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Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease

Robert S Rosenson, MD
Section Editor
Mason W Freeman, MD
Deputy Editor
Gordon M Saperia, MD, FACC


Lipid lowering with statins in patients with hypercholesterolemia has a proven survival benefit for both primary prevention (ie, in patients without clinical evidence of coronary disease) and secondary prevention (ie, in patients with established coronary disease), even when serum cholesterol concentrations are "normal" for the population or borderline high. Statins may also be beneficial in patients with heart failure. (See "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of cardiovascular disease" and "Statin therapy in patients with heart failure", section on 'Potential benefits and harms of statin therapy in HF'.)


The mechanisms by which lipid-lowering therapy (particularly with statins) is beneficial are incompletely explained by the serum low density lipoprotein (LDL) concentration at baseline or after treatment [1-6]. Although statins probably cause regression of atherosclerosis, an improvement in outcome can be demonstrated as early as six months (figure 1) [7,8], a time considered too early for significant regression. In addition, the amount of lesion regression is small compared with the magnitude of the observed clinical benefit.

A case-control study of adults with a first clinical presentation of coronary heart disease found that use of statins was associated with a decreased likelihood of that presentation being an acute myocardial infarction (odds ratio 0.45) and thus an increased likelihood of presenting with stable angina [9]. These observations suggest a mechanism of benefit with statins that might involve unstable coronary lesions.

Among the nonlipid mechanisms that may be involved are plaque stabilization, reduced inflammation, reversal of endothelial dysfunction, and decreased thrombogenicity [10,11].

Regression of atherosclerosis — Regression of the atherosclerotic lesions can occur after lipid lowering, without change in vessel wall thickness or vessel wall area, and may be clinically important [12]. One limitation to arteriographic studies is the relative lack of sensitivity to morphologic changes in atheroma, which can be better characterized by intracoronary ultrasonography (ICUS) [13], or to small changes, which might be detectable by other techniques such as B-mode ultrasonography for measurement of carotid intima thickness [14], electron beam or multidetector row computed tomography to detect coronary artery calcification [15], or high-resolution magnetic resonance imaging (MRI) [12]. (See "Diagnostic and prognostic implications of coronary artery calcification" and "Clinical utility of cardiovascular magnetic resonance imaging".)

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Literature review current through: Sep 2017. | This topic last updated: Dec 16, 2015.
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