Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

Tim A.C. de Vries; Imaad U. Mallick; Vinai C. Bhagirath; John W. Eikelboom; Calvin Gomes; Qilong Yi; Sean McGrath; Jack Hirsh; Noel C. Chan

doi:10.1055/a-2446-1348

Thrombosis and Haemostasis, Table of Contents

CC BY 4.0 · Thromb Haemost 2025; 125(06): 563-573
DOI: 10.1055/a-2446-1348

Stroke, Systemic or Venous Thromboembolism

Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

Authors

Tim A.C. de Vries ^*

¹Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

²Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands

³Department of Cardiology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands

⁴Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands
Imaad U. Mallick ^*

⁵School of Medicine, St. George's University, Grenada, West Indies

⁶Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada
Vinai C. Bhagirath

⁶Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada

⁷Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

⁸Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
John W. Eikelboom

⁶Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada

⁷Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

⁸Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
Calvin Gomes

⁹School of Medicine, Poznan University of Medical Sciences, Poznan, Poland
Qilong Yi

¹⁰School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
Sean McGrath

¹¹Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States
Jack Hirsh

⁷Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Noel C. Chan

⁶Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada

⁷Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

⁸Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

Abstract

Background

Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations.

Methods

This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF. We used random effects models and the quantile estimation method to estimate the median and a usual on-therapy range (10^th and 90^th percentiles).

Results

Of 4,822 unique publications, 53 studies met eligibility (29,266 trough and 12,103 peak levels). Usual on-therapy ranges for trough levels were 38 to 155 and 58 to 206 ng/mL for apixaban 2.5 and 5 mg twice daily; 35 to 138 and 33 to 151 ng/mL for dabigatran 110 and 150 mg twice daily; 8 to 54 and 13 to 66 ng/mL for edoxaban 30 and 60 mg daily; and 16 to 74 and 19 to 72 ng/mL for rivaroxaban 15 and 20 mg daily. The corresponding range for peak levels were 96 to 251 and 132 to 343; 65 to 223 and 76 to 285; 57 to 219 and 127 to 407; 131 to 384, and 169 to 313 ng/mL, respectively.

Conclusion

This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.

Keywords

direct oral anticoagulant - blood coagulation tests - drug monitoring - biological variation - population - factor Xa inhibitors - anticoagulants - hemorrhage

Full Text

References

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