Holdaas Hallvard, Fellström Bengt, Jardine Alan G, Nyberg Gudrun, Grönhagen-Riska Carola, Madsen Sören, Neumayer Hans-Hellmut, Cole Edward, Maes Bart, Ambühl Patrice, Logan John O, Staffler Beatrix, Gimpelewicz Claudio
Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway.
Nephrol Dial Transplant. 2005 May;20(5):974-80. doi: 10.1093/ndt/gfh735. Epub 2005 Mar 22.
Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy.
2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years).
In patients starting treatment with fluvastatin <4.5 years after renal transplantation, the incidence of cardiac events was 4.6% over 5.1 years vs 9.2% in those on placebo (P = 0.007). Fluvastatin significantly reduced the risk of cardiac death and non-fatal myocardial infarction by 56% [risk ratio (RR): 0.44; 95% confidence interval (95% CI): 0.26-0.74; P = 0.002]. In a more detailed analysis patients were grouped into 2-year intervals (since the last transplantation). The frequency of cardiac death and non-fatal myocardial infarction was reduced by 3.2%, 5.1%, 9.6% and 8.2% with fluvastatin treatment as compared to 6%, 10.4%, 13.4% and 9.6% with placebo when treatment was initiated at 0-2, 2-4, 4-6 and >6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (<47 months) fluvastatin use was associated with a risk reduction of 64% compared with 19% for patients in the fourth quartile (>120 months) (P = 0.033).
Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart disease.
肾移植受者的预期寿命显著缩短，主要是由于过早发生心血管疾病。本分析的目的是研究移植后开始治疗的时间对他汀类药物治疗益处的重要性。
2102名总胆固醇水平为4.0 - 9.0 mmol/l的肾移植受者被随机分配接受氟伐他汀治疗（n = 1050）或安慰剂治疗（n = 1052），并随访平均5.1年。终点为主要心脏事件。从移植到随机分组的平均中位时间为4.5年（范围：0.5 - 29年）。
在肾移植后<4.5年开始使用氟伐他汀治疗的患者中，5.1年内心脏事件的发生率为4.6%，而接受安慰剂治疗的患者为9.2%（P = 0.007）。氟伐他汀显著降低心脏死亡和非致命性心肌梗死的风险56% [风险比（RR）：0.44；95%置信区间（95%CI）：0.26 - 0.74；P = 0.002]。在更详细的分析中，患者按（自上次移植以来的）2年间隔分组。与安慰剂组相比，当在0 - 2年、2 - 4年、4 - 6年和>6年开始治疗时，氟伐他汀治疗组心脏死亡和非致命性心肌梗死的发生率分别降低了3.2%、5.1%、9.6%和8.2%，而安慰剂组分别为6%、10.4%、13.4%和9.6%。移植后0 - 2年开始使用氟伐他汀治疗的患者（与>6年开始治疗的患者相比）风险降低59%（RR：0.41；95%CI：0.18 - 0.92；P = 0.0328）。这也反映在肾脏替代治疗的总时间上：在第一个四分位数（<47个月）的患者中，使用氟伐他汀与风险降低64%相关，而在第四个四分位数（>120个月）的患者中为19%（P = 0.033）。
我们的数据支持在有过早发生冠心病高风险的移植受者人群中尽早引入氟伐他汀治疗。
