{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:40:45Z","timestamp":1784832045030,"version":"3.55.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"cross-disciplinary funding project of Henan University for young scholars"},{"name":"key research project for higher education in Henan Province"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>Warfarin has a narrow therapeutic window and large variability in dosing that are affected by clinical and genetic factors. To help guide the dosing of warfarin, the Clinical Pharmacogenetics Implementation Consortium has recommended the use of pharmacogenetic algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al. when genotype information is available.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study, simulations were performed in Chinese cohorts to explore how dosing differences between Western (by IWPC and Gage et al.) and Chinese algorithms (by Miao et al.) would mean in terms of anticoagulation effect in clinical trials. We first tried to replicate a published clinical trial comparing genotype-guided dosing to routine clinical dosing in Chinese patients. We then made simulations where Chinese cohorts received daily doses recommended by Gage, IWPC, and Miao algorithms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We found that in simulation conditions where dosing specifications were strictly followed, genotype-guided dosing by IWPC and Lenzini formulae was more likely to overshoot the upper limit of the therapeutic window by day 15, and thus may have a lower % time in therapeutic range (%TTR) than that of clinical dosing group. Also, in comparing Gage, IWPC, and Miao algorithms, we found that the Miao dosing cohort has the highest %TTR and the lowest risk of over-anticoagulation by day 28.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In summary, our results confirmed that algorithms developed based on data from local patients may be more suitable for achieving therapeutic international normalized ratio window in Chinese population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000545","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T14:21:45Z","timestamp":1726064505000},"page":"275-284","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Comparative performance of pharmacogenetics-based warfarin dosing algorithms in Chinese population: use of a pharmacokinetic\/pharmacodynamic model to explore dosing regimen through clinical trial simulation"],"prefix":"10.1097","volume":"34","author":[{"given":"Keli","family":"Shi","sequence":"first","affiliation":[{"name":"School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiexin","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Nursing and Health, Henan University, Kaifeng, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"R1-20250808","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1023\/A:1008833520158","article-title":"Initiation of warfarin therapy: recommendations and clinical pearls.","volume":"7","author":"Erban","year":"1999","journal-title":"J Thromb Thrombolysis"},{"key":"R2-20250808","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIR.0000000000001193","article-title":"2023 ACC\/AHA\/ACCP\/HRS Guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines.","volume":"149","author":"Joglar","year":"2024","journal-title":"Circulation"},{"key":"R3-20250808","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism.","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv"},{"key":"R4-20250808","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11239-007-0104-y","article-title":"Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues.","volume":"25","author":"Gage","year":"2008","journal-title":"J Thromb Thrombolysis"},{"key":"R5-20250808","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/sj.tpj.6500313","article-title":"Common VKORC1 and GGCX polymorphisms associated with warfarin dose.","volume":"5","author":"Wadelius","year":"2005","journal-title":"Pharmacogenomics J"},{"key":"R6-20250808","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(98)04474-2","article-title":"Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.","volume":"353","author":"Aithal","year":"1999","journal-title":"Lancet"},{"key":"R7-20250808","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1056\/NEJMoa0809329","article-title":"Estimation of the warfarin dose with clinical and pharmacogenetic data.","volume":"360","author":"Klein","year":"2009","journal-title":"N Engl J Med"},{"key":"R8-20250808","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/clpt.2008.10","article-title":"Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.","volume":"84","author":"Gage","year":"2008","journal-title":"Clin Pharmacol Ther"},{"key":"R9-20250808","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1056\/NEJMoa1311386","article-title":"A randomized trial of genotype-guided dosing of warfarin.","volume":"369","author":"Pirmohamed","year":"2013","journal-title":"N Engl J Med"},{"key":"R10-20250808","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1001\/jama.2017.11469","article-title":"Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: the GIFT randomized clinical trial.","volume":"318","author":"Gage","year":"2017","journal-title":"JAMA"},{"key":"R11-20250808","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1056\/NEJMoa1310669","article-title":"A pharmacogenetic versus a clinical algorithm for warfarin dosing.","volume":"369","author":"Kimmel","year":"2013","journal-title":"N Engl J Med"},{"key":"R12-20250808","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/clpt.2008.101","article-title":"Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.","volume":"84","author":"Schelleman","year":"2008","journal-title":"Clin Pharmacol Ther"},{"key":"R13-20250808","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1182\/blood-2009-12-255992","article-title":"Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups.","volume":"115","author":"Limdi","year":"2010","journal-title":"Blood"},{"key":"R14-20250808","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1253\/circj.71.761","article-title":"Incidence of major bleeding complication of warfarin therapy in Japanese patients with atrial fibrillation.","volume":"71","author":"Suzuki","year":"2007","journal-title":"Circ J"},{"key":"R15-20250808","first-page":"250","article-title":"[Low