{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:44:52Z","timestamp":1791945892054,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe temporal trends in the clinical landscape of vitamin K antagonist (VKA) treatment in the Netherlands, after the introduction of a lower international normalized ratio (INR) target range in 2016 and direct oral anticoagulants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 17 Dutch anticoagulation clinics between 2014 and 2022 were individually linked to nationwide healthcare data. Prevalent VKA users were identified on January 1 of each year, forming nine annual cohorts. We assessed baseline patient characteristics, anticoagulation treatment quality (using time in\/above\/below therapeutic range [TTR\/ATR\/BTR]), and annual odds ratios of major bleeding and thromboembolism for each cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The number of patients treated with VKAs increased from 101\u2009090 in 2014 to 121\u2009916 in 2017, followed by a decline to 73\u2009649 in 2022. Over time, cohorts were characterized by increasing age and a higher prevalence of comorbidities, with a doubling of kidney disease. After the introduction of the lower INR target range, mean BTR decreased (~30% in 2014 to ~15% in 2022), while mean TTR increased (~54% in 2014 to ~67% in 2022), with stable mean ATR. Across calendar years, the 1\u2010year odds ratio of major bleeding decreased from 1.71% (95% CI 1.63\u20131.79) in 2014 to 1.52% (95% CI 1.44\u20131.61) in 2022, whereas the odds ratio of ischemic stroke\/transient ischemic attack\/systemic thromboembolism increased from 1.14% (95% CI 1.08\u20131.21) in 2014 to 1.32% (95% CI 1.24\u20131.40) in 2022. The 1\u2010year odds ratio of mortality increased from 5.09 (95% CI 4.95\u20135.22) to 8.55 (95% CI 8.35\u20138.75), with an OR of 1.74 (95% CI 1.68\u20131.81).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VKA users declined between 2014 and 2022. The remaining patients using VKA became older and more comorbid. During this period, INR target ranges were lowered, while temporal changes were observed with decreasing odds ratio of major bleeding and increasing odds ratio of thromboembolism and mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70494","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:45:38Z","timestamp":1791780338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal Trends in Patient Characteristics, Anticoagulation Treatment Quality, and Clinical Outcomes of Individuals Receiving Vitamin K Antagonists in the Netherlands (2014 Until\u20132022)"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-4055","authenticated-orcid":false,"given":"Gilda D.","family":"Zielinski","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-0007","authenticated-orcid":false,"given":"Qingui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Critical Care Medicine, the First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J. H. A.","family":"Kruip","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Quality and Patient Care Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-0754","authenticated-orcid":false,"given":"Frederikus A.","family":"Klok","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thrombosis and Haemostasis Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-2303","authenticated-orcid":false,"given":"Suzanne C.","family":"Cannegieter","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Medicine, Thrombosis and Haemostasis Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-401X","authenticated-orcid":false,"given":"Nienke","family":"van Rein","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12959\u2010017\u20100156\u2010y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw658"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.9973"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(13)62343\u20100"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201004\u2010571232"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2287472"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae176"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001830"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.10.038"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066485"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf01061909"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15081"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12597"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20053825"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1651587"},{"key":"e_1_2_12_17_1","first-page":"a1724","article-title":"Het Effect Van Aanpassing Van de Therapeutische INR\u2010Range Op Het Optreden Van Bloedingen en Trombo\u2010Embolische Complicaties Bij Atriumfibrilleren","volume":"5","author":"Prins A.","year":"2020","journal-title":"Nederlands Platform Voor Farmaceutisch Onderzoek"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/23969873211062011"},{"issue":"9","key":"e_1_2_12_19_1","first-page":"546","article-title":"Evaluation of Vitamin K Antagonists Management and Control in Patients With Mechanical Prosthetic Heart Valves During the COVID\u201019 Pandemic","volume":"26","author":"Gilboa I.","year":"2024","journal-title":"Israel Medical Association Journal"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2024.101358"},{"key":"e_1_2_12_21_1","unstructured":"N.v.ReinandF. N. T.Jaarverslag \u201cFederatie Van Nederlandse Trombosediensten\u201d(2024)."},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/17474930211034331"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029613490828"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euaf238"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70494","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pds.70494","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:58:42Z","timestamp":1791943122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.70494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/pds.70494"],"URL":"https:\/\/doi.org\/10.1002\/pds.70494","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70494"}}