There are numerous studies examining the pharmacoeconomic impact of HMG-CoA reductase inhibitor (statin) therapy on healthcare costs and outcomes. A recently published review demonstrated that the cost-benefit of these agents depends primarily on the risk of developing a coronary event. That is, as the risk of a coronary event increases, the cost-effectiveness ratio decreases. The typical cost per life-year saved (LYS) ranged from $US1800 to $US40 000 in patients with pre-existing coronary artery disease (CAD) and from $US15 000 to >$US1 million per LYS in patients without pre-existing CAD.
The literature is sparse on the pharmacoeconomics of medication non-compliance in patients taking statin medications. Data from two studies suggest that >75% compliance results in decreased coronary events such as myocardial infarction. However, retrospective database analyses indicate that the average compliance rate hovers around the 65% mark. Many of the studies discuss medication non-compliance as a factor, but do not independently analyse compliance pharmacoeconomically.
We examined the pharmacoeconomic impact of non-compliance using published studies that contained pharmacoeconomic data and/or compliance data. In general, we used the placebo arm of these published studies as the surrogate marker for complete non-compliance. The results suggest that for almost 100% compliance versus initial non-compliance, the cost effectiveness of statin medications ranges from $US4500 to over $US250 000 per LYS depending on patient age, presence or absence of risk factors and whether the statin is being used for primary or secondary prevention.
Alternate-day or weekly dosing studies were also used to examine the impact of compliance on cost and health outcomes. Alternate-day dosing represented 50% compliance and weekly dosing 29% compliance. Less than full compliance had the expected effect of worse health outcomes and lower drug costs. However, the studies were small and not designed as true pharmacoeconomic studies looking at the relationship between medication compliance and cost.
The results of this review suggest that there needs to be further examination of the relationship between compliance with statins and cost effectiveness, and studies need to include compliance in their data collection and analysis.
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The authors have no conflicts of interest directly relevant to the content of this review. Each author has contributed equally to the development and writing of this review. No sources of funding were used in the preparation of this manuscript; however, Dr Petersen did receive a grant from Merck US Human Health to conduct pharmacoeconomic research in medication compliance, with a component of that research on statins.
Task Force for Compliance. Noncompliance with medication regimens: an economic tragedy: emerging issues in pharmaceutical cost containing. Washington, DC: National Pharmaceutical Council, 1994: 1–32Google Scholar
McGhan WF, Peterson AM. Pharmacoeconomic impact of noncompliance. US Pharmacist Impact 2001, 3–13Google Scholar
Stamler J, Wentworth D, Neaton JD. Prevalence and prognostic significance of hypercholesterolemia in men with hypertension: prospective data on the primary screenees of the Multiple Risk Factor Intervention Trial. Am J Med 1986; 80 (2A): 33–9PubMedCrossRefGoogle Scholar
Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279 (20): 1615–22Google Scholar
Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia: West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333 (20): 1301–7PubMedCrossRefGoogle Scholar
Scandinavia Simvastatin Survival Study group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344 (8934): 1383–9Google Scholar
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339 (19): 1349–57CrossRefGoogle Scholar
Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335 (14): 1001–9PubMedCrossRefGoogle Scholar
Heart Protection Study Collaborative Group. MRCBHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360 (9326): 7–22CrossRefGoogle Scholar
Top 200 brand-name drugs by units in 2002. Drug Topics 2003; 60–2Google Scholar
Meichenbaum D, Turk DC. Facilitating treatment adherence: a practitioner’s guidebook. New York: Plenum, 1987CrossRefGoogle Scholar
Flanagan A, Gartenmann T, Lovich D, et al. The hidden epidemic: finding a cure for unfilled prescriptions and missed doses [online]. Available from URL: http://www.beg.com/publications/files/TheHiddenEpidemic_Rpt HCDec03.pdf [Accessed 2003 Dee 18]Google Scholar
