COST- EFFECTIVENESS OF INTENSIVE LIPID LOWERING THERAPY WITH 80 MG OF ATORVASTATIN, VERSUS 10 MG OF ATORVASTATIN, FOR SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE IN CANADA
Main Article Content
Keywords
Cardiovascular disease, atorvastatin, Markov model, cost-effectiveness, Canada
Abstract
Background
The TNT study compared high dose atorvastatin (80 mg) versus moderate atorvastatin (10 mg) treatment in 10,001 patients with stable coronary heart disease (CHD), over 4.9 years. Intensive lipid-lowering with atorvastatin (80 mg) reduced major cardiovascular events by 22%.
Objectives
To assess the cost-effectiveness of intensive lipid-lowering versus moderate lipid lowering treatment from the perspective of the Canadian Ministries of Health.
Methods
A lifetime Markov model was developed to predict cardiovascular (CV) events, costs, survival, and quality-adjusted life years (QALYs) for CHD patients receiving 80 mg versus 10 mg of atorvastatin. Predictions were also made for 10- and 5-year horizons. Treatment-specific event risks were used until five years. Beyond year five, equivalent CV risks were assumed for all patients. Medical-care costs and post-event survival were estimated using Canadian data. Health utility scores were obtained from published studies. Benefits and costs were discounted 5% annually. Probabilistic and deterministic sensitivity analyses were performed.
Results
Treatment with atorvastatin (80 mg) over a lifetime horizon resulted in increased costs (Can$16,542 vs. Can$15,365), survival (10.12 vs. 10.03 life years), and QALYs (7.71 vs. 7.61) per patient compared with atorvastatin (10 mg), yielding an incremental cost-effectiveness of Can$12,946 per life year gained and Can$11,969 per QALY. The incremental cost per QALY remained below Can$50,000 in 98.1% of 1000 simulations. Results were robust to variations in event hazard ratios, costs, health utility values, and discount rate.
Conclusion
Intensive atorvastatin (80 mg) treatment is predicted to be cost-effective versus atorvastatin (10 mg) for CHD patients in Canada.
References
1. Statistics Canada. Causes of death - Chapter XI: Diseases of the circulatory system. (April 27, 2007). 2007. http://www.statcan.ca/english/freepub/84-208- XIE/2007001/tbl-en.htm#9. (Accessed 17 Jul 2007).
2. Heart and Stroke Foundation of Canada, Health Canada, Canadian Cardiovascular Society. Centre for Chronic Disease Prevention and Control HC, Canadian Cardiovascular Society, Heart and Stroke Foundation of Canada, editors. The Growing Burden of Heart Disease and Stroke in Canada 2003. 2003.
3. Manuel DG, Leung M, Nguyen K, Tanuseputro P, Johansen H. Burden of cardiovascular disease in Canada. Can J Cardiol 2003;19(9):997-1004.
4. Choi BK, Pak AW. A method for comparing and combining cost-of-illness studies: an example from cardiovascular disease. Chronic Dis Can 2002;23(2):47-57.
5. Health Canada. Economic burden of illness in Canada, 1998. 1998. http://www.phacaspc.gc.ca/publicat/ebic-femc98/index.html.
6. Alter DA, Stukel TA, Newman A. Proliferation of cardiac technology in Canada: a challenge to the sustainability of Medicare. Circulation 2006;113(3):380-7.
7. Genest J, Frohlich J, Fodor G, McPherson R. Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. CMAJ 2003;169(9):921-4.
8. Gould AL, Davies GM, Alemao E, Yin DD, Cook JR. Cholesterol reduction yields clinical benefits: meta-analysis including recent trials. Clin Ther 2007;29(5):778-94.
9. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366(9493):1267-78.
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360(9326):7-22.
11. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350(15): 1495-504.
12. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352(14):1425-35.
13. McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement-- recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol 2006;22(11):913-27.
14. Russell MW, Huse DM, Miller JD, Kraemer DF, Hartz SC. Cost-effectiveness of HMG-CoA reductase inhibition in Canada. Can J Clin Pharmacol 2001;8(1):9-16.
