Dyslipidemia: Management Using Optimal Lipid-lowering Therapy

Matthew K Ito PharmD FCCP CLS FNLA

Disclosures

The Annals of Pharmacotherapy. 2012;46(10):1368-1381. 

In This Article

Abstract and Introduction

Abstract

Objective: To evaluate current approaches and explore emerging research related to dyslipidemia management.
Data Sources: MEDLINE (2004-April 2012) was searched for randomized controlled trials using the terms dyslipidemia and lipid-lowering therapy or statin (>1000 hits). Separate searches (MEDLINE, Google) identified meta-analyses (2010–2011), disease prevalence statistics, and current consensus guidelines (2004-July 2011). Additional references were identified from the publications reviewed.
Study Selection and Data Extraction: English-language articles on large multicenter trials were evaluated.
Data Synthesis: National Cholesterol Education Program Adult Treatment Panel III guidelines for the reduction of cardiovascular risk recommend the attainment of specific low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non–HDL-C) target values, based on an individual's 10-year risk of coronary heart disease or global risk. For most patients unable to achieve recommended lipid level goals with therapeutic lifestyle changes, statins are the first option for treatment. Results of large, well-controlled clinical trials have demonstrated that statins are effective in primary and secondary prevention of cardiovascular disease in diverse populations, including patients with diabetes and the elderly, and that intensive statin therapy provides more effective lipid goal attainment and significantly greater risk reduction in patients with coronary artery disease. Statin therapy is generally well tolerated but may increase the risk of myopathy. Statin use has been associated with increases in hepatic transaminases and an increased risk of diabetes, although the absolute risk of diabetes is low compared with the risk reduction benefit. Combination therapy including a statin may be appropriate for certain populations, but the risk reduction benefits of combination therapy remain unclear. Ezetimibe is an important treatment option for patients with hypercholesterolemia who do not tolerate intensive statin therapy. Although fibrates or niacin improves overall lipid profiles in patients with hypertriglyceridemia or dyslipidemia who are receiving statin therapy, their efficacy in reducing cardiovascular risk remains questionable and their use raises safety and tolerability concerns.
Conclusions: Intensifying lifestyle changes and statin dose should be utilized first in patients not achieving their LDL-C and non–HDL-C goals.

Introduction

Elevated low-density lipoprotein cholesterol (LDL-C) and elevated non–high-density lipoprotein cholesterol (non–HDL-C = total cholesterol minus HDL-C) are recognized as major risk factors for cardiovascular disease (CVD).[1] Most cardiovascular risk reduction strategies for individuals with dyslipidemia focus on controlling LDL-C and non–HDL-C levels, with specific targets based on a person's global risk.[2,3] The role of atherogenic particles such as the apolipoprotein B (apoB)-containing lipoproteins (particularly LDL) in development and progression of atherosclerosis is well established.[3] In patients with elevated triglycerides (TG) (200–499 mg/dL), other apoB-containing particles, such as very-low-density lipoprotein (VLDL), become more abundant and may contribute to the atherosclerotic process.[3] Atherosclerosis typically begins in early adulthood and progresses over several decades before symptoms appear. The build-up of atherosclerotic lesions may eventually cause angina or precipitate life-threatening thrombotic events such as myocardial infarction (MI).[4] The relationships between dyslipidemia, atherosclerosis, and CVD risk have become an emerging area of research and were assessed in MESA (titles of clinical trials reported in Appendix I). This prospective evaluation identified dyslipidemia as a powerful CVD risk factor in otherwise healthy adults.[5] In addition, a recent study suggested that atherosclerosis may be assessed using carotid intimamedia thickness (CIMT) and elevated coronary artery calcium in patients with hypercholesterolemia.[6]

A 15-year study assessing coronary heart disease (CHD) incidence demonstrated that approximately 3% of subjects had an LDL-C–lowering variation in the gene for the proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9).[7] PCSK9 affects cholesterol concentrations by degrading LDL receptors, leading to increased circulating concentrations of LDL-C.[8,9] Loss-of-function mutations in the gene for PCSK9 diminish this activity, lowering LDL-C levels. Results provide compelling evidence for significant CVD risk reduction associated with lifelong low LDL-C concentrations.[7]

Given the asymptomatic nature of atherosclerosis progression and the seriousness of potential CVD events, the timely implementation of prevention strategies focused on effective control of LDL-C and non–HDL-C concentrations is now recognized as a critical public health goal. In fact, many individuals with dyslipidemia do not achieve recommended lipid goals, suggesting a lost opportunity for decreasing cardiovascular risk. Cholesterol management is one of the top priorities promoted by Million Hearts, a national initiative to prevent 1 million MIs and strokes over the next 5 years.[10] Notably, when the much-anticipated Adult Treatment Panel (ATP) IV guidelines are released in the near future, current recommendations may need to be reconsidered.[11] This review discusses recommended CVD risk reduction pharmacotherapies for various patient populations with dyslipidemia in light of recently published clinical data and explores emerging areas of research.

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