Supplements and Featured Publications, Cost-Effectiveness and Outcome Optimization Strategies in the Treatment of Residual Cardiovascular R, Volume 15, Issue 3

The introduction of statins has changed the landscape of pharmaceutical interventions for the treatment of cardiovascular disease (CVD), primarily through their recognized efficacy in reducing low-density lipoprotein (LDL) cholesterol levels. Major statin trials such as the Scandinavian Simvastatin Survival Study (4S) have demonstrated that lowering LDL cholesterol significantly reduces cardiovascular risk.1 Statins are generally well-tolerated and are the primary recommended lipid-modifying intervention in patients with coronary heart disease (CHD).2 Although statins provide significant benefits to various patient populations, CVD remains the leading cause of mortality worldwide and affects at least 70 million people in the United States.2 In 2008 the economic costs associated with CVD were estimated to be $448.5 billion.3

The articles in this supplement address 2 main issues surrounding the treatment of dyslipidemia and CVD. The first article, "Beyond LDL Cholesterol: The Role of Elevated Triglycerides and Low HDL Cholesterol in Residual CVD Risk Remaining After Statin Therapy," discusses our current understanding of the role of various lipid fractions in CVD risk, national guidelines for lipid values, and appropriate treatments to target multiple lipid abnormalities. Clinical trial data demonstrate that residual CVD risk remains even for people in whom LDL cholesterol levels have been aggressively reduced and are at target values.4 Data consistently indicate that high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol levels are independent risk factors for CHD events and the combination of both dramatically increases the risk of CHD.5 The National Cholesterol Education Program Adult Treatment Panel II guidelines recognize HDL cholesterol as a significant, independent risk factor for CVD and state that elevated TGs are a marker for increased CVD risk.6 These lipid parameters are secondary targets of therapy after LDL cholesterol goals have been met,6 and a 2004 report from Grundy et al recommended the possibility of adding a fibrate or niacin to LDL-lowering statin therapy.7 In recent studies, niacin/statin combination therapy8 and fenofibric acid/statin combination therapy9 have been demonstrated to be safe and effective for the treatment of multiple lipid abnormalities. Much of the second article within this supplement, "The Impact of Residual CVD Risk in the Managed Care Setting," discusses the achievement of lipid goals, including the primary goal of LDL cholesterol lowering, as well as secondary goals for HDL cholesterol, TGs, and non-HDL cholesterol. Several modeling studies based on patient information from large managed care databases have shown both the potential therapeutic benefits of extended-release niacin/simvastatin combination therapy as well as the potential cost savings associated with this treatment.10

This supplement outlines the significant progress that has been made in the treatment of CVD and dyslipidemia. However, much can still be done to decrease the burden of CVD as manifested through morbidity and mortality, as well as the increasing healthcare costs associated with the disease. The goal of the information presented in the following articles is to promote understanding of lipid parameters beyond LDL cholesterol in residual CVD risk and appropriate treatments that can be used to target these parameters. By addressing multiple lipid values, including HDL cholesterol, non-HDL cholesterol, and TGs through combination therapies, patient outcomes can be improved and potentially significant cost savings achieved.

1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383-1389.

2. Davidson MH. Overview of prevention and treatment of atherosclerosis with lipid-altering therapy for pharmacy directors. Am J Manag Care. 2007;13(suppl 10):S260-S269.

3. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117(4):e25-e146.

4. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437-2445.

5. Assmann G, Schulte H, von Eckardstein A. Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am J Cardiol. 1996;77(14):1179-1184.

6. 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) final report. Circulation. 2002;106(25):3143-3421.

7. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227-239.

8. Ballantyne CM, Davidson MH, McKenney J, Keller LH, Bajorunas DR, Karas RH. Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study. J Clin Lipidol. 2008;2:79-90.

9. Jones PH, Buttler SM, Davidson MH, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: a phase 3 study. J Clin Lipidol. 2008;2(3):218-219.

10. Balu S, Simko RJ, Burge RT, Quimbo R, Cziraky MJ. Impact of adhering to lipid management national guideline recommendations on cardiovascular events and costs in a managed care population. Value Health. 2008;11(3):A4.