A COMPARATIVE-STUDY OF THE EFFICACY OF SIMVASTATIN AND GEMFIBROZIL INCOMBINED HYPERLIPOPROTEINEMIA - PREDICTION OF RESPONSE BY BASE-LINE LIPIDS, APO E GENOTYPE, LIPOPROTEIN(A) AND INSULIN

Combined hyperlipoproteineria (CHL) can be difficult to treat because of the heterogeneous nature of the lipoprotein abnormalities. We compa red the relative efficacies of simvastatin and gemfibrozil and sought predictors of responsiveness in terms of the baseline lipids and other potential metabolic determinants (plasma insulin, Lp(a) and apo E gen otype). Sixty-six subjects entered a cross-over, randomized trial invo lving 12 weeks on each drug. Efficacy was assessed after 6 and 12 week s on each treatment. Simvastatin lowered total cholesterol 24%, trigly cerides 12%, LDL cholesterol 33%, raised HDL cholesterol 13% and subst antially reduced the cholesterol:triglyceride ratio in VLDL and IDL. G emfibrozil lowered total cholesterol 5%, triglycerides 44%, raised HDL 26% and reduced VLDL and IDL lipids more than simvastatin did. LDL si ze increased with both treatments and HDL size increased with simvasta tin. Responsiveness (25% fall in cholesterol or 40% fall in triglyceri des) was shown by 31/61 subjects when taking simvastatin (cholesterol- lowering) and by 44/60 taking gemfibrozil (triglyceride-lowering). Res ponsiveness was greatest in those with apo E, genotype with both drugs (P < 0.05). Unexpectedly, responders to simvastatin tended to have lo wer baseline total cholesterol but higher triglyceride levels than tho se whose cholesterol or triglyceride was lowered by gemfibrozil. Never theless, more hypercholesterolemic subjects responded to simvastatin a nd more hypertriglyceridemic subjects to gemibrozil. Lp(a) (P = 0.04) and plasma insulin concentrations (P = 0.03) were negative predictors of percentage triglyceride-lowering with gemfibrozil. The difference b etween the two drugs in triglyceride-lowering lessened with rising ins ulin and falling HDL cholesterol. Thus, the responsiveness to the two major classes of lipid lowering drugs can be partly predicted from bas eline lipids and related metabolic parameters. (C) 1997 Elsevier Scien ce Ireland Ltd.