{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:52:41Z","timestamp":1790200361547,"version":"4.1.0"},"reference-count":75,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart and Stroke of Canada New Investigator Award"},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"crossref","award":["DGE2140743"],"award-info":[{"award-number":["DGE2140743"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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 (10th and 90th percentiles).<\/jats:p>\n                  <jats:p>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\u2009ng\/mL for apixaban 2.5 and 5\u2009mg twice daily; 35 to 138 and 33 to 151\u2009ng\/mL for dabigatran 110 and 150\u2009mg twice daily; 8 to 54 and 13 to 66\u2009ng\/mL for edoxaban 30 and 60\u2009mg daily; and 16 to 74 and 19 to 72\u2009ng\/mL for rivaroxaban 15 and 20\u2009mg 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\u2009ng\/mL, respectively.<\/jats:p>\n                  <jats:p>This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.<\/jats:p>","DOI":"10.1055\/a-2446-1348","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T21:05:26Z","timestamp":1732223126000},"page":"563-573","source":"Crossref","is-referenced-by-count":6,"title":["Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis"],"prefix":"10.1055","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1392-8193","authenticated-orcid":false,"given":"Tim A.C.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands"},{"name":"Department of Cardiology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5829-0348","authenticated-orcid":false,"given":"Imaad U.","family":"Mallick","sequence":"additional","affiliation":[{"name":"School of Medicine, St. George's University, Grenada, West Indies"},{"name":"Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinai C.","family":"Bhagirath","sequence":"additional","affiliation":[{"name":"Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada"},{"name":"Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada"},{"name":"Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Gomes","sequence":"additional","affiliation":[{"name":"School of Medicine, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7281-3516","authenticated-orcid":false,"given":"Sean","family":"McGrath","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Hirsh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-6172","authenticated-orcid":false,"given":"Noel C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Hematology and Thromboembolism, Department of Medicine, Population Health Research Institute, Hamilton, Ontario, Canada"},{"name":"Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1055\/s-0042-1760330","article-title":"Clinical studies with anticoagulants that have changed clinical practice","volume":"49","author":"J Hirsh","year":"2023","journal-title":"Semin Thromb Hemost"},{"issue":"05","key":"ref2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"G Hindricks","year":"2021","journal-title":"Eur Heart J"},{"issue":"10","key":"ref3","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1093\/europace\/euab065","article-title":"2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation","volume":"23","author":"J Steffel","year":"2021","journal-title":"Europace"},{"issue":"9921","key":"ref4","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials","volume":"383","author":"C T Ruff","year":"2014","journal-title":"Lancet"},{"issue":"08","key":"ref5","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1055\/a-1450-8178","article-title":"2021 Update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants","volume":"121","author":"J Douxfils","year":"2021","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1055\/s-0041-1740492","article-title":"Can a single measurement of apixaban levels identify patients at risk of overexposure? 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