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

• Published in: The Lancet (British edition) 2004-08, Vol.364 (9436), p.771-777
• Main Authors: Strandberg, Timo E, Pyörälä, Kalevi, Cook, Thomas J, Wilhelmsen, Lars, Faergeman, Ole, Thorgeirsson, Gudmundur, Pedersen, Terje R, Kjekshus, John
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticholesteremic Agents - therapeutic use; atorvastatin; average cholesterol levels; Biological and medical sciences; Cancer; cardiac outcomes; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Clinical trials; Coronary artery disease; Coronary Disease - blood; Coronary Disease - mortality; Coronary Disease - prevention & control; coronary-heart-disease; Dermatologi och venereologi; Dermatology and Venereal Diseases; Drugs; events; Fatalities; Follow-Up Studies; General aspects; Health risk assessment; Health risks; Heart diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Incidence; Male; Medical sciences; Middle Aged; Mortality; Motivation; Neoplasms - epidemiology; Neoplasms - mortality; Patients; placebo-controlled trial; pravastatin; prevention; Product safety; randomized controlled-trial; Scandinavian and Nordic Countries - epidemiology; Simvastatin; Simvastatin - adverse effects; Simvastatin - therapeutic use; Statins; Survival; Survival Rate; Therapy; Triglycerides
• ISSN: 0140-6736; 1474-547X
• 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.