Cost‐Effectiveness of Pharmacogenetics‐Guided Warfarin Therapy vs. Alternative Anticoagulation in Atrial Fibrillation

Pharmacogenetics‐guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics‐guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost‐effectiveness of anticoagulation treatment options. A clinical trial simulation of S‐warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta‐analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost‐effective options. Along the cost‐effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics‐guided warfarin and apixaban had incremental cost‐effectiveness ratios of £13,226 and £20,671 per quality‐adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost‐effective treatment.

[1]  R. Beyth,et al.  Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[2]  Mark A. Crowther,et al.  The Pharmacology and Management of the Vitamin K Antagonists , 2004 .

[3]  J. Plumb,et al.  Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? , 2008, Journal of thrombosis and haemostasis : JTH.

[4]  P. Deloukas,et al.  A Pharmacometric Model Describing the Relationship Between Warfarin Dose and INR Response With Respect to Variations in CYP2C9, VKORC1, and Age , 2010, Clinical pharmacology and therapeutics.

[5]  D. Atar,et al.  Apixaban versus warfarin in patients with atrial fibrillation. , 2011, The New England journal of medicine.

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

[7]  M. Gold Effect of Home Testing of International Normalized Ratio on Clinical Events , 2011 .

[8]  Jörgen Möller,et al.  Discrete event simulation: the preferred technique for health economic evaluations? , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

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

[10]  T. Walley,et al.  Economic Evaluations During Early (Phase II) Drug Development , 2012, PharmacoEconomics.

[11]  Munir Pirmohamed,et al.  Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses , 2011, BMJ : British Medical Journal.

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

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

[14]  S. Wilson Methods for the economic evaluation of health care programmes , 1987 .

[15]  M. Sculpher,et al.  Representing uncertainty: the role of cost-effectiveness acceptability curves. , 2001, Health economics.

[16]  R L Berg,et al.  Integration of Genetic, Clinical, and INR Data to Refine Warfarin Dosing , 2010, Clinical pharmacology and therapeutics.

[17]  M. Cowie National Institute for Health and Care Excellence. , 2015, European heart journal.

[18]  M. Pirmohamed,et al.  Comparative effectiveness of dabigatran, rivaroxaban, apixaban and warfarin in the management of patients with non-valvular atrial fibrillation , 2013, Clinical pharmacology and therapeutics.

[19]  H. Champion,et al.  Economic considerations. , 1993, Critical care clinics.

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

[21]  G. Cheng,et al.  Potential Clinical and Economic Outcomes of CYP2C9 and VKORC1 Genotype‐Guided Dosing in Patients Starting Warfarin Therapy , 2009, Clinical pharmacology and therapeutics.

[22]  K. Fahrbach,et al.  Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis. , 2004, Chest.

[23]  H G Watson,et al.  Guidelines on oral anticoagulation (warfarin): third edition – 2005 update , 2006, British journal of haematology.

[24]  Mark Crowther,et al.  Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[25]  R. Troughton,et al.  Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. , 2011, The New England journal of medicine.

[26]  Paolo Vicini,et al.  Pharmacogenomic trial design: use of a PK/PD model to explore warfarin dosing interventions through clinical trial simulation , 2009, Pharmacogenetics and genomics.

[27]  Panos Deloukas,et al.  The largest prospective warfarin-treated cohort supports genetic forecasting. , 2009, Blood.

[28]  N. Geller,et al.  Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial , 2010, Clinical trials.

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

[30]  M. Pirmohamed,et al.  Influence of CYP2C9 and VKORC1 on Patient Response to Warfarin: A Systematic Review and Meta-Analysis , 2012, PloS one.

[31]  A. Localio,et al.  Risk factors for nonadherence to warfarin: results from the IN‐RANGE study , 2008, Pharmacoepidemiology and drug safety.

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

[33]  J. You,et al.  Cost-Effectiveness of Dabigatran versus Genotype-Guided Management of Warfarin Therapy for Stroke Prevention in Patients with Atrial Fibrillation , 2012, PloS one.

[34]  F R Rosendaal,et al.  A Method to Determine the Optimal Intensity of Oral Anticoagulant Therapy , 1993, Thrombosis and Haemostasis.

[35]  S. Yusuf,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[36]  Kate M. O'Dell,et al.  New oral anticoagulants for atrial fibrillation: a review of clinical trials. , 2012, Clinical therapeutics.

[37]  B. Horne,et al.  A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) , 2012, Circulation.