Warfarin Pharmacogenomics in Diverse Populations

Genotype‐guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin‐related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype‐guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race‐specific or admixture‐based algorithms may facilitate improved genotype‐guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype‐guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene–drug pairs and development of clinical recommendations for pharmacogenetic testing.

[1]  P. Laissue,et al.  Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients , 2018, Pharmacogenomics and personalized medicine.

[2]  T E Klein,et al.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics‐Guided Warfarin Dosing: 2017 Update , 2017, Clinical pharmacology and therapeutics.

[3]  S. Fullerton,et al.  Genomics is failing on diversity , 2016, Nature.

[4]  B. Gage,et al.  A systematic analysis and comparison of warfarin initiation strategies , 2016, Pharmacogenetics and genomics.

[5]  M. Perera,et al.  Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms , 2016, The Pharmacogenomics Journal.

[6]  Hui-juan Shi,et al.  Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese , 2016, European Journal of Clinical Pharmacology.

[7]  Hongtao Song,et al.  Verification of five pharmacogenomics-based warfarin administration models , 2016, Indian journal of pharmacology.

[8]  Kevin L. Thomas,et al.  Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: Insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry. , 2016, American heart journal.

[9]  J. Ge,et al.  Clinical application of a new warfarin-dosing regimen based on the CYP2C9 and VKORC1 genotypes in atrial fibrillation patients. , 2016, Biomedical reports.

[10]  J. Choi,et al.  Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients , 2016, Yonsei medical journal.

[11]  S. Vegter,et al.  Economic Evaluations of Pharmacogenetic and Pharmacogenomic Screening Tests: A Systematic Review. Second Update of the Literature , 2016, PloS one.

[12]  Cunegundo M Vergara,et al.  A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics , 2016, PloS one.

[13]  Sameh Alzubiedi,et al.  Pharmacogenetic-guided Warfarin Dosing Algorithm in African-Americans , 2016, Journal of cardiovascular pharmacology.

[14]  Z. Goldberger,et al.  National Trends in Ambulatory Oral Anticoagulant Use. , 2015, The American journal of medicine.

[15]  Scott M. Williams,et al.  Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin. , 2015, Chest.

[16]  Hong-Hao Zhou,et al.  Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database , 2015, PloS one.

[17]  J. You Universal versus genotype-guided use of direct oral anticoagulants in atrial fibrillation patients: a decision analysis. , 2015, Pharmacogenomics.

[18]  Elvin T. Price Warfarin pharmacogenomics and African ancestry. , 2015, Blood.

[19]  N. Limdi,et al.  Race influences warfarin dose changes associated with genetic factors. , 2015, Blood.

[20]  D. Nickerson,et al.  Variation in genes controlling warfarin disposition and response in American Indian and Alaska Native people: CYP2C9, VKORC1, CYP4F2, CYP4F11, GGCX , 2015, Pharmacogenetics and genomics.

[21]  J. Krieger,et al.  Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration. , 2015, Pharmacogenomics.

[22]  R. Kittles,et al.  Poor warfarin dose prediction with pharmacogenetic algorithms that exclude genotypes important for African Americans , 2015, Pharmacogenetics and genomics.

[23]  Nicole Soranzo,et al.  A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose , 2009, PLoS genetics.

[24]  Fang Luo,et al.  A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients , 2014, PloS one.

[25]  Li Zhao,et al.  Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement , 2014, PloS one.

[26]  Munir Pirmohamed,et al.  A Randomized Trial of Genotype-Guided Dosing of Warfarin , 2014 .

[27]  William K Redekop,et al.  Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. , 2014, British journal of clinical pharmacology.

[28]  Joshua C Denny,et al.  Using systems approaches to address challenges for clinical implementation of pharmacogenomics , 2014, Wiley interdisciplinary reviews. Systems biology and medicine.

[29]  J. Johnson,et al.  Warfarin Pharmacogenetics: An Illustration of the Importance of Studies in Minority Populations , 2014, Clinical pharmacology and therapeutics.

[30]  Sameh Alzubiedi,et al.  Dosage Individualization of Warfarin Using Artificial Neural Networks , 2014, Molecular Diagnosis & Therapy.

[31]  M Pirmohamed,et al.  Cost‐Effectiveness of Pharmacogenetics‐Guided Warfarin Therapy vs. Alternative Anticoagulation in Atrial Fibrillation , 2014, Clinical pharmacology and therapeutics.

[32]  Luis Ángel Bermúdez Bosch A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy , 2014, Journal of pharmacogenomics & pharmacoproteomics.

[33]  R. Califf,et al.  A pharmacogenetic versus a clinical algorithm for warfarin dosing. , 2013, The New England journal of medicine.

[34]  Rita Barallon,et al.  A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. , 2013, The New England journal of medicine.

[35]  J N Douglas,et al.  Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans , 2013, The Pharmacogenomics Journal.

[36]  Yusuke Nakamura,et al.  Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study , 2013, The Lancet.

[37]  M. R. Botton,et al.  Pharmacogenomics of warfarin in populations of African descent , 2013, British journal of clinical pharmacology.

[38]  Adam Bress,et al.  Effect of NQO1 and CYP4F2 genotypes on warfarin dose requirements in Hispanic-Americans and African-Americans. , 2012, Pharmacogenomics.

