Lipid-Lowering Targets: Is LDL-C the Best We Got?

Merle Myerson, MD, EdD


July 08, 2015

In This Article

Introduction and Background

With the introduction of the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults[1] came a radical departure from existing guidelines. Targets for low-density lipoprotein cholesterol (LDL-C), or indeed any lipid measure, were eliminated. This brought about wide debate[2,3]—played out not only in the medical community but on the front pages of newspapers and in the TV news.

Many experts believe that targets are important and valuable—for both the provider and the patient. Existing guidelines in Europe[4], Canada,[5] and by the International Atherosclerosis Society[6] and recommendations by the National Lipid Association (NLA)[7] include LDL-C targets based on risk scores, as did the previous National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III).[8]

The recent IMPROVE-IT trial[9] provided evidence that "lower is better" for LDL-C, supporting continued utility of lipid targets in high-risk patients. This study of more than 18,000 post-acute coronary syndrome patients on simvastatin therapy randomly assigned to have ezetimibe or placebo added showed an additional 12.8 mg/dL reduction in LDL-C at 1 year with ezetimibe. Baseline LDL-C was 95 mg/dL in both groups and was reduced to 69.9 mg/dL at 1 year in the statin-only group vs 53.2 mg/dL with ezetimibe. There was a significant reduction in cardiovascular (CV) events, including a 10% reduction in CV death, myocardial infarction, and stroke in the group that received ezetimibe. Although this study was for secondary prevention, many feel that benefits would extend to those who do not have manifest disease.

If lipid targets are back in play, can we do better than LDL-C? This review is intended to provide a brief background on the benefits and limitations of LDL-C as a target for therapy. In addition, a discussion of other lipid parameters that reflect atherosclerotic particle burden will be provided, as will suggestions on steps clinicians can follow in managing dyslipidemia.


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