POSTTRANSPLANT HYPERLIPIDEMIA - LOW-DOSE LOVASTATIN LOWERS ATHEROGENIC LIPIDS WITHOUT PLASMA ACCUMULATION OF LOVASTATIN

Objectives. The purpose of the present study was twofold. First, to de termine the frequency of hyperlipidaemia after heart transplantation ( Tx) in relation to values obtained before Tx, Secondly, to examine the effect of low-dose lovastatin on possible antiatherogenic mechanisms and test the hypothesis that the side-effects are dose-dependent. Subj ects and design. Retrospective study of the frequency of hyperlipidaem ia disturbances in heart transplant patients. In addition, in a prospe ctive study, the safety and efficacy of incremental low doses of lovas tatin up to 20 mg day(-1) were studied, with measurements of its plasm a concentration in 24 cyclosporin A treated heart (n = 14) and kidney (n = 10) recipients with total cholesterol >7.5 mmol L-1. Results. Cho lesterol increased markedly after heart transplantation from a pretran splant value of 5.3 (5.0,5.6) mmol L-1 to 6.7 (6.4,7.0) mmolL(-1) afte r 1 year and then remained constant, but this increase was largely due to a 'normalization' since cholesterol decreased significantly during increasing heart failure before transplantation. Treatment with lovas tatin decreased total cholesterol by 19% (P < 0.001), primarily by an effect on LDL cholesterol. HDL cholesterol increased by 15% (P<0.05), whereas triglycerides remained unchanged. Lovastatin also caused a sig nificant reduction in apolipoprotein B of 16%, and lipid peroxidation of 40%, whereas apolipoprotein A-I, fibrinogen, and glycerol were unch anged. Plasma concentration of lovastatin was significantly higher in transplant recipients compared with controls, but there was no accumul ation during incremental dosing of lovastatin. The drug was well toler ated without significant symptoms or evidence of myopathy. Conclusions , Hyperlipidaemia is common after cardiac transplantation. Treatment w ith low dose lovastatin is well tolerated and has a favourable effect on atherogenic lipids.