Lancet. 2004 Aug 28;364(9436):771-7 Strandberg TE， Pyorala K， Cook TJ， Wilhelmsen L， Faergeman O， Thorgeirsson G， Pedersen TR， Kjekshus J; 4S Group. Department of Medicine， University of Helsinki， Helsinki， PL 340， 00029 HUS， Finland. timo.strandberg@hus.fi
BACKGROUND: 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. METHODS: 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. FINDINGS: 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.
INTERPRETATION: 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.
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