高コレステロール血症におけるHMG-CoA還元酵素阻害剤プラバスタチン投与時のエスケープ現象とシンバスタチンの効果

Abstract

Although the hydroxymethylglutaryl coenzyme A reductase inhibitor is a powerful therapeutic agent in the treatment of hypercholesterolemia, an escape phenomenon has been reported. We sought to determine the effects of simvastatin in patients associated with the escape phenomenon following pravastatin therapy. Twenty-one patients with hypercholesterolemia (mean age:58;age range:25 to 75;seven men, 14 women) were studied. All patients had been given pravastatin (10mg/day) for at least 12 weeks. After the occurrence of the escape phenomenon, pravastatin was replaced by simvastatin (5mg/day). Serum lipids were measured periodically. Although total serum cholesterol levels showed significant decreases following pravastatin therapy (from 281±4mg/dl to 224±6mg/dl), such levels increased to 255±6mg/dl after 12 to 116 weeks. By replacing pravastatin with simvastatin, total serum cholesterol levels fell to 220±5mg/dl after 12 weeks and remained low (222±8mg/dl, n=13) even after 32 weeks. However, the total serum cholesterol levels tended to increase after 40 weeks. The serum LDL-cholesterol levels revealed changes that paralleled those of the total cholesterol levels, while serum HDL-cholesterol and the triglyceride levels did not reveal significant changes. These results suggest that simvastatin is a useful therapeutic alternative when the escape phenomenon occurs involving the use of pravastatin, although a similar phenomenon may occur even with simvastatin following long-term administration.