COMPARATIVE EFFICACY AND SAFETY OF PRAVASTATIN AND CHOLESTYRAMINE ALONE AND COMBINED IN PATIENTS WITH HYPERCHOLESTEROLEMIA

Backgrounds: Treatment of severe hypercholesterolemia often requires h igh-dose therapy with a hydroxymethylglutaryl-coenzyme A reductase inh ibitor alone or in combination with bile acid-binding resin. We evalua ted the efficacy and safety, of pravastatin, a new hydroxymethylglutar yl-coenzyme A reductase inhibitor with hydrophilic selectivity, alone and in combination with cholestyramine. Methods: Pravastatin was studi ed at doses of 20 or 40 mg twice daily alone or 20 mg twice daily with cholestyramine, 12 g twice daily, vs placebo in a randomized, double- blind multicenter study of 311 patients for 8 weeks and in continued t herapy through 24 weeks. Results: After 8 weeks of therapy, pravastati n in a dosage of 20 mg twice daily reduced low-density lipoprotein cho lesterol levels by 31%, whereas a dosage of 40 mg twice daily reduced low-density lipoprotein cholesterol levels by 38%. Cholestyramine, 24 g daily alone, reduced low-density lipoprotein cholesterol levels by 3 2%. Cholestyramine combined with 40 mg of pravastatin reduced the leve l by 51%. Pravastatin, 40 or 80 mg daily, reduced the triglyceride lev el by 13% to 19%, resin alone increased the triglyceride level by 21%, and no change was seen with combined therapy. High-density lipoprotei n cholesterol levels increased by about 5% regardless of regimen. Simi lar effects were seen at 24 weeks. Symptoms reported were indistinguis hable among placebo and pravastatin users and were less than with chol estyramine alone or cholestyramine in combination with pravastatin. El evations of liver enzyme levels were small in all groups, indistinguis hable between resin and pravastatin, and were highest when the two dru gs were combined. Plasma creatine kinase levels did not increase in an y treatment group. Conclusions: Pravastatin treatment of hypercholeste rolemia is highly effective and well tolerated alone and in combinatio n with bile acid-binding resin and shows no tendency to increase muscl e enzyme levels.