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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2151-2156.)
© 1995 American Heart Association, Inc.

Articles

A Prospective, Randomized Trial of Phenytoin in Nonepileptic Subjects With Reduced HDL Cholesterol

Michael Miller; Rachel G. Burgan; Laura Osterlund; Jere P. Segrest; David W. Garber

From the University of Maryland Medical System, Baltimore (M.M., R.G.B.), and the University of Alabama at Birmingham (L.O., J.P.S., D.W.G.).

Correspondence to David W. Garber, PhD, University of Alabama at Birmingham, DREB Room 630, Birmingham, AL 35294-0012.

Abstract Observational studies have demonstrated a positive association between phenytoin use and HDL cholesterol (HDL-C). Our goal was to determine whether phenytoin raises HDL-C in nonepileptic subjects at risk for coronary artery disease. We performed a double-blind, placebo-controlled, parallel-group study in 41 subjects with reduced levels of HDL-C. Subjects were placed on an American Heart Association Step I diet and were randomized to receive either phenytoin or placebo for 3 months. Serum levels of phenytoin were monitored and adjusted to between 7.5 and 15 µg/mL. Fasting levels of lipids and lipoproteins were determined twice at baseline (weeks -2 and -1) and during the treatment phase of the study (weeks 11 and 12). Compared with dietary baseline, phenytoin-treated subjects experienced significant paired percent increases in total HDL-C (12.4%; P<.01), an effect confined to the HDL₂ subfraction (137%; P<.01). The paired percent increases in HDL-C and HDL₂ levels remained significant after adjustment for placebo (P<.05, P<.025, respectively). There were no significant differences in the paired percent changes from dietary baseline in total cholesterol, triglyceride, or LDL cholesterol levels between placebo and phenytoin-treated groups. The significant paired percent increases in total HDL-C and HDL₂ from dietary baseline suggest a potential role for phenytoin in subjects with reduced levels of HDL-C.

Key Words: cholesterol • phenytoin • humans • HDL

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