Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S)

Summary 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.