COMPARISON OF EFFECTS ON SLEEP OF LOVASTATIN AND PRAVASTATIN IN HYPERCHOLESTEROLEMIA

The effects on sleep of lovastatin, a 3-hydroxy-3-methylglutaryl coenz yme A reductase inhibitor administered as a lipophilic lactone prodrug , and pravastatin, an inhibitor administered in its active, hydrophili c, open-acid form, were compared by polysomnographic sleep monitoring. Twenty-four men with primary hypercholesterolaemia (low-density lipop rotein 4 to 7 mmol/liter) each received 2 of the following 3 treatment s in a randomized, incomplete block, crossover design study: lovastati n (40 mg/day), pravastatin (40 mg/day), and placebo. Test drug was adm inistered once daily for 4 weeks during each half of the crossover stu dy. Subjective sleep assessments were obtained throughout each treatme nt period, and polysomnographic recordings were obtained at the end of the 4-week treatment periods. Treatment periods were separated by a 1 -week washout. Lovastatin did not differ from placebo regarding any po lysomnographic parameter except ''number of entries to wake,'' for whi ch it produced fewer entries (i.e., change was in the direction of imp rovement). Pravastatin did not differ from placebo regarding any polys omnographic measures, but was associated with worsening in relation to lovastatin in the following parameters: sleep efficiency, entries to wake, percent rapid eye movement sleep, wake time during sleep, and to tal wake time. For each of these 4 parameters, although neither drug s howed marked differences from placebo, the mean change in the lovastat in group was in the direction of improved sleep, whereas the change in the pravastatin group was in the direction of disturbed sleep. Neithe r lovastatin nor pravastatin had any effect on subjective, qualitative sleep ratings. Treatment with lovastatin produced no deleterious effe cts on sleep after 4 weeks of treatment in men with primary hyperchole sterolemia; pravastatin was similarly without effect. Thus, the inhere nt lipophilicity of the closed lactone 3-hydroxy-3-methylglutaryl coen zyme A reductase inhibitor lovastatin did not produce any detectable c hanges in sleep in this patient cohort.