Iskedjian M, Einarson TR, MacKeigan LD, et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin Ther 2002; 24 (2): 302–16PubMedCrossRefGoogle Scholar
Beardon PHG, McGilchrist MM, McKendrick AD, et al. Primary non-compliance with prescribed medication in primary care. BMJ 1993; 307: 846–8PubMedCrossRefGoogle Scholar
Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc (Wash) 2001; 41: 192–9Google Scholar
Secnik K, Pathak DS, Cohen JM. Postcard and telephone reminders for unclaimed prescriptions: a comparative evaluation using survival analysis. J Am Pharm Assoc (Wash) 2000; 40: 243–51Google Scholar
McCaffrey DJ, Smith MC, Banahan BF, et al. The financial implications of initial noncompliance: an investigation of unclaimed prescriptions in community pharmacies. J Res Pharmaceut Econ 1995; 6: 39–64CrossRefGoogle Scholar
Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30PubMedGoogle Scholar
Yusuf S, Wittes J, Probstfield J, et al. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA 1991; 266: 93–8PubMedCrossRefGoogle Scholar
Wei L, Wang J, Thompson P, et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart 2002; 88: 229–33PubMedCrossRefGoogle Scholar
Hughes DA, Bagust A, Haycox A, et al. Accounting for noncompliance in pharmacoeconomic evaluations. Pharmacoeconomics 2001; 19: 1185–97PubMedCrossRefGoogle Scholar
Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs: do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995; 332: 1125–31PubMedCrossRefGoogle Scholar
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285 (19): 2486–97Google Scholar
Mansur AP, Mattar APL, Tsubo CE, et al. Prescription and adherence to statins of patients with coronary artery disease and hypercholesterolemia. Arq Bras Cardiol 2001; 76: 115–8Google Scholar
Avorn J, Monette J, Lacour A, et al. Persistence of use of lipidlowering medications: a cross-national study. JAMA 1998; 279: 1458–62PubMedCrossRefGoogle Scholar
Morrison A, Glassberg H. Determinants of the cost-effectiveness of statins. J Manag Care Pharm 2003; 9: 544–51PubMedGoogle Scholar
Urquhart J. Pharmacoeconomic consequences of variable patient compliance with prescribed drug regimens. Pharmacoeconomics 1999 Mar; 15 (3): 217–28PubMedCrossRefGoogle Scholar
Peterson AM, Sanoski C, McGhan WF. Total direct medical and drug costs of non-adherence to statin therapy within the first year of treatment: International Society for Pharmacoeco nomics and Outcomes Research [abstract]. Value Health 2002; 3: 167CrossRefGoogle Scholar
Peterson AM, McGhan WF. A decision analysis model for enhancing medication adherence in patients taking statins. Value Health 2001; 4: 500CrossRefGoogle Scholar
Hamilton VH, Racicot FE, Zowall H, et al. The cost effectiveness of HMG-CoA reductase inhibitors to prevent coronary heart disease: estimating the benefits of increasing HDL-C. JAMA 1995; 273: 1032–8PubMedCrossRefGoogle Scholar
Martens LL, Guibert. Cost-effectiveness analysis of lipid-modifying therapy in Canada: comparison of HMG-CoA reductase inhibitors in the primary prevention of coronary heart disease. Clin Ther 1994; 16: 1052–62PubMedGoogle Scholar
Berio P, Mubro V, Gaddi A, et al. Cost-effectiveness analysis for statin therapies in the primary prevention of coronary heart disease in Italy. Clin Drug Invest 2000; 20: 109–21CrossRefGoogle Scholar
Ashraf T, Hay JW, Pitt B, et al. Cost effectiveness of pravastatin in secondary prevention of coronary artery disease. Am J Cardiol 1996; 78: 409–14PubMedCrossRefGoogle Scholar
Ganz DA, Kuntz KM, Jacobson GA, et al. Cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy in older patients with myocardial infarction. Ann Intern Med 2000; 132: 780–7PubMedGoogle Scholar
Johannsenn M, Jonsson B, Kjekshus J, et al. Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary health disease: Scandinavian Simvastatin Survival Study Group (4S). N Engl J Med 1997; 336: 332–6CrossRefGoogle Scholar
Prosser LA, Stinnett AA, Goldman PA, et al. Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Intern Med 2000; 132: 769–79PubMedGoogle Scholar
Riviere M, Wang S, Lecrlerc, et al. Cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease in Canada. CMAJ 1997; 156: 991–7PubMedGoogle Scholar
Metz CA, Lucas KH. Alternate-day dosing of HMG-CoA reductase inhibitors for cholesterol reduction. Ann Pharmacother 2001; 35 (4): 496–500PubMedCrossRefGoogle Scholar
Iliff D. Weekly versus daily dosing of atorvastatin. J Fam Pract 2002; 51: 365–6PubMedGoogle Scholar
Matalka MS, Ravnan MC, Deedwania PC. Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Am Heart 2002; 144: 674–7Google Scholar