Perspectives on low-density lipoprotein cholesterol goal achievement

ABSTRACT

Background: Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease (CHD). European and US guidelines now recommend lower LDL-C levels, particularly in high-risk patients. Although LDL-C treatment goals to reduce the risk of CHD are clear, many patients do not reach their LDL-C goals.

Objectives: Examine consensus guideline targets for LDL-C lowering in patients at high or very high cardiovascular risk; examine cholesterol goal achievement in clinical practice; evaluate the effectiveness of ezetimibe/statin and other adjunctive lipid-lowering treatments in achieving LDL-C goals; and consider ongoing controversies and the randomized controlled trials that may help to resolve or better illuminate them.

Methods: An English-language PubMed search was conducted to identify prospective randomized controlled trials, open-label studies, and retrospective and observational studies from 2001 (same year that the executive summary of the National Cholesterol Education Program's Adult Treatment Panel III was published) to present for an analysis of the effects of adjunctive therapies on LDL-C lowering and goal attainment in patients at elevated cardiovascular risk.

Results: Elevated LDL-C is the primary target of lipid-lowering therapy; aggressive lowering is of great benefit to those at high risk. Statins are recommended first-line lipid-lowering agents, with a long, well-regarded history of efficacy and safety. Not all patients, however, can achieve recommended LDL-C goals simply using starting doses of statins. For such patients, more intensive therapy utilizing high-dose statins or combination therapy, including statins combined with other lipid-lowering agents, such as ezetimibe, bile acid resins (BARs), or niacin, is warranted. Potential limitations of the present review include possible publication bias and the focus on pharmacotherapy rather than lifestyle modification and the important objective of multiple risk-factor modification to reduce absolute global cardiovascular risk.

Conclusions: With a well-established link between elevated LDL-C and cardiovascular risk, aggressive LDL-C lowering becomes particularly important. Patients needing intensive LDL-C lowering to achieve goals will often require adjunctive treatments, including ezetimibe, BARs, or niacin along with statins. Given both their high mg: mg potency in lowering LDL-C and favorable tolerability and patient acceptance/adherence profile, ezetimibe/statin combination regimens arguably provide the greatest likelihood for patients to reach new, lower LDL-C targets; however, efficacy and safety data of any adjunctive treatment, along with drug costs and patient adherence to treatment (partly related to complexity of the regimen) all need to be considered when determining the optimal regimen to achieve LDL-C goals in individual patients according to their baseline absolute cardiovascular risk, LDL-C level, and consensus LDL-C targets.

Key words: :

• Bile acid resins (sequestrants)
• Cholesterol
• Colesevelam
• Coronary heart disease
• Ezetimibe
• Low-density lipoprotein cholesterol
• Niacin
• Nicotinic acid
• Statins

Acknowledgments

Declaration of interest: This review was supported by Merck/Schering-Plough, North Wales, PA, USA. The sponsor had a role in reviewing and commenting on the manuscript; however, the author was responsible for final content. Assistance in manuscript preparation was provided by Stephen W. Gutkin, Rete Biomedical Communications Corp., Wyckoff, NJ, USA, and Wendy Horn, PhD, Insight Communications Group, Westfield, NJ, USA, with support from Merck. A. L. C. received an honorarium from Merck to prepare this review. He also discloses that he has received support from Merck, Schering- Plough, AstraZeneca and Pfizer as a speaker or a member of Advisory Boards. S. W. G. discloses that he has served as a paid consultant to or received grant support from Bristol-Myers Squibb, Novartis, Reliant, Schering-Plough and the study sponsor and/or its affiliates.