intensity anticoagulation therapy after mechanical heart valve replacement].","volume":"41","author":"Dong","year":"2003","journal-title":"Zhonghua Wai Ke Za Zhi"},{"key":"R16-20250808","doi-asserted-by":"crossref","first-page":"e94573","DOI":"10.1371\/journal.pone.0094573","article-title":"Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.","volume":"9","author":"Zhao","year":"2014","journal-title":"PLoS One"},{"key":"R17-20250808","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2217\/pgs-2019-0124","article-title":"Comparison of the prediction performance of different warfarin dosing algorithms based on Chinese patients.","volume":"21","author":"Xie","year":"2020","journal-title":"Pharmacogenomics"},{"key":"R18-20250808","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/jcph.2197","article-title":"Comparison of maintenance dose predictions by warfarin dosing algorithms based on Chinese and Western patients.","volume":"63","author":"Deng","year":"2023","journal-title":"J Clin Pharmacol"},{"key":"R19-20250808","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s00228-007-0381-6","article-title":"Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients.","volume":"63","author":"Miao","year":"2007","journal-title":"Eur J Clin Pharmacol"},{"key":"R20-20250808","doi-asserted-by":"crossref","first-page":"e002602","DOI":"10.1161\/CIRCGEN.119.002602","article-title":"Genotype-guided dosing of warfarin in Chinese adults: a multicenter randomized clinical trial.","volume":"13","author":"Guo","year":"2020","journal-title":"Circ Genom Precis Med"},{"key":"R21-20250808","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/clpt.2010.13","article-title":"Integration of genetic, clinical, and INR data to refine warfarin dosing.","volume":"87","author":"Lenzini","year":"2010","journal-title":"Clin Pharmacol Ther"},{"key":"R22-20250808","doi-asserted-by":"crossref","first-page":"e105891","DOI":"10.1371\/journal.pone.0105891","article-title":"Determinants of the over-anticoagulation response during warfarin initiation therapy in Asian patients based on population pharmacokinetic-pharmacodynamic analyses.","volume":"9","author":"Ohara","year":"2014","journal-title":"PLoS One"},{"key":"R23-20250808","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/cpt.2754","article-title":"Cost effectiveness of pharmacogenetic testing for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines: a systematic review.","volume":"112","author":"Morris","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"R24-20250808","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2147\/RMHP.S454463","article-title":"A China-based cost-effectiveness analysis of novel oral anticoagulants versus warfarin in patients with left ventricular thrombosis.","volume":"17","author":"Tian","year":"2024","journal-title":"Risk Manag Healthc Policy"},{"key":"R25-20250808","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/jcpt.13575","article-title":"Cost-effectiveness of anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation in mainland China.","volume":"47","author":"Zhou","year":"2022","journal-title":"J Clin Pharm Ther"},{"key":"R26-20250808","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1161\/CIR.0000000000000665","article-title":"2019 AHA\/ACC\/HRS Focused Update of the 2014 AHA\/ACC\/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons.","volume":"140","author":"January","year":"2019","journal-title":"Circulation"},{"key":"R27-20250808","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":"Hindricks","year":"2021","journal-title":"Eur Heart J"},{"key":"R28-20250808","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1056\/NEJMoa2209051","article-title":"Rivaroxaban in rheumatic heart disease-associated atrial fibrillation.","volume":"387","author":"Connolly","year":"2022","journal-title":"N Engl J Med"},{"key":"R29-20250808","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1161\/CIRCULATIONAHA.111.019737","article-title":"Using pharmacogenetics in real time to guide warfarin initiation: a clinician update.","volume":"124","author":"Carlquist","year":"2011","journal-title":"Circulation"},{"key":"R30-20250808","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41397-019-0083-3","article-title":"Precision dosing of warfarin: open questions and strategies.","volume":"19","author":"Li","year":"2019","journal-title":"Pharmacogenomics J"},{"key":"R31-20250808","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1111\/bcp.14608","article-title":"Warfarin dosing algorithms: a systematic review.","volume":"87","author":"Asiimwe","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"R32-20250808","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.2169\/internalmedicine.40.1183","article-title":"Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation.","volume":"40","author":"Yasaka","year":"2001","journal-title":"Intern Med"},{"key":"R33-20250808","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/j.1365-2125.2005.02361.x","article-title":"Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation?","volume":"59","author":"You","year":"2005","journal-title":"Br J Clin Pharmacol"},{"key":"R34-20250808","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s12013-011-9275-4","article-title":"Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses.","volume":"62","author":"Haibo","year":"2012","journal-title":"Cell Biochem Biophys"},{"key":"R35-20250808","doi-asserted-by":"crossref","first-page":"14846","DOI":"10.1038\/s41598-024-65048-7","article-title":"Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method.","volume":"14","author":"Xia","year":"2024","journal-title":"Sci Rep"},{"key":"R36-20250808","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/clpt.2010.37","article-title":"A pharmacometric model describing the relationship between warfarin dose and INR response with respect to variations in CYP2C9, VKORC1, and age.","volume":"87","author":"Hamberg","year":"2010","journal-title":"Clin Pharmacol Ther"}],"container-title":["Pharmacogenetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T12:01:17Z","timestamp":1754654477000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/fpc.0000000000000545","relation":{},"ISSN":["1744-6872","1744-6880"],"issn-type":[{"value":"1744-6872","type":"print"},{"value":"1744-6880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]}}}