15. Pilote L, Ho V, Lavoie F, Coupal L, Zowall H, Grover SA. Cost-effectiveness of lipid-lowering treatment according to lipid level. Can J Cardiol 2005;21(8):681-7.
16. Grover SA, Coupal L, Paquet S, Zowall H. Costeffectiveness of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors in the secondary prevention of cardiovascular disease: forecasting the incremental benefits of preventing coronary and cerebrovascular events. Arch Intern Med 1999;159(6):593-600.
17. Riviere M, Wang S, Leclerc C, Fitzsimon C, Tretiak R. Cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease in Canada. CMAJ 1997;156(7):991-7.
18. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term followup of the West of Scotland Coronary Prevention Study. N Engl J Med 2007; 357(15):1477-86.
19. Pedersen TR, Wilhelmsen L, Faergeman O, Strandberg TE, Thorgeirsson G, Troedsson L, et al. Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering. Am J Cardiol 2000;86(3):257-62.
20. Statistics Canada. Mortality, summary list of causes; Table 2: deaths by selected grouped causes, age group at time of death and sex, Canada. 2003. http://www.statcan.ca/english/freepub/84F0209 XIE/2003000/tablesectionlist.htm. (Accessed 5 Jul 2006).
21. Lampe FC, Whincup PH, Wannamethee SG, Shaper AG, Walker M, Ebrahim S. The natural history of prevalent ischaemic heart disease in middle-aged men. Eur Heart J 2000;21(13):1052-62.
22. Johansen H, Nair C, Mao L, Wolfson M. Revascularization and heart attack outcomes. Health Rep 2002;13(2):35-46.
23. Holroyd-Leduc JM, Kapral MK, Austin PC, Tu JV. Sex differences and similarities in the management and outcome of stroke patients. Stroke 2000;31(8):1833-7.
24. Jong P, Vowinckel E, Liu PP, Gong Y, Tu JV. Prognosis and determinants of survival in patients newly hospitalized for heart failure: a population-based study. Arch Intern Med 2002;162(15):1689-94.
25. Graham MM, Ghali WA, Faris PD, Galbraith PD, Norris CM, Knudtson ML. Survival after coronary revascularization in the elderly. Circulation 2002;105(20):2378-84.
26. Cardiac Care Network of Ontario. Annual report 2006/7. 2007. http://www.ccn.on.ca/4_2.php (Accessed 2 Feb 2009).
27. Gwinnutt CL, Columb M, Harris R. Outcome after cardiac arrest in adults in UK hospitals: effect of the 1997 guidelines. Resuscitation 2000;47(2):125-35.
28. Dennis MS, Burn JP, Sandercock PA, Bamford JM, Wade DT, Warlow CP. Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. Stroke 1993;24(6):796-800.
29. Mosterd A, Cost B, Hoes AW, et al. The prognosis of heart failure in the general population: The Rotterdam Study. Eur Heart J 2001;22(15):1318-27.
30. Ontario Ministry of Health and Long-Term Care. Ontario Case Costing Initiative. 2007. http://www.occp.com/. (Accessed 29 Jan 2009).
31. Ontario Ministry of Health and Long-Term Care. Ontario Drug Benefit Formulary/Comparative Drug Index. 2007. http://www.health.gov.on.ca/english/providers/p rogram/drugs/odbf_eformulary.html. (Accessed 29 Jan 2009).
32. Sullivan PW, Lawrence WF, Ghushchyan V. A national catalog of preference-based scores for chronic conditions in the United States. Med Care 2005;43(7):736-49.
33. Canadian Agency for Drugs and Technologies in Health. Guidelines for the economic evaluation of health technologies: Canada. 2006. http://www.cadth.ca.
34. Taylor DC, Pandya A, Thompson D, et al. Costeffectiveness of intensive atorvastatin therapy in secondary cardiovascular prevention in the United Kingdom, Spain, and Germany, based on the Treating to New Targets study. Eur J Health Econ 2008.
35. Mark DB, Knight JD, Cowper PA, DavidsonRay L, Anstrom KJ. Long-term economic outcomes associated with intensive versus moderate lipid-lowering therapy in coronary artery disease: results from the Treating to New Targets (TNT) Trial. Am Heart J 2008;156(4):698-705.
