Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia.

Abstract

SUMMARY Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type 1I hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean ± SEM): C and LDL-C from 412.7 ± 24.4 and 331.1 ± 22.8 to 270 ± 11.0 and 188.1 ± 13.8, respectively (p < 0.001 in each instance) over 7-71/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances.COLESTIPOL, a tetraethylene-pentamine and epichlorhydrin copolymer, is a synthetic anionic bile acid-binding resin which sequestrates bile acids in the intestinal tract to reduce their reabsorption.1 2 This stimulates an increased rate of hepatic sterol synthesis. However, if increased hepatic cholesterol biosynthesis is insufficient to compensate for the exaggerated cholesterol degradation into bile acids, hepatic cholesterol pool may be reduced,3 and will result in lowering of plasma cholesterol concentration. Several colestipol studies of different durations in man have reported serum cholesterol reductions of 14-20% from the pretreatment or placebo treatment levels.2' [4][5][6][7][8] Since hypercholesterolemia in patients with familial type II hyperlipoproteinemia is caused at least partially by a decrease in cholesterol-rich low density

Extracranial carotid arterial disease in patients with familial hypercholesterolemia and coronary artery disease treated with colestipol and nicotinic acid.

“…10 " Serum lipid-lipoprotein analyses were performed 3 times at 2-week intervals while the patient was on the therapeutic diet to document limited hypocholesterolemic response to diet. After a 6-week dietary modification period, treatment of LDL cholesterol abnormality was augmented by combined administration of 10 g colestipol before each meal, and 2.0-2.5 g nicotinic acid 3 times a day after meals.…”

Mechanisms of Lipid-Lowering Agents

“…The loss of bile acids leads to a reduction of the body pools of cholester ol. This may bring about a regression of ten don xanthomas and possibly of atheroscle rotic lesions [5]. Another consequence is a compensatory increase in cell-surface lowdensity-lipoprotein (LDL) receptors in the liver, together with an increased activity of HMG-CoA reductase, the key enzyme in cholesterol biosynthesis.…”

Effect of concomitant colestipol hydrochloride administration on the bioavailability of diltiazem from immediate‐ and sustained‐release formulations

“…Colestipol hydrochloride (colestipol) is a hygroscopic, water insoluble, high molecular weight, basic anion-exchange resin which is orally effective in decreasing serum concentrations of total and LDL-cholesterol [1][2][3]. Colestipol lowers circulating cholesterol by binding bile acids in the intestine forming a complex that is excreted in the feces, and thus interrupts the enterohepatic recycling of bile acids.…”