Combination drug therapy for hyperlipidemia

Abstract

Low‐dose combination hypolipidemic therapy may be the best approach to achieve the stringent target low‐density lipoprotein cholesterol (LDL‐C) levels recommended by the latest National Cholesterol Education Program guidelines in patients with multiple risk factors or existing coronary heart disease. Three randomized, double‐blind clinical trials have investigated the efficacy and safety of low‐dose fluvastatin, a new, wholly synthetic 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitor, in combination with bile acid sequestrants, fibric acid derivatives, and niacin, respectively. Low‐dose fluvastatin coupled with low‐dose cholestyramine proved to be significantly more effective than higher doses of either agent alone in reducing LDL‐C levels in patients with hypercholesterolemia. The combination was well tolerated, with most adverse events attributable to the gastrointestinal effects of cholestyramine. In patients with heterozygous familial hypercholesterolemia and severely elevated LDL‐C and triglyceride (TG) levels, the combination of fluvastatin with bezafibrate was equivalent to fluvastatin plus cholestyramine in lowering LDL‐C levels but was superior in raising high‐density lipoprotein cholesterol (HDL‐C) levels and reducing TG levels. Bezafibrate was considerably better tolerated than cholestyramine. Neither regimen was associated with untoward elevations in hepatic transaminase or creatine phosphokinase levels. Combination therapy with fluvastatin and niacin reduced LDL‐C levels by more than 30% in 90% of hypercholesterolemic subjects studied and decreased these levels by more than 40% in 60% of these subjects. The combination also increased HDL‐C levels by 36.4%, decreased TG levels by 32%, and reduced lipoprotein (a) levels by 37%. These modifications were achieved without adverse hepatic or myopathic effects. In summary, low‐dose fluvastatin can be safely and effective combined with either bile acids, fibrates, or niacin to achie greater reductions in LDL‐C than standard monotherapy. Copyright © 1994 Wiley Periodicals, Inc.