Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement

Sorrel E. Wolowacz; Neil S. Roskell; Jonathan M. Plumb; Andreas Clemens; Herbert Noack; Paul A. Robinson; Gerry Dolan; Ivan J. Brenkel

doi:10.1160/TH09-08-0579

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(02): 360-371
DOI: 10.1160/TH09-08-0579

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement

Sorrel E. Wolowacz

¹RTI Health Solutions, Manchester, UK

,

Neil S. Roskell

¹RTI Health Solutions, Manchester, UK

,

Jonathan M. Plumb

²Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany

,

Andreas Clemens

²Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany

,

Herbert Noack

²Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany

,

Paul A. Robinson

³Boehringer Ingelheim Ltd, Bracknell, UK

,

Gerry Dolan

⁴Department of Haematology, Queen‘s Medical Centre, University Hospital, Nottingham, UK

,

Ivan J. Brenkel

⁵Department of Orthopaedic Surgery, Fife Acute Hospitals NHS Trust, Queen Margaret Hospital, Dunfermline, UK

› Author Affiliations

Abstract

Summary

Oral dabigatran etexilate is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement or total hip replacement. We investigated the cost-effectiveness of the 150 mg once daily (od) dose recommended for patients aged over 75 or with moderate renal impairment, from a United Kingdom National Health Service perspective. Dabigatran etexilate was compared with subcutaneous enoxaparin 40 mg od, using a decision model. Risks for VTE and bleeding were derived from subgroup analyses of the phase III trials. Dabigatran etexilate was less costly than enoxaparin; cost savings varied from £62 to £274 (base-case analyses) and were primarily due to differences in administration costs. Results were robust across a range of sensitivity analyses. Dabigatran etexilate 150 mg od is cost saving compared with enoxaparin 40 mg od in patients aged over 75 years and in patients with moderate renal impairment, with comparable efficacy and safety.

Keywords

Thromboembolism - primary prevention - total hip replacement - total knee replacement - economics

