The Long-term Effects of Colestipol Hydrochloride on Serum and Lipoprotein Lipids in Patients with Heterozygous Familial Hypercholesterlomia

Abstract

Effects of long-term (48 weeks) treatment with colestipol hydrochloride, a bile acid sequestrant, in 33 subjects with heterozygous familial hypercholesterolemia are reported in this paper.
Treatment with 10 or 15 grams a day produced significant (p<0.001) reductions in the serum cholesterol levels (mean reduction of 20%) from 351±63mg/dl (mean±SD) to 272±54mg/dl after 4 weeks of treatment, and the mean cholesterol values were 268-283mg/dl (-17%- -22%) during the 4th week through the 48th week. Eleven subjects with pretreatment cholesterol levels over 400mg/dl showed a significantly higher reduction (27.2±12.3%) than the other patients (15.8±13.1%) after 48 weeks. There was no changes in serum triglyceride levels throughout the observation period. The phospholipid and β-lipoprotein levels fell significantly from 302±47mg/dl and 678±141mg/dl to 266±38mg/dl and 541±111mg/dl after 48 weeks, respectively. The high density lipoprotein-cholesterol (HDL-C) levels increased significantly from 36.2±9.4mg/dl to 43.0±8.7mg/dl after 48 weeks. The decrease of phospholipid and β-lipoprotein, and the increase of HDL-C were significant at each observation time.
Ultracentrifugal analysis of fifteen patients revealed a significant reduction of low density lipoprotein (LDL)-cholesterol from 274±68mg/dl to 183±50mg/dl (-31.5%). LDL-triglyceride and LDL-phospholipid also decreased significantly, from 52mg/dl to 41mg/dl and 155mg/dl to 115mg/dl, respectively. A slight and insignificant increase of very low density lipoprotein (VLDL)-triglyceride levels (from 51mg/dl to 66mg/dl) was observed, but indivisual changes were variable. In contrast to the increase of HDL-C measured by precipitation method, the cholesterol concentration in d>1.063g/ml fraction showed no significant changes.
Long-term treatment with colestipol showed no effects on Achilles tendon thickness, but a skin xanthoma disappeared in a patient. A patient with angina pectoris requiring medication reported subjective improvement.
No serious side effects were attributed to the drug treatment. Four patients claimed constipation. One patient complained of abdominal fullness after five days of therapy. The levels of GOT, GPT and alkaline phosphatase elevated in five patients, but returned to normal or slightly elevated levels in four of the five patients.
In conclusion, colestipol hydrochloride significantly reduced serum and LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia. The absence of severe side effects in long-term therapy indicates the efficacy of this resin in the treatment of this hereditary metabolic disease which represents an important risk factor in atherosclerosis.