Comparative evaluation of fibric acid derivatives and HMG-CoA reductase inhibitors

• Published in: Atherosclerosis Vol. 97; pp. S11 - S19
• Main Author: Brewer, H.B.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.12.1992; Elsevier
• Subjects: Apolipoproteins; Biological and medical sciences; Fibrates; General and cellular metabolism. Vitamins; HMG-CoA reductase; HMG-CoA reductase inhibitors; Hypercholesterolaemia; Hypertriglyceridaemia; Lipoprotein lipase; Lipoprotein metabolism; Lipoprotein subfractions; Medical sciences; Pharmacology. Drug treatments; Hypertriglyceridaemia; HMG-CoA reductase; HMG-CoA reductase inhibitors; Lipoprotein subfractions; Lipoprotein lipase; Fibrates; Lipoprotein metabolism; Hypercholesterolaemia; Apolipoproteins
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(92)90159-E

Fibric acid derivatives (fibrates) and β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are hypolipidaemic agents with contrasting mechanisms of action. Fibrates have multiple effects on capillary and hepatic enzymes involved in fatty acid and triglyceride metabolism. The principal lipid-lowering effect of fibrates appears to be mediated through increased activity of lipoprotein lipase, but other hepatic enzymes are also affected by these drugs. By increasing the activity of lipoprotein lipase, fibrates have a pronounced triglyceride-lowering effect; the response of plasma cholesterol to fibrates, however, varies with the nature of the underlying lipid abnormality. Some elevation of low density lipoprotein (LDL) may occur in hypertriglyceridaemic patients, apparently as a result of reduced non-receptor-mediated clearance of LDL. In hypercholesterolaemic patients, fibrates reduce triglyceride and, to a lesser extent, plasma LDL levels; the reduction in LDL may be related to stimulation of receptor-mediated clearance. Reductase inhibitors are the most potent cholesterol-lowering drugs available and have a clearly defined mode of action. By inhibiting HMG-CoA reductase, the rate-limiting step in hepatic cholesterol synthesis, these agents induce a compensatory increase in the synthesis and expression of hepatic LDL receptors, resulting in reduction of plasma LDL levels. There is also evidence that reductase inhibitors inhibit the synthesis of LDL and apolipoprotein (apo) B, the principal surface protein in LDL. This inhibitory action may be especially beneficial in patients with combined hyperlipidaemia, in whom there is evidence of overproduction of LDL and apo B. Reductase inhibitors also reduce triglyceride levels, but to a lesser extent than LDL; their triglyceride-lowering efficacy is not as marked as that of fibrates. LDL is regarded as the principal atherogenic lipoprotein and preference may, therefore, be given to reductase inhibitors when contemplating lipid regulation for the prevention of CHD. Fibrates, however, offer advantages in the management of patients with predominant or exclusive hypertriglyceridaemia.