New horizons in combination drug therapy for hypercholesterolemia

A modest number of hypolipidemic drugs are currently available, and their use as single agents frequently fails to adequately control patients with severe hypercholesterolemia. Combined-drug regimens afford the opportunity to maximize the cholesterol-lowering effects of drugs that have different mechanisms of action and, at the same time, minimize potential side effects. The bile acid sequestrants (cholestyramine and colestipol) enhance fecal sterol excretion and are nonsystemically acting; they have provided the cornerstone for the majority of the established combined-drug regimens. The most effective regimens have used bile acid sequestrants in combination with nicotinic acid, or more recently, lovastatin or simvastatin. Combinations in which fenofibrate, bezafibrate, or probucol have been used with cholestyramine or colestipol have also been shown to be useful although the low-density-lipoprotein-lowering effect of probucol appears quite variable. The use of low doses of bile acid sequestrants (4-8 g/day of cholestyramine or 5-10 g/day of colestipol) in combination with lovastatin, simvastatin, or probucol provides a therapeutic regimen that is usually well tolerated, shows additive lipid lowering, and is cost effective.