Pravastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia.

Pravastatin is an HMG-CoA reductase inhibitor which reduces plasma cholesterol levels by inhibiting de novo cholesterol synthesis and increasing the receptor-mediated catabolism of low density lipoprotein (LDL). Several large multicentre placebo-controlled trials have shown that pravastatin reduces total and LDL-cholesterol levels in a dose-proportional manner in patients with familial or nonfamilial hypercholesterolaemia. Reductions in LDL-cholesterol levels reported in the largest study were 18% (10 mg/day), 23% (20 mg/day) and 31% (40 mg/day) after 12 weeks. Once-daily administration appears to be as effective as two daily doses. Pravastatin consistently increases HDL-cholesterol levels and decreases levels of total triglycerides but these changes are not dose dependent. At the study dosages used, the antihypercholesterolaemic effects of pravastatin were superior to those of bezafibrate and clinofibrate, and were similar to those of simvastatin, lovastatin, gemfibrozil and cholestyramine although in some studies a trend towards a superior effect with pravastatin was seen. Pravastatin did not reduce HDL-cholesterol like probucol, or increase triglyceride levels like cholestyramine. Combined treatment with pravastatin and cholestyramine or colestipol enhances the cholesterol-lowering effects of either drug administered alone and offsets the increase in total triglyceride levels seen with cholestyramine or colestipol therapy. Pravastatin is well tolerated during treatment of up to 24 months but longer term tolerability has not yet been established. The effect of provastatin on cardiovascular events related to elevated plasma cholesterol levels is under investation in several large scale regression and primary and secondary prevention trials.(ABSTRACT TRUNCATED AT 250 WORDS)