Management of hyperlipidaemia associated with heart transplantation.
The past 20 years have seen considerable advances in the field of organ transplantation that have together led to a notable increase in survival rates and a reduction in postoperative morbidity of transplant recipients. However, these advances have been accompanied by the appearance of other complications of transplantation, such as post-transplant hyperlipidaemia, hypertension and graft coronary vasculopathy (GCV). GCV is an accelerated form of atherosclerosis in transplanted hearts that has proven to be one of the most important late complications of heart transplantation and is the single most limiting factor for long-term survival. The most important factors favouring the development of hyperlipidaemia after heart transplantation are inappropriate diet in combination with reduced physical activity, adverse effects of immunosuppressive therapy (ciclosporin [cyclosporin], corticosteroids) and polygenic hypercholesterolaemia in combination with ischaemic cardiomyopathy. The treatment of hyperlipidaemia in heart transplant recipients results in a variety of complications and side effects. In particular, interactions between lipid-lowering drugs and immunosuppressive therapy have been observed. Early attempts at treatment with bile acid binding agents and nicotinic acid derivatives often proved insufficiently effective, and led to unacceptable adverse effects and significant disturbances of ciclosporin metabolism. Fibric acid derivatives provided moderate reductions in triglyceride and total cholesterol levels that were mostly--with the exception of gemfibrozil--accompanied by significant impairment of renal function. Probucol achieved only an unsatisfactory reduction in low-density lipoprotein (LDL) cholesterol. Omega-3 fatty acids lower cholesterol levels and improve endothelial function in heart transplant recipients; however, the significance of these effects is still under discussion. As in the general patient population, use of HMG-CoA reductase inhibitors (statins) achieved significant reductions in cholesterol levels. Use of these substances has resulted in significantly extended long-term survival times, significantly less GCV and fewer severe graft rejections. Selective cholesterol absorption inhibitors, administered with or without statins, could provide another treatment option for heart transplant patients with hypercholesterolaemia. In severe familial hypercholesterolaemia, which is rarely observed in heart transplant recipients, treatment with statins can be combined with extracorporeal cholesterol elimination procedures such as heparin induced extracorporeal LDL cholesterol precipitation (HELP). HELP enables total cholesterol levels to be kept within any desired target range, and has been used successfully and without adverse effects in heart transplant recipients.
Wenke
Klaus
K
Division of Cardiac Surgery, Hospital Munich-Bogenhausen, Munich, Germany. klaus.wenke@extern.lrz-muenchen.de
D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002352:Carrier Proteins / Q000494:pharmacology / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use; D016027:Heart Transplantation / Q000009:adverse effects*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000178:diet therapy* / Q000188:drug therapy* / Q000209:etiology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000924:Anticholesteremic Agents; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D015525:Fatty Acids, Omega-3; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; D006493:Heparin; D011341:Probucol