Simvastatin is the second in the class of compounds known as hydroxy-methylglutaryl-
coenzyme A reductase inhibitors to be extensively studied in humans. The
drug has now been given to over 1,800 patients with primary
hypercholesterolemia for periods of up to two years. In the range of dosage from 10 to 40 mg once daily,
therapy is associated with reductions of up to 30 percent in total
cholesterol and 40 percent in
low-density lipoprotein cholesterol levels, as well as with increases of approximately 10 percent in
high-density lipoprotein cholesterol levels. The most common clinical adverse experiences are mild gastrointestinal effects and
headache, which seldom require discontinuation of
therapy. Elevations of
creatine kinase (skeletal muscle
isoenzyme) levels to more than three times the upper limit of the normal range have been seen in about 3 percent of patients, but also have seldom required discontinuation of
therapy. Conversely, elevations of hepatic
transaminase levels to more than three times the upper limit of the laboratory normal range have been seen in about 1.5 percent of patients and have caused discontinuation of
therapy in 0.6 percent of patients treated.
Simvastatin appears to be an effective and well-tolerated agent for the treatment of primary
hypercholesterolemia and, as further study confirms long-term safety and efficacy, it should become a useful addition to the therapeutic armamentarium.