To understand the role of monitoring of anticoagulant effects of novel oral anticoagulants (NOACs) in the setting of atrial fibrillation.
1 Credit CME
Abstract

Importance  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.

Observations  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.

Conclusions and Relevance  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.

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Article Information

Accepted for Publication: January 27, 2017.

Corresponding Author: Daniel J. Quinlan, MBBS, Department of Radiology, King’s College Hospital, Denmark Hill, London SE5 9RS, England (dan.quinlan@nhs.net).

Published Online: March 29, 2017. doi:10.1001/jamacardio.2017.0364

Author Contributions: Drs Eikelboom and Quinlan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: Eikelboom, Quinlan, Hirsh.

Drafting of the manuscript: Eikelboom, Quinlan, Weitz.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: All authors.

Study supervision: Eikelboom, Quinlan.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Eikelboom reported receiving honoraria and research support from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Janssen Pharmaceuticals, and Daiichi Sankyo. Dr Quinlan reported serving as a consultant to and receiving honoraria from Bayer, Boehringer Ingelheim, and Sanofi. Dr Connolly reported receiving honoraria and research support from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, and Janssen Pharmaceuticals. Dr Weitz reported serving as a consultant to and receiving honoraria from Boehringer Ingelheim, Bayer, Janssen Pharmaceuticals, Johnson & Johnson, Bristol-Myers Squibb, Pfizer, Daiichi Sankyo, Portola, and Ionis Pharmaceuticals. No other disclosures were reported.

Funding/Support: Dr Eikelboom is the recipient of a Mid-Career Award from the Heart and Stroke Foundation of Canada. Dr Weitz holds the Canada Research Chair (Tier I) in Thrombosis and the Heart and Stroke Foundation of Canada J. F. Mustard Chair in Cardiovascular Research.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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