Novel Strategies for Managing Dyslipidemia: Treatment beyond Statins

Abstract

Purpose: This article reviews the current status of lipid–lowering drugs and their impact on cardiovascular morbidity and mortality. Because there is compelling evidence to suggest that substantial residual risk persists despite the use of current lipid–lowering treatments, novel strategies for managing dyslipidemia are discussed. Summary: Statins remain the drugs of choice for the treatment of dyslipidemia in patients with coronary heart disease or substantial risk factors for coronary heart disease. The evidence supporting the use of non–statin monotherapy for reductions in cardiovascular morbidity and mortality is examined. Furthermore, the evidence supporting the use of combinations of lipid–lowering drugs, primarily a statin plus another agent, for reductions in cardiovascular morbidity and mortality is discussed. Available clinical data for novel dyslipidemia drugs that can potentially expand on the current known benefits of statin therapy are reviewed. The cholesteryl ester transfer protein inhibitors, which predominantly increase high–density lipoprotein cholesterol levels and can also substantially lower low–density lipoprotein cholesterol levels, have the most robust clinical trial data, including some phase 3 study results. The proprotein convertase subtilisin/kexin type 9 inhibitors, which predominantly impact low–density lipoprotein cholesterol, are also being tested in phase 3 studies, but their widespread application may be limited by their need to be administered by injection. Peroxisome proliferator–activated receptor (PPAR) agonists with dual agonism of PPAR–α and PPAR–γ to optimize glycemic and lipid profiles may benefit patients with both diabetes and cardiovascular disease. The other novel lipid–lowering drugs are in earlier–phase human testing. Conclusion: Novel agents have the potential to be valuable additions to current treatment of dyslipidemia to reduce cardiovascular morbidity and mortality. These new drugs will not only have to be able to demonstrate an improvement in patients' lipid profiles, but will also have to be able to demonstrate that they reduce cardiovascular morbidity and mortality, typically in combination with statin therapy.