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Effects of ketoconazole on plasma lipids and lipoprotein(a) in familial hypercholesterolaemia, compared with
A F Stalenhoef1, P M Stuyt, J de Graaf
1Department of Medicine, University Hospital Nijmegen, The Netherlands. A.Stalenhoef@aig.azn.nl
Background:
Ketoconazole is an imidazole derivative that is active as a broad-spectrum antifungal agent. It is also an inhibitor of cholesterol production both in vivo and in vitro.
Methods:
We compared the effect of low-dose ketoconazole (200 mg/day) or simvastatin (20-40 mg/day) on lipids, lipoproteins and lipoprotein(a) [Lp(a)] in 10 patients with familial hypercholesterolaemia.
Results:
Ketoconazole reduced serum total cholesterol and low-density lipoprotein (LDL)-cholesterol by 7.6 and 9.7%, respectively. Simvastatin was more effective, the respective changes being -34.4 and -40.6%. Serum triglycerides and high-density lipoprotein (HDL) were unchanged by ketoconazole therapy, whereas simvastatin decreased triglyceride levels by 33.8% and increased HDL-cholesterol levels by 8.7%. Median Lp(a) levels tended to increase during simvastatin and to decrease during ketoconazole therapy. However, due to the wide range of baseline concentrations of Lp(a), these changes were not significant.
Conclusions:
Ketoconazole has some hypocholesterolaemic potential, but the effect of simvastatin is much more pronounced. The increase in Lp(a) during simvastatin therapy has been reported earlier, whereas ketoconazole does not exhibit an effect on the level of Lp(a).