Combination drug therapy in the treatment of severe hyperlipidaemia

Abstract Each of the four classes of hypolipidaemic drugs have different mechanisms of action: β-hydroxy-/gb-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (vastatins) reduce cholesterol synthesis in the liver and mainly reduce low density lipoprotein (LDL), also decreasing very low density lipoprotein (VLDL) and increasing high density lipoprotein (HDL). Fibrates reduce VLDL and, to a lesser extent, LDL and increase HDL. Bile acid sequestrants increase cholesterol flux to bile salt synthesis. They reduce LDL and can lead to a paradoxical increase in VLDL levels. Nicotinic acid reduces fatty acid flux to the liver; it mainly reduces VLDL, and consequently LDL is decreased and HDL increased. Vastatins and resins are, therefore, the drugs of first choice in the treatment of hypercholesterolaemia, while nicotinic acids and fibrates are the drugs of first choice for combined hyperlipidaemia. When monotherapy with vastatins in hypercholesterolaemia fails to reduce LDL to target levels, the most logical and potent combination therapy is with resins. As these two classes of drugs enhance each other's effects, a relatively low dose of resin can be used, thus reducing the level of side-effects and increasing drug compliance. Combination therapy with vastatins and nicotinic acid may be tried in cases where both VLDL and LDL are elevated, if monotherapy with either class of drug proves inadequate. Triple therapy with vastatins, resins and nicotinic acid is the most potent combination available today.