36. Bourgault C, Davignon J, Fodor G, et al. Statin therapy in Canadian patients with hypercholesterolemia: the Canadian Lipid Study -- Observational (CALIPSO). Can J Cardiol 2005;21(13):1187-93.
37. Perreault S, Blais L, Dragomir A, et al. Persistence and determinants of statin therapy among middle-aged patients free of cardiovascular disease. Eur J Clin Pharmacol 2005;61(9):667-74.
38. Lachaine J, Rinfret S, Merikle EP, Tarride JE. Persistence and adherence to cholesterol lowering agents: evidence from Regie de l'Assurance Maladie du Quebec data. Am Heart J 2006;152(1):164-9.
39. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidencebased pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007;297(2):177-86.
40. Wei L, MacDonald TM, Watson AD, Murphy MJ. Effectiveness of two statin prescribing strategies with respect to adherence and cardiovascular outcomes: observational study. Pharmacoepidemiol Drug Saf 2007;16(4):385- 92.
41. Thiebaud P, Patel BV, Nichol MB, Berenbeim DM. The effect of switching on compliance and persistence: the case of statin treatment. Am J Manag Care 2005;11 (11):670-4.
2. Heart and Stroke Foundation of Canada, Health Canada, Canadian Cardiovascular Society. Centre for Chronic Disease Prevention and Control HC, Canadian Cardiovascular Society, Heart and Stroke Foundation of Canada, editors. The Growing Burden of Heart Disease and Stroke in Canada 2003. 2003.
3. Manuel DG, Leung M, Nguyen K, Tanuseputro P, Johansen H. Burden of cardiovascular disease in Canada. Can J Cardiol 2003;19(9):997-1004.
4. Choi BK, Pak AW. A method for comparing and combining cost-of-illness studies: an example from cardiovascular disease. Chronic Dis Can 2002;23(2):47-57.
5. Health Canada. Economic burden of illness in Canada, 1998. 1998. http://www.phacaspc.gc.ca/publicat/ebic-femc98/index.html.
6. Alter DA, Stukel TA, Newman A. Proliferation of cardiac technology in Canada: a challenge to the sustainability of Medicare. Circulation 2006;113(3):380-7.
7. Genest J, Frohlich J, Fodor G, McPherson R. Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. CMAJ 2003;169(9):921-4.
8. Gould AL, Davies GM, Alemao E, Yin DD, Cook JR. Cholesterol reduction yields clinical benefits: meta-analysis including recent trials. Clin Ther 2007;29(5):778-94.
9. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366(9493):1267-78.
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360(9326):7-22.
11. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350(15): 1495-504.
12. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352(14):1425-35.
13. McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement-- recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol 2006;22(11):913-27.
14. Russell MW, Huse DM, Miller JD, Kraemer DF, Hartz SC. Cost-effectiveness of HMG-CoA reductase inhibition in Canada. Can J Clin Pharmacol 2001;8(1):9-16.
15. Pilote L, Ho V, Lavoie F, Coupal L, Zowall H, Grover SA. Cost-effectiveness of lipid-lowering treatment according to lipid level. Can J Cardiol 2005;21(8):681-7.
16. Grover SA, Coupal L, Paquet S, Zowall H. Costeffectiveness of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors in the secondary prevention of cardiovascular disease: forecasting the incremental benefits of preventing coronary and cerebrovascular events. Arch Intern Med 1999;159(6):593-600.
17. Riviere M, Wang S, Leclerc C, Fitzsimon C, Tretiak R. Cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease in Canada. CMAJ 1997;156(7):991-7.
18. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term followup of the West of Scotland Coronary Prevention Study. N Engl J Med 2007; 357(15):1477-86.
19. Pedersen TR, Wilhelmsen L, Faergeman O, Strandberg TE, Thorgeirsson G, Troedsson L, et al. Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering. Am J Cardiol 2000;86(3):257-62.
20. Statistics Canada. Mortality, summary list of causes; Table 2: deaths by selected grouped causes, age group at time of death and sex, Canada. 2003. http://www.statcan.ca/english/freepub/84F0209 XIE/2003000/tablesectionlist.htm. (Accessed 5 Jul 2006).
