Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: A prospective study

Pharmacogenetics and Genomics

Volumn 19, Issue 10, 2009, Pages 800-812

  Jorgensen, Andrea L ^a   Al Zubiedi, Sameh ^a   Zhang, Jieying Eunice ^a   Keniry, Andrew ^c   Hanson, Anita ^a,b   Hughes, Dyfrig A ^d   Eker, Diane Van ^a,b   Stevens, Lisa ^a,b   Hawkins, Karen ^a,b   Toh, Cheng H ^a,b   Kamali, Farhad ^e   Daly, Ann K ^e   Fitzmaurice, David ^f   Coffey, Alison ^c   Williamson, Paula R ^a   Park, Brian Kevin ^a   Deloukas, Panos ^c   Pirmohamed, Munir ^a,b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST   (United Kingdom)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^d BANGOR UNIVERSITY   (United Kingdom)

^e NEWCASTLE UNIVERSITY   (United Kingdom)

^f UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Dosing algorithms; Haemorrhage; Pharmacogenetics; Variability; Warfarin

Indexed keywords

BLOOD CLOTTING FACTOR 5; CYTOCHROME P450 2C18; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A5; MEMBRANE PROTEIN; PROTEIN S; PROTEIN VKORC1; UNCLASSIFIED DRUG; WARFARIN;

ADULT; AGED; ANTICOAGULATION; ARTICLE; BLEEDING; CLINICAL TRIAL; CONTROLLED STUDY; DRUG COST; DRUG EFFICACY; ENVIRONMENTAL FACTOR; EPISTAXIS; FEMALE; FOLLOW UP; GENETIC VARIABILITY; HEART ATRIUM FIBRILLATION; HEMARTHROSIS; HEMATEMESIS; HEMATURIA; HEMOPTYSIS; HEREDITY; HUMAN; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MELENA; MUSCLE HEMATOMA; PRIORITY JOURNAL; SINGLE BLIND PROCEDURE; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT OUTCOME; TREATMENT RESPONSE; UNIVARIATE ANALYSIS;

ADULT; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP3A; ENVIRONMENT; FEMALE; GENETIC VARIATION; GENOTYPE; HUMANS; MALE; MIDDLE AGED; MIXED FUNCTION OXYGENASES; TREATMENT OUTCOME; WARFARIN;

EID: 70349571987     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e3283317ab5     Document Type: Article

References (56)

