Kobashigawa J A, Murphy F L, Stevenson L W, Moriguchi J D, Kawata N, Kamjoo P, Brownfield E, Wilmarth J, Leonard L, Chuck C
Division of Cardiology, UCLA School of Medicine 90024-1679.
Circulation. 1990 Nov;82(5 Suppl):IV281-3.
Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients.
高胆固醇血症在许多心脏移植患者中都会出现,它可能会加重移植冠状动脉病变,并导致外周血管疾病。洛伐他汀可抑制3-羟基-3-甲基戊二酰辅酶A还原酶,对于一般心脏患者群体,每天服用40 - 80毫克的剂量能有效降低胆固醇,但在心脏移植受者中,它与横纹肌溶解症有关。为了确定较低剂量的洛伐他汀对心脏移植后降低胆固醇是否有效且安全,44名在心脏移植至少6个月后血胆固醇高于200毫克/分升的患者每天服用10 - 20毫克洛伐他汀。此外,对6名患者检测了洛伐他汀酶抑制剂水平,以确定该药物的代谢是否异常。洛伐他汀使总胆固醇从282±54毫克/分升降至208±62毫克/分升,降幅达28%(p<0.005),主要是因为低密度脂蛋白组分降低,并且在44名患者中有43名耐受性良好,没有任何症状或肌酸磷酸激酶水平异常。当洛伐他汀剂量增至每天40毫克时,有1名患者出现了横纹肌溶解症和可逆性肾衰竭。6名移植患者的酶抑制剂水平比正常志愿者测得的水平高4.2 - 7.8倍。低剂量洛伐他汀能有效降低移植患者的胆固醇,但代谢可能因环孢素而改变。可能需要监测酶抑制剂水平,以便安全地给心脏移植受者使用这种药物。