[39]  Cunegundo M Vergara,et al.  Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients. , 2012, Pharmacogenomics.

[40]  H. Zhou,et al.  Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement. , 2012, Die Pharmazie.

[41]  L. Cavallari,et al.  The future of warfarin pharmacogenetics in under-represented minority groups. , 2012, Future cardiology.

[42]  Heping Zhou,et al.  Accuracy assessment of pharmacogenetic algorithms for warfarin dose prediction in Chinese patients , 2012, American journal of hematology.

[43]  D. Hu,et al.  Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients , 2012, Journal of Thrombosis and Thrombolysis.

[44]  Melissa A. Basford,et al.  Predicting warfarin dosage in European-Americans and African-Americans using DNA samples linked to an electronic health record. , 2012, Pharmacogenomics.

[45]  Jason C. Fish,et al.  Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. , 2012, Chest.

[46]  Panos Deloukas,et al.  Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans , 2012, Pharmacogenetics and genomics.

[47]  C. Richards,et al.  Emergency hospitalizations for adverse drug events in older Americans. , 2011, The New England journal of medicine.

[48]  Soo-Youn Lee,et al.  Development and comparison of a warfarin-dosing algorithm for Korean patients with atrial fibrillation. , 2011, Clinical therapeutics.

[49]  M. R. Botton,et al.  Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry. , 2011, British journal of clinical pharmacology.

[50]  D. Nicolae,et al.  The Missing Association: Sequencing‐Based Discovery of Novel SNPs in VKORC1 and CYP2C9 That Affect Warfarin Dose in African Americans , 2011, Clinical pharmacology and therapeutics.

[51]  Edith Nutescu,et al.  Pharmacogenomics of warfarin dose requirements in Hispanics. , 2011, Blood cells, molecules & diseases.

[52]  J. You,et al.  Pharmacoeconomic evaluation of warfarin pharmacogenomics , 2011, Expert opinion on pharmacotherapy.

[53]  Yusuke Nakamura,et al.  Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese. , 2010, Human molecular genetics.

[54]  Elena Deych,et al.  Gamma-glutamyl carboxylase and its influence on warfarin dose , 2010, Thrombosis and Haemostasis.

[55]  Munir Pirmohamed,et al.  Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. , 2010, Blood.

[56]  P. Ridker,et al.  A Polymorphism in the VKORC1 Regulator Calumenin Predicts Higher Warfarin Dose Requirements in African Americans , 2010, Clinical pharmacology and therapeutics.

[57]  Marc S. Williams,et al.  A Policy Model to Evaluate the Benefits, Risks and Costs of Warfarin Pharmacogenomic Testing , 2010, PharmacoEconomics (Auckland).

[58]  M. Pirmohamed,et al.  Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design. , 2009, Pharmacogenomics.

[59]  Jerry Avorn,et al.  Cost-Effectiveness of Genotype-Guided Warfarin Dosing for Patients With Atrial Fibrillation , 2009, Circulation. Cardiovascular quality and outcomes.

[60]  J. Corral,et al.  Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy. , 2009, Blood.

[61]  R. Altman,et al.  Estimation of the warfarin dose with clinical and pharmacogenetic data. , 2009, The New England journal of medicine.

[62]  B. Gage,et al.  Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation , 2009, Annals of Internal Medicine.

[63]  E. Dias-Neto,et al.  Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients , 2008, Clinical pharmacology and therapeutics.

[64]  S. Yusuf,et al.  Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range , 2008, Circulation.

[65]  M. Rieder,et al.  Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin , 2008, Clinical pharmacology and therapeutics.

[66]  Larisa H Cavallari,et al.  Factors influencing warfarin dose requirements in African-Americans. , 2007, Pharmacogenomics.

[67]  Wansu Chen,et al.  Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. , 2007, Journal of the American College of Cardiology.

[68]  Susan Regan,et al.  Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation , 2007, Circulation.

[69]  M. Pirmohamed,et al.  Pharmacogenetics of warfarin: current status and future challenges , 2007, The Pharmacogenomics Journal.

[70]  Gregory W Albers,et al.  Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. , 2007, Archives of internal medicine.

[71]  P. Deloukas,et al.  Association of warfarin dose with genes involved in its action and metabolism , 2006, Human Genetics.

[72]  J. Hambleton,et al.  The Influence of Ethnicity on Warfarin Dosage Requirement , 2005, The Annals of pharmacotherapy.

[73]  V. Stone,et al.  Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[74]  H. Halkin,et al.  Interindividual variability in sensitivity to warfarin‐Nature or nurture? , 2001, Clinical pharmacology and therapeutics.

[75]  M. Turakhia,et al.  Racial Differences in Quality of Anticoagulation Therapy for Atrial Fibrillation (from the TREAT-AF Study). , 2016, The American journal of cardiology.

[76]  Julie A. Johnson,et al.  Warfarin pharmacogenetics. , 2015, Trends in cardiovascular medicine.

[77]  D. Krishna Kumar,et al.  Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population , 2013, European Journal of Clinical Pharmacology.

[78]  M. Whirl‐Carrillo,et al.  Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing , 2011, Clinical pharmacology and therapeutics.

[79]  Gordon H. Guyatt,et al.  Evidence-Based Management of Anticoagulant Therapy Antithrombotic Therapy and Prevention of Thrombosis , 2011 .