Central Nervous System Effects of HMG CoA Reductase Inhibitors: Lovastatin and Pravastatin on Sleep and Cognitive Performance in Patients with Hypercholesterolemia

Abstract

Sleep disturbances and decrements of daytime performance have been attributed to HMG‐CoA reductase inhibitors. As a rule, lipophilic compounds more readily cross the blood‐brain barrier and are more likely to affect central nervous system function. The authors compared the effects of lovastatin (40 mg), a lipophilic compound, to pravastatin (40 mg), a hydrophilic compound, in a 6‐week, double‐blind, randomized, placebo‐controlled, three‐way Latin square design, cross‐over study on 22 men with hypercholesterolemia. Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low‐fat (<30%), low‐cholesterol (<300 mg/day) diet. Compared with placebo, there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures: changes in total sleep time, time in each sleep stage, sleep efficiency, sleep latency, REM density, REM activity, and number of arousals. Similarly, there were no effects of the two drugs on measures of cognitive performance. A significant increase in the duration of nocturnal tumescence (NPT) was observed after 2 weeks of treatment with both study drugs. This effect was not significant after 6 weeks of treatment. Both lovastatin and pravastatin caused significant (P < .05 compared with placebo) decreases in total cholesterol (by 20.9 and 20.6%, respectively), LDL cholesterol (by 27.8 and 29.9%), and triglycerides (by 13.6 and 3.7%). Subjects' HDL increased by 2.3% with lovastatin (NS) and by 3.1% with pravastatin (P < .05). Lipoprotein(a) increased by 20.5% with lovastatin and by 1.1% with pravastatin; these changes were not significantly different from placebo. In patients with hypercholesterolemia, lovastatin and pravastatin have nearly identical effects on lipids and no significant effects on sleep and cognitive performance.