心脏移植后从环孢素A转换为西罗莫司的患者中他汀类药物治疗的安全性和有效性。

Safety and efficacy of statin therapy in patients switched from cyclosporine a to sirolimus after cardiac transplantation.

作者信息

Aliabadi Arezu Z, Mahr Stephane, Dunkler Daniela, Grömmer Martina, Zimpfer Daniel, Wolner Ernst, Grimm Michael, Zuckermann Andreas O

机构信息

Department of Cardiothoracic Surgery, Medical University of Vienna, Währinger Gürtel, Vienna, Austria.

出版信息

Transplantation. 2008 Dec 27;86(12):1771-6. doi: 10.1097/TP.0b013e3181910eb2.

DOI:10.1097/TP.0b013e3181910eb2

PMID:19104420

Abstract

INTRODUCTION

Statins are an established therapy after cardiac transplantation. Sirolimus (Srl) has been used successfully in cardiac transplant patients. However, potential side effects are hyperlipidemia and interactions with statins. The aim of the study was to evaluate the safety and efficacy of statin therapy after switch to a Srl-based immunosuppression.

PATIENTS AND METHODS

Ninety-eight long-term patients were switched from Cyclosporine A to Srl. Also all patients received mycophenolate mofetil alone or mycophenolate mofetil plus steroid therapy. Reasons for switch were renal dysfunction, graftvasculopathy, or skin cancer. Patients were switched 7.8+/-4.7 years after transplant. Total observation period was 12 months before and after switch, respectively. Safety evaluation consisted of regular measurements of CPK and liver enzymes to evaluate the incidence myopathy and hepatoxicity. Efficacy analysis was performed by serial blood lipid assessments (low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides).

RESULTS

Forty-three percentage of patients received atorvastatin, 38% pravastatin, and 18% other drugs or therapy changes. Most lipid blood levels increased significantly after switch (cholesterol: 192.9+/-38.6 mg/dL vs. 221.8+/-49.2 mg/dL, P<0.0001; low-density lipoprotein: 108.0+/-35.6 mg/dL vs. 123.8+/-37.9 mg/dL, P<0.0001; and triglycerides: 178.3+/-88.2 mg/dL vs. 225.5+/-139.1 mg/dL, P<0.0001). Blood lipid levels after switch were not associated with statin type. Overall safety was acceptable, although incidence of myopathy doubled after switch (n=20 vs. 40; P<0.01). However, most cases were asymptomatic CPK elevations in the pravastatin group. Hepatotoxicity rate was 4% and only temporary.

CONCLUSION

Statin therapy after switch from cyclosporine A to Srl in long-term cardiac transplant patients is safe. However, regular testing of blood lipids and CPK should be mandatory.

摘要

引言

他汀类药物是心脏移植术后的一种既定治疗方法。西罗莫司（Srl）已成功应用于心脏移植患者。然而，其潜在副作用是高脂血症以及与他汀类药物的相互作用。本研究的目的是评估在转换为基于Srl的免疫抑制治疗后他汀类药物治疗的安全性和有效性。

患者与方法

98例长期患者从环孢素A转换为Srl。所有患者还单独接受霉酚酸酯或霉酚酸酯加类固醇治疗。转换的原因是肾功能不全、移植血管病变或皮肤癌。患者在移植后7.8±4.7年进行转换。转换前后的总观察期均为12个月。安全性评估包括定期测量肌酸磷酸激酶（CPK）和肝酶，以评估肌病和肝毒性的发生率。通过系列血脂评估（低密度脂蛋白、高密度脂蛋白、总胆固醇和甘油三酯）进行疗效分析。

结果

43%的患者接受阿托伐他汀，38%接受普伐他汀，18%接受其他药物或治疗改变。转换后大多数血脂水平显著升高（胆固醇：192.9±38.6mg/dL对221.8±49.2mg/dL，P<0.0001；低密度脂蛋白：108.0±35.6mg/dL对123.8±37.9mg/dL，P<0.0001；甘油三酯：178.3±88.2mg/dL对225.5±139.1mg/dL，P<0.0001）。转换后的血脂水平与他汀类药物类型无关。总体安全性是可接受的，尽管转换后肌病的发生率翻倍（n=20对40；P<0.01）。然而，大多数病例是普伐他汀组无症状的CPK升高。肝毒性发生率为4%，且只是暂时的。