The effects of therapy with 1 g of probucol and 20 g of colestipol were compared with those of the drugs used singly on 47 patients with hypercholesterolemia in a double-blind, double-placebo, diet-controlled, crossover trial that lasted 18 months. The probucol and colestipol combination, but neither drug alone, reduced mean serum low-density-lipoprotein (LDL)-cholesterol levels from 242 +/- 51 (SE) mg/dL during the diet and placebo phase to 171 +/- 41 mg/dL. Probucol significantly lowered high-density-lipoprotein (HDL)-cholesterol levels and increased LDL:HDL-cholesterol ratios. Combination therapy did not change LDL:HDL cholesterol ratios. Probucol alone or in combination reduced very-low-density-lipoprotein cholesterol levels, despite concomitant elevations of serum triglyceride levels caused by colestipol in the combination protocol. Gastrointestinal side effects of single drugs were abolished when drugs were used in combination. Compared with the values in the diet-placebo phase, LDL-cholesterol levels were reduced by more than 20% in 81% of patients, by more than 30% in 49%, and by more than 40% in 17%. This drug combination proved to be safer and have greater hypocholesterolemic effects in more patients than other marketed drug treatments.

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