1. Aguilar MI, Hart R, Pearce LA. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2007; 3:CD006186.
2. Fanikos J, Grasso-Correnti N, Shah R, Kucher N, Goldhaber SZ. Major bleeding complications in a specialized anticoagulation service. Am J Cardiol 2005; 96:595-598.
3. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J 2007; 7:99-111.
4. D'Andrea G, D'Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005; 105:645-649.
5. Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353:717-719.
6. Zhu Y, Shennan M, Reynolds KK, Johnson NA, Herrnberger MR, Valdes R Jr, Linder MW. Estimation of warfarin maintenance dose based on VKORC1 (-1639 G> A) and CYP2C9 genotypes. Clin Chem 2007; 53:1199-1205.
7. Millican EA, Lenzini PA, Milligan PE, Grosso L, Eby C, Deych E, et al. Genetic-based dosing in orthopedic patients beginning warfarin therapy. Blood 2007; 110:1511-1515.
8. Gage B, Eby C, Johnson J, Deych E, Rieder M, Ridker P, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008; 84:326-331.
9. Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005; 14:1745-1751.
10. Vecsler M, Loebstein R, Almog S, Kurnik D, Goldman B, Halkin H, Gak E. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb Haemost 2006; 95:205-211.
11. Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005; 106:2329-2333.
12. Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 2005; 352:2285-2293.
13. Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, et al. Interindividual variability in sensitivity to warfarin-Nature or nurture? Clin Pharmacol Ther 2001; 70:159-164.
14. Lee SC, Ng SS, Oldenburg J, Chong PY, Rost S, Guo JY, et al. Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population. Clin Pharmacol Ther 2006; 79:197-205.
15. Wadelius M, Sorlin K, Wallerman O, Karlsson J, Yue QY, Magnusson PK, et al. Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J 2004; 4:40-48.
16. Wu AHB, Wang P, Smith A, Haller C, Drake K, Linder M, Valdes R. Dosing algorithm for warfarin using CYP2C9 and VKORC1 genotyping from a multiethnic population: comparison with other equations. Pharmacogenomics 2008; 9:169-178.
17. Herman D, Peternel P, Stegnar M, Breskvar K, Dolzan V. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemost 2006; 95:782-787.
18. Caldwell MD, Berg RL, Zhang KQ, Glurich I, Schmelzer JR, Yale SH, et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res 2007; 5:8-16.
19. Kuehn BM. Warfarin label update. JAMA 2007; 298:1389.
20. Bussey HI, Wittkowsky AK, Hylek EM, Walker MB. Genetic testing for warfarin dosing? Not yet ready for prime time. Pharmacotherapy 2008; 28:141-143.
21. Garcia DA. Warfarin and pharmacogenomic testing: the case for restraint. Clin Pharmacol Ther 2008; 84:303-305.
22. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S-198S.
23. Hughes DA, Pirmohamed M. Warfarin pharmacogenetics: economic considerations. Pharmacoeconomics 2007; 25:899-902.
24. Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, et al. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther 2008; 83:312-321.
25. Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 2008; 358:999-1008.
26. Wadelius M, Chen LY, Lindh JD, Eriksson N, Ghori MJ, Bumpstead S, et al. The largest prospective warfarin-treated cohort supports genetic forecasting. Blood 2008; 113:784-792.
27. Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics. Ann Intern Med 1996; 124:970-979.
28. Wadelius M, Chen LY, Downes K, Ghori J, Hunt S, Eriksson N, et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J 2005; 5:262-270.
29. Wadelius M, Chen LY, Eriksson N, Bumpstead S, Ghori J, Wadelius C, et al. Association of warfarin dose with genes involved in its action and metabolism. Hum Genet 2007; 121:23-34.
30. British National Formulary. www.bnf.org. (September 2007) Edition 54.
31. Carlquist JF, Horne BD, Muhlestein JB, Lappe DL, Whiting BM, Kolek MJ, et al. Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study. J Thromb Thrombol 2006; 22:191-197.
32. Aquilante CL, Langaee TY, Lopez LM, Yarandi HN, Tromberg JS, Mohuczy D, et al. Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clin Pharmacol Ther 2006; 79:291-302.
33. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B (Methodological) 1995; 57:289-300.
34. Curtis L, Netten A. Unit costs of health and social care 2006. Canterbury: Personal Social Services Research Unit, University of Kent; 2006.
35. Manning WG, Mullahy J. Estimating log models: to transform or not to transform? J Health Econ 2001; 20:461-494.
36. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120:897-902.
37. Fennerty A, Dolben J, Thomas P, Backhouse G, Bentley DP, Campbell IA, Routledge PA. Flexible induction dose regimen for warfarin and prediction of maintenance dose. BMJ (Clinical Research Ed) 1984; 288:1268-1270.
38. Fergusson RJ, Eade OE, Logie AW, Gaddie J. A flexible loading dose schedule for warfarin therapy. Scott Med J 1987; 32:169-171.
39. Cosh DG, Moritz CK, Ashman KJ, Dally RJ, Gallus AS. Prospective evaluation of a flexible protocol for starting treatment with warfarin and predicting its maintenance dose. Aust N Z J Med 1989; 19:191-197.
40. Sawyer WT, Poe TE, Canaday BR, Weiner JS, Williams DM, Webb CE, Ellison MJ. Multicenter evaluation of six methods for predicting warfarin maintenance-dose requirements from initial response. Clin Pharmacy 1985; 4:440-446.
41. Limdi NA, Beasley TM, Crowley MR, Goldstein JA, Rieder MJ, Flockhart DA, et al. VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. Pharmacogenomics 2008; 9:1445-1458.
42. Meckley LM, Wittkowsky AK, Rieder MJ, Rettie AE, Veenstra DL. An analysis of the relative effects of VKORC1 and CYP2C9 variants on anticoagulation related outcomes in warfarin-treated patients. Thromb Haemost 2008; 100:229-239.
43. Takeuchi F, McGinnis R, Bourgeois S, Barnes C, Eriksson N, Soranzo N, et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 2009; 5:e1000433.
44. Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115:2689-2696.
45. Kristensen SR. Warfarin treatment of a patient with coagulation factor IX propeptide mutation causing warfarin hypersensitivity. Blood 2002; 100:2676-2677.
46. Van der Heijden JF, Rekke B, Hutten BA, van der Meer FJ, Remkes MG, Vermeulen M, et al. Non-fatal major bleeding during treatment with vitamin K antagonists: influence of soluble thrombomodulin and mutations in the propeptide of coagulation factor IX. J Thromb Haemost 2004; 2:1104-1109.
47. Au N, Rettie AE. Pharmacogenomics of 4-hydroxycoumarin anticoagulants. Drug Metab Rev 2008; 40:355-375.
48. Gak E, Halkin H. Shifting paradigms in the pharmacogenetics of warfarin. Pharmacogenomics 2008; 9:1373-1375.
49. Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360:753-764.
50. Caraco Y, Blotnick S, Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther 2008; 83:460-470.
51. Anderson JL, Horne BD, Stevens SM, Grove AS, Barton S, Nicholas ZP, et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation 2007; 116:2563-2570.
52. Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D, Song F. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling. Health Technol Assess 2007; 11:iii-iv
53. Hallinen T, Martikainen JA, Soini EJ, Suominen L, Aronkyto T. Direct costs of warfarin treatment among patients with atrial fibrillation in a Finnish health care setting. Curr Med Res Opin 2006; 22:683-692.
54. Raftery J. Costing in economic evaluation. BMJ 2000; 320:1597.
55. Jowett S, Bryan S, Mahe I, Brieger D, Carlsson J, Kartman B, Nevinson M. A multinational investigation of time and traveling costs in attending anticoagulation clinics. Value Health 2008; 11:207-212.
56. Cooper GM, Johnson JA, Langaee TY, Feng H, Stanaway IB, Schwarz UI, et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood 2008; 112:1022-1027.