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Combination therapy.

Abstract

Adult Treatment Panel III (ATP III) guidelines recommend specific treatment targets for low-density lipoprotein cholesterol (LDL-C) levels according to an individual.s short-term and long-term risk for coronary heart disease (CHD). Therapeutic lifestyle changes are recommended for all patients at any level of risk for CHD. Although most patients will achieve some LDL-C lowering with lifestyle modification, ATP III recognizes that a majority of patients with dyslipidemia will require drug therapy to reach their LDL goal. Surveys of physicians. practices suggest that only a small percentage of patients enrolled in an active treatment program actually achieve their LDL-C target. In addition, other surveys suggest that not all patients who are treatment candidates are receiving assessment. From a medication perspective, either up-titration of statin dose or the use of drug combinations should further enhance the likelihood of achieving target lipid levels. Combination therapies that target both the endogenous and exogenous pathways of cholesterol synthesis are particularly attractive. This paper reviews the pharmacotherapeutic effects of combination therapy, summarizes the strengths and weaknesses of current lipid-lowering drug combinations, and identifies the potential contribution of the novel cholesterol absorption inhibitor, ezetimibe, to the LDL-C treatment algorithm.

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BibTeXRIS

Margo A Denke. Combination therapy.. https://doi.org/10.18553/jmcp.2003.9.s1.17

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Proportion of oxidized LDL relative to plasma apolipoprotein B does not change during statin therapy in patients with heterozygous familial hypercholesterolemia.

OBJECTIVE: Circulating oxidized low-density lipoprotein (LDL) has been shown to be a useful marker for identifying patients with coronary heart disease (CHD) and persons at high cardiovascular risk. The effect of cholesterol-lowering therapy on plasma level of oxidized LDL is not clear. METHODS AND RESULTS: We investigated effects of cholesterol lowering by therapeutic intervention (2 years) with atorvastatin (80 mg daily) and simvastatin (40 mg daily) on circulating oxidized LDL (absolute level and in proportion to plasma apolipoprotein B) in relation to atherosclerosis progression (carotid intima-media thickness, carotid IMT) and to inflammation (high-sensitivity C-reactive protein, hsCRP) in 115 stable patients with heterozygous familial hypercholesterolemia (FH). Atorvastatin and simvastatin reduced plasma-oxidized LDL (-43 and -35%, respectively) in proportion to the decrease in plasma apolipoprotein B. Neither absolute nor relative level of oxidized LDL correlated with carotid IMT or hsCRP at baseline. Also changes in levels of circulating oxidized LDL were not related to changes in carotid IMT and hsCRP. CONCLUSIONS: In familial hypercholesterolemia-oxidized LDL carried in plasma is strongly associated with apolipoprotein B but not with inflammation nor with carotid IMT, and statin treatment does not reduce oxidized LDL relative to apolipoprotein B.

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