Practice guidelines on the prevention and management of high cholesterol in adults are now available in many countries. These guidelines are expected to have significant implications for both primary and secondary prevention of cardiovascular disease. Although HMG-CoA reductase inhibitors are frequently prescribed for patients with hypercholesterolemia, a sufficient reduction in LDL-cholesterol levels can not always be achieved by its currently recommended dosage in Japan. Therefore, we compared the efficacy and safety of two three-month treatments; i. e. doubling the dosage of the HMG-CoA reductase inhibitor, fluvastatin to 40mg/day, and combined therapy using the HMG-CoA reductase inhibitor, fluvastatin at 20mg/day and colestimide at 3g/day. A cross-over procedure of the two treatments was applied in 8 patients (men/women=2/6, mean age 71 years) with hypercholesterolemia whose total cholesterol levels were more than 220mg/dl or LDL-cholesterol levels were more than 140mg/dl, despite treatment with 20mg/day of fluvastatin.
Mean total cholesterol levels at enrollment were 246±14mg/dl (mean±SD). The combined therapy decreased them significantly to 217±27mg/dl, whereas doubling the dosage regimen did not (239±25mg/dl). The combined therapy also decreased the calculated LDL-cholesterol levels significantly from 154±14mg/dl to 118±18mg/dl. In contrast, doubling the dosage of fluvastatin did not have a significant effect (141±23mg/dl). The levels of HDL-cholesterol and triglyceride remained unchanged with both treatments. Throughout the whole study period, there were no adverse events including elevation of CK, fasting blood sugar, and liver enzymes. We conclude that a combined therapy using an HMG-CoA reductase inhibitor and colestimide is efficacious and safe to obtain a significant reduction in total and LDL-cholesterol levels in patients with hypercholesterolemia refractory to the conventional statin treatment.