Jardine A, Holdaas H
Department of Medicine and Therapeutics, Western Infirmary, Glasgow, U.K.
J Clin Pharm Ther. 1999 Dec;24(6):397-408. doi: 10.1046/j.1365-2710.1999.00252.x.
Cardiovascular disease remains a significant cause of morbidity and mortality in patients who have undergone renal transplantation, with one of the main risk factors being post-transplantation hyperlipidaemia. To date, however, optimal management of elevated lipid levels in such patients has been hindered by the lack of both effective and safe treatments, coupled with concerns over probable interactions with immunosuppressive therapy, particularly cyclosporin. Numerous studies confirm that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, such as fluvastatin, are effective lipid-lowering agents in renal transplant recipients, supporting findings in other patients' groups. Moreover, based on investigations of metabolic profile and clinical observation, fluvastatin (at dosages of up to 80 mg/day) is well tolerated in renal transplant recipients receiving cyclosporin. In clinical trials to date, no instances of rhabdomyolysis have been observed during co-administration of fluvastatin and cyclosporin. The potential of fluvastatin for improving survival in renal transplant recipients, in terms of both cardiovascular mortality and graft rejection, is currently being investigated in two ongoing studies: ALERT (Assessment of Lescol [fluvastatin] in Renal Transplantation) and SOLAR (Study of Lescol [fluvastatin] in Acute Rejection). The results of these landmark studies should confirm the safe utility of fluvastatin in the renal transplantation setting.
心血管疾病仍然是肾移植患者发病和死亡的重要原因,主要危险因素之一是移植后高脂血症。然而,迄今为止,由于缺乏有效且安全的治疗方法,再加上对其与免疫抑制疗法(尤其是环孢素)可能存在相互作用的担忧,此类患者血脂升高的最佳管理受到了阻碍。大量研究证实,3-羟基-3-甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂,如氟伐他汀,在肾移植受者中是有效的降脂药物,这也佐证了在其他患者群体中的研究结果。此外,基于代谢特征研究和临床观察,氟伐他汀(剂量高达80毫克/天)在接受环孢素治疗的肾移植受者中耐受性良好。在迄今为止的临床试验中,氟伐他汀与环孢素联合使用期间未观察到横纹肌溶解的病例。目前正在进行两项研究:ALERT(肾移植中氟伐他汀[来适可]评估)和SOLAR(急性排斥反应中来适可[氟伐他汀]研究),以调查氟伐他汀在改善肾移植受者心血管死亡率和移植物排斥反应方面的生存潜力。这些具有里程碑意义的研究结果应能证实氟伐他汀在肾移植环境中的安全效用。