21. Lampe FC, Whincup PH, Wannamethee SG, Shaper AG, Walker M, Ebrahim S. The natural history of prevalent ischaemic heart disease in middle-aged men. Eur Heart J 2000;21(13):1052-62.
22. Johansen H, Nair C, Mao L, Wolfson M. Revascularization and heart attack outcomes. Health Rep 2002;13(2):35-46.
23. Holroyd-Leduc JM, Kapral MK, Austin PC, Tu JV. Sex differences and similarities in the management and outcome of stroke patients. Stroke 2000;31(8):1833-7.
24. Jong P, Vowinckel E, Liu PP, Gong Y, Tu JV. Prognosis and determinants of survival in patients newly hospitalized for heart failure: a population-based study. Arch Intern Med 2002;162(15):1689-94.
25. Graham MM, Ghali WA, Faris PD, Galbraith PD, Norris CM, Knudtson ML. Survival after coronary revascularization in the elderly. Circulation 2002;105(20):2378-84.
26. Cardiac Care Network of Ontario. Annual report 2006/7. 2007. http://www.ccn.on.ca/4_2.php (Accessed 2 Feb 2009).
27. Gwinnutt CL, Columb M, Harris R. Outcome after cardiac arrest in adults in UK hospitals: effect of the 1997 guidelines. Resuscitation 2000;47(2):125-35.
28. Dennis MS, Burn JP, Sandercock PA, Bamford JM, Wade DT, Warlow CP. Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. Stroke 1993;24(6):796-800.
29. Mosterd A, Cost B, Hoes AW, et al. The prognosis of heart failure in the general population: The Rotterdam Study. Eur Heart J 2001;22(15):1318-27.
30. Ontario Ministry of Health and Long-Term Care. Ontario Case Costing Initiative. 2007. http://www.occp.com/. (Accessed 29 Jan 2009).
31. Ontario Ministry of Health and Long-Term Care. Ontario Drug Benefit Formulary/Comparative Drug Index. 2007. http://www.health.gov.on.ca/english/providers/p rogram/drugs/odbf_eformulary.html. (Accessed 29 Jan 2009).
32. Sullivan PW, Lawrence WF, Ghushchyan V. A national catalog of preference-based scores for chronic conditions in the United States. Med Care 2005;43(7):736-49.
33. Canadian Agency for Drugs and Technologies in Health. Guidelines for the economic evaluation of health technologies: Canada. 2006. http://www.cadth.ca.
34. Taylor DC, Pandya A, Thompson D, et al. Costeffectiveness of intensive atorvastatin therapy in secondary cardiovascular prevention in the United Kingdom, Spain, and Germany, based on the Treating to New Targets study. Eur J Health Econ 2008.
35. Mark DB, Knight JD, Cowper PA, DavidsonRay L, Anstrom KJ. Long-term economic outcomes associated with intensive versus moderate lipid-lowering therapy in coronary artery disease: results from the Treating to New Targets (TNT) Trial. Am Heart J 2008;156(4):698-705.
36. Bourgault C, Davignon J, Fodor G, et al. Statin therapy in Canadian patients with hypercholesterolemia: the Canadian Lipid Study -- Observational (CALIPSO). Can J Cardiol 2005;21(13):1187-93.
37. Perreault S, Blais L, Dragomir A, et al. Persistence and determinants of statin therapy among middle-aged patients free of cardiovascular disease. Eur J Clin Pharmacol 2005;61(9):667-74.
38. Lachaine J, Rinfret S, Merikle EP, Tarride JE. Persistence and adherence to cholesterol lowering agents: evidence from Regie de l'Assurance Maladie du Quebec data. Am Heart J 2006;152(1):164-9.
39. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidencebased pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007;297(2):177-86.
40. Wei L, MacDonald TM, Watson AD, Murphy MJ. Effectiveness of two statin prescribing strategies with respect to adherence and cardiovascular outcomes: observational study. Pharmacoepidemiol Drug Saf 2007;16(4):385- 92.
41. Thiebaud P, Patel BV, Nichol MB, Berenbeim DM. The effect of switching on compliance and persistence: the case of statin treatment. Am J Manag Care 2005;11 (11):670-4.