An Evidence-Based Approach to the Use of Combination Drug Therapy for Mixed Dyslipidemia

Dyslipidemia is one of the major modifiable risk factors for coronary heart disease (CHD), the leading killer of men and women in the United States [1]. Most patients with CHD have multiple lipid abnormalities, and a management approach focusing exclusively on lowdensity lipoprotein cholesterol (LDL-C) reduction fails to address the added atherogenic potential that has been shown to exist when other CHD risk factors are present. The condition known as mixed dyslipidemia (ie, elevated LDL-C and triglyceride levels combined with decreased levels of high-density lipoprotein cholesterol [HDL-C]) is commonly seen in patients with type 2 diabetes and metabolic syndrome [2]. In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program (ATP III) established LDL-C and non-HDL-C treatment goals for patients with mixed dyslipidemia [3]. These recommendations were recently updated to reflect new data from 5 major clinical trials of relevance to cholesterol-lowering therapy, and the treatment goals for patients at highest risk were revised to be even more aggressive (Table 1) [1]. These more aggressive goals will increase the number of patients who will require therapy with 2 or 3 lipid-lowering drugs. Some clinicians have been reluctant to use combination therapy because of safety concerns, particularly in light of the withdrawal of cerivastatin from the market. This article reviews the available evidence to address the question of which drug or drug combination should be used in patients with multiple lipid abnormalities. Studies were identified by searching MEDLINE and EMBASE from 1966 to November 2005, as well as the Cochrane Library of references and clinical trials. All languages were included.