Cardiovascular Center Cardiology, Heart Failure/Transplantation Clinic, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Circulation. 2012 Jul 24;126(4):440-7. doi: 10.1161/CIRCULATIONAHA.111.081059. Epub 2012 Jul 3.
Although newer immunosuppressive agents, such as mTOR (mammalian target of rapamycin) inhibitors, have lowered the occurrence of malignancies after transplantation, cancer is still a leading cause of death late after heart transplantation. Statins may have an impact on clinical outcomes beyond their lipid-lowering effects. The aim of the present study was to delineate whether statin therapy has an impact on cancer risk and total mortality after heart transplantation.
A total of 255 patients who underwent heart transplantation at the University Hospital Zurich between 1985 and 2007 and survived the first year were included in the present study. The primary outcome measure was the occurrence of any malignancy; the secondary end point was overall survival. During follow-up, a malignancy was diagnosed in 108 patients (42%). The cumulative incidence of tumors 8 years after transplantation was reduced in patients receiving a statin (34% versus 13%; 95% confidence interval, 0.25-0.43 versus 0.07-0.18; P<0.003). Statin use was associated with improved cancer-free and overall survival (both P<0.0001). A Cox regression model that analyzed the time to tumor formation with or without statin therapy, adjusted for age, male sex, type of cardiomyopathy, and immunosuppressive therapy (including switch to mTOR inhibitors or tacrolimus), demonstrated a superior survival in the statin group. Statins reduced the hazard of occurrence of any malignancy by 67% (hazard ratio, 0.33; 95% confidence interval, 0.21-0.51; P<0.0001).
Although it is not possible to adjust for all potential confounders because of the very long follow-up period, this registry suggests that statin use is associated with improved cancer-free and overall survival after cardiac transplantation. These data will need to be confirmed in a prospective trial.
虽然新型免疫抑制剂,如 mTOR(哺乳动物雷帕霉素靶蛋白)抑制剂,降低了移植后恶性肿瘤的发生,但癌症仍然是心脏移植后晚期死亡的主要原因。他汀类药物除了降脂作用外,可能对临床结果有影响。本研究旨在探讨他汀类药物治疗是否会影响心脏移植后癌症风险和总死亡率。
本研究共纳入了 1985 年至 2007 年期间在苏黎世大学医院接受心脏移植且存活至术后 1 年的 255 例患者。主要终点为任何恶性肿瘤的发生;次要终点为总生存率。随访期间,108 例患者(42%)诊断出恶性肿瘤。接受他汀类药物治疗的患者 8 年后肿瘤累积发生率降低(34%比 13%;95%置信区间,0.25-0.43 比 0.07-0.18;P<0.003)。他汀类药物的使用与癌症无进展和总生存率的提高相关(均 P<0.0001)。在分析有无他汀类药物治疗时肿瘤形成时间的 Cox 回归模型中,校正年龄、男性、心肌病类型和免疫抑制治疗(包括转换为 mTOR 抑制剂或他克莫司)后,他汀类药物组的生存情况更好。他汀类药物降低了 67%的恶性肿瘤发生风险(风险比,0.33;95%置信区间,0.21-0.51;P<0.0001)。
尽管由于随访时间非常长,无法调整所有潜在的混杂因素,但本注册研究表明,他汀类药物的使用与心脏移植后癌症无进展和总生存率的提高相关。这些数据需要在前瞻性试验中得到证实。