The COAG and EU-PACT trials: What is the clinical benefit of pharmacogenetic-guided coumarin dosing during therapy initiation?

Current Molecular Medicine

Volumn 14, Issue 7, 2014, Pages 841-848

  Baranova, E V ^a   Asselbergs, F W ^b,c,d   de Boer, A ^a   Maitland van der Zee, A H ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

^b UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^c ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES   (Netherlands)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Acenocoumarol; COAG; CYP2C9; EU PACT; Pharmacogenetics; Phenprocoumon; VKORC1; Warfarin

Indexed keywords

ACENOCOUMAROL; AMIODARONE; ANTICOAGULANT AGENT; COUMARIN DERIVATIVE; FLUINDOSTATIN; PHENPROCOUMON; WARFARIN; CYTOCHROME P450 2C9; VITAMIN K EPOXIDE REDUCTASE; VKORC1 PROTEIN, HUMAN; COUMARIN ANTICOAGULANT;

ALGORITHM; CLINICAL PRACTICE; CYTOCHROME P450 2C9 GENE; DEEP VEIN THROMBOSIS; GENE; GENETIC VARIABILITY; GENOTYPE; HEREDITY; HUMAN; INTERNATIONAL NORMALIZED RATIO; LUNG EMBOLISM; MAINTENANCE DRUG DOSE; META ANALYSIS (TOPIC); MOLECULAR MEDICINE; PHARMACOGENETIC DOSING ALGORITHM; PHARMACOGENETICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; VITAMIN K EPOXIDE REDUCTASE COMPLEX 1 GENE; CHEMISTRY; DOSE RESPONSE; GENETIC PREDISPOSITION; GENETICS; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOEMBOLISM; ANTICOAGULANT THERAPY; ARTICLE; CLINICALLY BASED DOSING ALGORITHM; DRUG RESPONSE; DRUG SAFETY; GENOTYPE GUIDED DOSING ALGORITHM; MEDICAL DECISION MAKING; MULTICENTER STUDY (TOPIC); OUTCOME ASSESSMENT; STUDY DESIGN;

COUMARINS; CYTOCHROME P-450 CYP2C9; DOSE-RESPONSE RELATIONSHIP, DRUG; GENETIC PREDISPOSITION TO DISEASE; HUMANS; PHARMACOGENETICS; POLYMORPHISM, SINGLE NUCLEOTIDE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; THROMBOEMBOLISM; VITAMIN K EPOXIDE REDUCTASES;

EID: 84906912656     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/1566524014666140811114906     Document Type: Review

References (57)

1. Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119: 8S-21S.
2. Jonas DE, Wines R. Pharmacogenomic testing and the prospect of individualized treatment. N C Med J 2013; 74(6): 485-93.
3. Johnson JA, Gong L, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther 2011; 90(4): 625-9.
4. Verhoef TI, Redekop WK, van Schie RM, et al. Costeffectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs. Pharmacogenomics 2012; 13(12): 1405-17.
5. Verhoef TI, Redekop WK, Daly AK, et al. Pharmacogeneticguided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. Br J Clin Pharmacol 2014; 77(4): 626-41.
6. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335(8): 540-6.
7. Anderson JL, Horne BD, Stevens SM, et al. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation 2012; 125(16): 1997-2005.
8. Oden A, Fahlen M, Hart RG. Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal. Thromb Res 2006; 117(5): 493-9.
9. Kimmel SE. Warfarin therapy: in need of improvement after all these years. Expert Opin Pharmacother 2008; 9(5): 677-86.
10. Rubboli A, Becattini C, Verheugt FW. Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy. World J Cardiol 2011; 3(11): 351-8.
11. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365(21): 2002-12.
12. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329(7456): 15-9.
13. McMahan DA, Smith DM, Carey MA, Zhou XH. Risk of major hemorrhage for outpatients treated with warfarin. J Gen Intern Med 1998; 13: 311-6.
14. Gomes T, Mamdani MM, Holbrook AM, et al. Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ 2013; 185(2): E121-7.
15. Schalekamp T, de Boer A. Pharmacogenetics of oral anticoagulant therapy. Curr Pharm Des 2010; 16 (2): 187-203.
16. Limdi NA, Arnett DK, Goldstein JA, et al. Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans. Pharmacogenomics 2008; 9(5): 511-26.
17. 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 (9154): 717-9.
18. Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 2005; 352(22): 2285-93.
19. D'Andrea G, D'Ambrosio RL, Di Perna P, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005; 105 (2): 645-9.
20. Rost S, Fregin A, Ivaskevicius V, et al. Mutations in VKORC1cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004; 427(6974): 537-41.
21. Harrington DJ, Gorska R, Wheeler R, et al. Pharmacodynamic resistance to warfarin is associated with nucleotide substitutions in VKORC1. J Thromb Haemost 2008; 6(10): 1663-70.
22. Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease--implications for personalized medicine. Pharmacol Rev 2013; 65(3): 987-1009.
23. Daly AK. Optimal dosing of warfarin and other coumarin anticoagulants: the role of genetic polymorphisms. Arch Toxicol 2013; 87(3): 407-20.
24. Lenzini P, Wadelius M, Kimmel S, et al. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther 2010; 87(5): 572-8.
25. Lefevre F, Goodman SN, Piper MA. Pharmacogenetic testing for warfarin dosing still awaits validation. J Am Coll Cardiol 2011; 57(6): 756; author reply-7.
26. McMillin GA, Melis R, Wilson A, et al. Gene-based warfarin dosing compared with standard of care practices in an orthopedic surgery population: a prospective, parallel cohort study. Ther Drug Monit 2010; 32: 338-45.
27. Lenzini PA, Grice GR, Milligan PE, et al. Laboratory and clinical outcomes of pharmacogenetic vs clinical protocols for warfarin initiation in orthopedic patients. J Thromb Haemost 2008; 6(10): 1655-62.
28. Epstein RS, Moyer TP, Aubert RE, et al. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol 2010; 55(25): 2804-12.
29. Wen MS, Lee M, Chen JJ, et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. Clin Pharmacol Ther 2008; 84(1): 83-9.
30. Thacker SM, Grice GR, Milligan PE, Gage BF. Dosing anticoagulant therapy with coumarin drugs: is genotyping clinically useful? Yes. J Thromb Haemost 2008; 6(9): 1445-9.
31. Hillman MA, Wilke RA, Yale SH, et al. A Prospective, Randomized Pilot Trial of Model-Based Warfarin Dose Initiation using CYP2C9 Genotype and Clinical Data. Clin Med Res 2005; 3(3): 137-45.
32. 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(3): 460-70.
33. Anderson JL, Horne BD, Stevens SM, et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation 2007; 116(22): 2563-70.
34. Bussey HI, Wittkowsky AK, Hylek EM, Walker MB. Genetic testing for warfarin dosing? Not yet ready for prime time. Pharmacotherapy 2008; 28(2): 141-3.
35. Eckman MH, Rosand J, Greenberg SM, Gage BF. Costeffectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation. Ann Intern Med 2009; 150(2): 73-83.
36. Kimmel SE, French B, Kasner SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med 2013; 369(24): 2283-93.
37. Pirmohamed M, Burnside G, Eriksson N, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med 2013; 369(24): 2294-303.
38. Verhoef TI, Ragia G, de Boer A, et al. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl J Med 2013; 369(24): 2304-12.
39. Burmester JK, Berg RL, Yale SH, et al. A randomized controlled trial of genotype-based Coumadin initiation. Genet Med 2011; 13(6): 509-18.
40. Kangelaris KN, Bent S, Nussbaum RL, Garcia DA, Tice JA. Genetic testing before anticoagulation? A systematic review of pharmacogenetic dosing of warfarin. J Gen Intern Med 2009; 24(5): 656-64.
41. Huang SW, Chen HS, Wang XQ, et al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients. Pharmacogenet Genomics 2009; 19(3): 226-34.
42. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008; 84(3): 326-31.
43. Avery PJ, Jorgensen A, Hamberg AK, et al. A proposal for an individualized pharmacogenetics-based warfarin initiation dose regimen for patients commencing anticoagulation therapy. Clin Pharmacol Ther 2011; 90(5): 701-6.
44. van Schie RM, Wessels JA, le Cessie S, et al. Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data. Eur Heart J 2011; 32(15): 1909-17.
45. Do EJ, Lenzini P, Eby CS, et al. Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design. Pharmacogenomics J 2012; 12(5): 417-24.
46. Warfarin Adverse Event Reduction For Adults Receiving Genetic Testing at Therapy INitiation (WARFARIN). Available at: http://clinicaltrials.gov/ct2/show/NCT01305148?term=warfari n&rank=1 [accessed March 13, 2014].
47. Carcas AJ, Borobia AM, Velasco M, et al. Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial. Trials 2012; 13: 239.
48. Turner RM, Pirmohamed M. Cardiovascular pharmacogenomics: expectations and practical benefits. Clin Pharmacol Ther 2014; 95(3): 281-93.
49. Pereira N. COAG and EU-PACT: The Pharmacogenetics of Warfarin Dosing. Available at: http://www.medscape.com/viewarticle/815304#1 [accessed March 7, 2014].
50. Zineh I, Pacanowski M, Woodcock J. Pharmacogenetics and coumarin dosing--recalibrating expectations. N Engl J Med 2013; 369(24): 2273-5.
51. Limdi NA, Wadelius M, Cavallari L, et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood 2010; 115(18): 3827-34.
52. Scott SA, Jaremko M, Lubitz SA, et al. CYP2C9*8 is prevalent among African-Americans: implications for pharmacogenetic dosing. Pharmacogenomics 2009; 10(8): 1243-55.
53. Cavallari LH, Langaee TY, Momary KM, et al. Genetic and clinical predictors of warfarin dose requirements in African Americans. Clin Pharmacol Ther 2010; 87(4): 459-64.
54. Furie B. Do pharmacogenetics have a role in the dosing of vitamin K antagonists? N Engl J Med 2013; 369(24): 2345-6.
55. Verhoef TI, Redekop WK, Hegazy H, et al. Long-term anticoagulant effects of CYP2C9 and VKORC1 genotypes in phenprocoumon users. J Thromb Haemost 2012; 10(12): 2610-2.
56. Cairns JA. Which oral anticoagulant for which atrial fibrillation patient: recent clinical trials and evidence-based choices. Can J Cardiol 2013; 29(10): 1165-72.
57. Pink J, Pirmohamed M, Lane S, Hughes DA. Costeffectiveness of pharmacogenetics-guided warfarin therapy vs alternative anticoagulation in atrial fibrillation. Clin Pharmacol Ther 2014; 95(2): 199-207.