Post-transplant hyperlipidaemia : low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin

• Published in: Journal of internal medicine Vol. 242; no. 6; pp. 483 - 490
• Main Authors: GULLESTAD, L, NORDAL, K. P, FORFANG, K, IHLEN, H, HØSTMARK, A, BERG, K. J, CHENG, H, SCHWARTZ, M. S, GEIRAN, O, SIMONSEN, S
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Science 01.12.1997
• Subjects: Adult; Aged; Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - therapeutic use; Biological and medical sciences; Cholesterol - blood; Dose-Response Relationship, Drug; Female; General and cellular metabolism. Vitamins; Heart Transplantation; Humans; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Incidence; Lovastatin - administration & dosage; Lovastatin - adverse effects; Lovastatin - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Time Factors; Treatment Outcome; Human; Postoperative; Evaluation; Prevalence; Enzyme; Enzyme inhibitor; Cardiovascular disease; Metabolic diseases; Lipids; Lovastatin; Transplantation; Threshold dose; Retrospective; Prevention; Treatment; Surgery; Heart disease; Hydroxymethylglutaryl-CoA reductase; Hyperlipemia; Oxidoreductases; Dyslipemia; Antilipemic agent
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/j.1365-2796.1997.tb00021.x

The purpose of the present study was twofold. First, to determine 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. Retrospective study of the frequency of hyperlipidaemia disturbances in heart transplant patients. In addition, in a prospective study, the safety and efficacy of incremental low doses of lovastatin up to 20 mg day-1 were studied, with measurements of its plasma concentration in 24 cyclosporin A treated heart (n = 14) and kidney (n = 10) recipients with total cholesterol > 7.5 mmol L-1. Cholesterol increased markedly after heart transplantation from a pretransplant value of 5.3 (5.0,5.6) mmol L-1 to 6.7 (6.4,7.0) mmol L-1 after 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 lovastatin 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 significant reduction in apolipoprotein B of 16%, and lipid peroxidation of 40%, whereas apolipoprotein A-I, fibrinogen, and glycerol were unchanged. Plasma concentration of lovastatin was significantly higher in transplant recipients compared with controls, but there was no accumulation during incremental dosing of lovastatin. The drug was well tolerated without significant symptoms or evidence of myopathy. Hyperlipidaemia is common after cardiac transplantation. Treatment with low dose lovastatin is well tolerated and has a favourable effect on atherogenic lipids.