Strandberg Timo E, Pyörälä Kalevi, Cook Thomas J, Wilhelmsen Lars, Faergeman Ole, Thorgeirsson Gudmundur, Pedersen Terje R, Kjekshus John
Department of Medicine, University of Helsinki, Helsinki, PL 340, 00029 HUS, Finland.
Lancet. 2004;364(9436):771-7. doi: 10.1016/S0140-6736(04)16936-5.
The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5-6-year trial periods are unknown. We extended post-trial follow-up of participants in the Scandinavian Simvastatin Survival Study (4S) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial.
4S was a randomised double-blind trial of simvastatin or placebo in patients with coronary heart disease, serum total cholesterol 5.5-8.0 mmol/L, and serum triglycerides 2.5 mmol/L or lower. The double-blind period lasted for a median of 5.4 years (range for survivors 4.9-6.3) and ended in 1994. After the trial, most patients in both groups received open-label lipid-lowering treatment. National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years (range for survivors 9.9-11.3). Analysis was by intention to treat.
414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up (relative risk 0.85 [95% CI 0.74-0.97], p=0.02), a difference largely attributable to lower coronary mortality in the simvastatin group (238 vs 300 deaths; 0.76 [0.64-0.90], p=0.0018). 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group (0.81 [0.60-1.08], p=0.14), and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group (0.88 [0.73-1.05], p=0.15). Incidence of any specific type of cancer did not rise in the simvastatin group.
Simvastatin treatment for 5 years in a placebo-controlled trial, followed by open-label statin therapy, was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only. No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group.
他汀类药物降低胆固醇治疗对超出常规5 - 6年试验期的死亡率和癌症风险的影响尚不清楚。我们对斯堪的纳维亚辛伐他汀生存研究（4S）的参与者进行了试验后随访，以调查试验结束5年后特定病因死亡率和癌症发病率。
4S是一项针对冠心病患者、血清总胆固醇5.5 - 8.0 mmol/L且血清甘油三酯2.5 mmol/L或更低的患者进行的随机双盲试验，比较辛伐他汀与安慰剂。双盲期持续时间中位数为5.4年（幸存者范围4.9 - 6.3年），于1994年结束。试验结束后，两组中的大多数患者接受了开放标签的降脂治疗。利用国家登记册评估原治疗组的死亡率、死亡原因和癌症发病率，总随访时间中位数为10.4年（幸存者范围9.9 - 11.3年）。分析采用意向性治疗。
在10.4年的随访期内，最初分配接受辛伐他汀治疗的414例患者和分配接受安慰剂治疗的468例患者死亡（相对风险0.85 [95%可信区间0.74 - 0.97]，p = 0.02），这一差异主要归因于辛伐他汀组较低的冠心病死亡率（238例死亡 vs 300例死亡；0.76 [0.64 - 0.90]，p = 0.0018）。辛伐他汀组有85例癌症死亡，安慰剂组有100例（0.81 [0.60 - 1.08]，p = 0.14），辛伐他汀组报告227例新发癌症，安慰剂组报告248例（0.88 [0.73 - 1.05]，p = 0.15）。辛伐他汀组任何特定类型癌症的发病率均未升高。
在安慰剂对照试验中接受5年辛伐他汀治疗，随后接受开放标签他汀治疗，与仅在过去5年接受开放标签他汀治疗相比，在10年随访期内具有生存获益。原辛伐他汀组和安慰剂组在癌症死亡率和发病率方面未发现差异。