Full Text

References

References
1 The Royal College of Surgeons in England.. Publications. National Collaborating Centre for Acute Care. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. April 2007. Available at: http://www.rcseng.ac.uk/pub lications/docs/venous_thrombo.html/?searchterm=guideline. Accessed September 30, 2008.
2 Davidson BL, Sullivan SD, Kahn SR. et al. The economics of venous thromboembolism prophylaxis: a primer for clinicians. Chest 2003; 124 (Suppl. 06) 393S-6S.5.
3 National Institute for Health and Clinical Excellence.. Clinical guidelines CG46 Venous thromboembolism (surgical). Available at: www.nice.org.uk/CG046. Accessed September 30, 2008.
4 Warwick D, Friedman RJ, Agnelli G. et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg 2007; 89: 799-807.
5 Busby LT, Weyman A, Rodgers GM. Excessive anticoagulation in patients with mild renal insufficiency receiving long-term therapeutic enoxaparin. Am J Hematol 2001; 67: 54-56.
6 Thorevska N, Amoateng-Adjepong Y, Sabahi R. et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004; 125: 856-863.
7 Family Practice Notebook.. Creatinine clearance. Available at: www.fpnotebook.com/Renal/Lab/CrtnClrnc.htm. Accessed March 11, 2009.
8 Arixtra 2.5mg/0.5ml solution for injection, pre-filled syringe.. Summary of product characteristics. Available at: http://emc.medicines.org.uk/medicine 15123/SPC/Arixtra+2.5mg+0.5ml+solution+for+injection%2c+pre-filled+syringe. Accessed March 11, 2009.
9 Pradaxa 110 mg hard capsules.. Summary of product characteristics. Available at: http://emc.medicines.org.uk/medicine/20760/SPC/Pradaxa+110+mg+hard + capsules. Accessed March 11, 2009.
10 Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008; 47: 285-295.
11 Eriksson BI, Dahl OE, Rosencher N. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 5: 2178-2185.
12 Ginsberg JS, Davidson BL, Comp PC. et al. The oral thrombin inhibitor dabigatran etexilate vs the North American enoxaparin regimen for the prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24: 1-9.
13 Eriksson BI, Dahl OE, Rosencher N. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370: 949-956.
14 Wolowacz SE, Roskell NS, Maciver F. et al. Economic analysis of dabigatran etexilate for the prevention of venous thromboembolism following total knee and hip replacement surgery. Clin Ther 2009; 31: 1-19.
15 National Institute for Health and Clinical Excellence.. Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. Technology appraisal guidance 157. Available at: http://www.nice.org.uk nicemedia/pdf/TA157Guidance.pdf. Accessed March 11, 2009.
16 Scottish Medicines Consortium.. Dabigatran etexilate, 75mg and 110mg hard capsules (Pradaxa). No. 466/08. Available at: http://www.scottishmedicines.org.uk smc/files/dabigatran%20etexilate%20Pradaxa%20FINAL%20May%202008% 20for%20website.pdf. Accessed March 11, 2009.
17 Dahl OE, Kurth AA, Rosencher N. et al. Efficacy and safety profile of dabigatran etexilate for the prevention of venous thromboembolism in moderately renally impaired patients after total knee or hip replacement surgery. Blood. 2008 112: 361 (Abstract 981).
18 Dahl OE, Kurth AA, Rosencher N. et al. Efficacy and safety profile of dabigatran etexilate compared with enoxaparin in primary venous thromboembolism prevention after total knee or hip replacement surgery in patients over 75 years. Blood 2008; 112: 167 (Abstract 437).
19 Clexane pre-filled syringes and multi-dose vial.. Summary of product characteristics. Available at: http://emc.medicines.org.uk/medicine/12847/SPC/Clex ane+Pre-Filled+Syringes+and+Multi-dose+Vial/. Accessed March 11, 2009.
20 Department of Health.. NHS reference costs 2005–06. Available at: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_062884. Accessed September 30, 2008.
21 Joint Formulary Committee.. British National Formulary. Edition 57. London, British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
22 Offord R, Lloyd AC, Anderson P, Bearne A. Economic evaluation of enoxaparin for the prevention of venous thromboembolism in acutely ill medical patients. Pharm World Sci 2004; 26: 214-220.
23 Personal Social Services Research Unit. Curtis L. Unit costs of health and social care, 2007. Available at: http://www.pssru.ac.uk/uc/uc2007contents.htm. Accessed September 30, 2008.
24 Watts AC, Howie CR, Simpson AH. Assessment of a self-administration protocol for extended subcutaneous thromboprophylaxis in lower limb arthroplasty. J Bone Joint Surg 2006; 88-B: 107-110.
25 Committee for Medicinal Products for Human Use.. Guideline on clinical investigation of medicinal products for prophylaxis of high intra- and postoperative venous thromboembolic risk, 15 November 2007. http://www.emea.europa.eu pdfs/human/ewp/70798en_fin.pdf. Accessed February 23, 2009.
26 Menzin J, Colditz GA, Regan MM. et al. Cost-effectiveness of enoxaparin vs low-dose warfarin in the prevention of deep-vein thrombosis after total hip replacement surgery. Arch Intern Med 1995; 155: 757-764.
27 Oster G, Tuden RL, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. J Am Med Assoc 1987; 257: 203-208.
28 Gordois A, Posnett J, Borris L. et al. The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery. J Thromb Haemost 2003; 1: 2167-2174.
29 White RH, Romano PS, Zhou H. et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525-1531.
30 e-medicine. Lieberskind DS. Intracranial hemorrhage. Available at: www.emedicine.com/neuro/topic177.htm. Accessed May 23, 2007.
31 Muntz J, Scott DA, Lloyd A. et al. Major bleeding rates after prophylaxis against venous thromboembolism: systematic review, meta-analysis, and cost implications. Int J Technol Assess Health Care 2004; 20: 405-414.
32 Dubinsky I, Penello DR. Can specific patient variables be used to predict outcome of intracranial hemorrhage?. Am J Emerg Med 2002; 20: 26-29.
33 Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 2005; 106: 2710-2715.
34 Almeida JI, Coats R, Liem TK. et al. Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome. J Vasc Surg 1998; 27: 309-314.
35 National Joint Registry for England and Wales. Drury P, Morrison J, Newell C. et al. Fourth annual clinical report: 2006 data. Available at: http://www.njrcentre. org.uk/NjrCentre/LinkClick.aspx?fileticket=8ym2zOoRfvw%3d&tabid= 86&mid=523. Accessed September 30, 2008.
36 Office for National Statistics, UK Statistics Authority.. Deaths: age and sex, numbers and rates, 1976 onwards (England and Wales); population trends 128. Available at: http://www.statistics.gov.uk/STATBASE/Expodata/Spreadsheets D9552.xls. Accessed September 30, 2008.
37 Briggs A. Probabilistic analysis of cost-effectiveness models: statistical representation of parameter uncertainty. Value Health 2005; 8: 1-2.
38 National Institute for Health and Clinical Excellence.. Guide to the methods of technology appraisal (reference N0515). 2004. Available at: http://www.nice.org. uk/page.aspx?o=201974. Accessed September 30, 2008.
39 Wolowacz SE, Roskell NS, Plumb JM. et al. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty: a meta-analysis. Thromb Haemost 2009; 101: 77-85.
40 Wolowacz SE, Hess N, Brennan VK. et al. Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee replacement surgery: the evolving application of health economic modelling over 20 years. Curr Med Res Opin 2008; 24: 2993-3006.
41 Hull RD, Yusen RD, Bergqvist D. State-of-the-art review: Assessing the safety profiles of new anticoagulants for major orthopedic surgery thromboprophylaxis. Clin Appl Thromb Hemost 2009; 15: 377-388.
42 Burnett RS, Clohisy JC, Wright RW. et al. Failure of the American College of Chest Physicians-1A protocol for Lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 2007; 22: 317-324.