Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering

• Published in: The American Journal of Cardiology
• Main Authors: Pedersen, T R, Wilhelmsen, L, Faergeman, O, Strandberg, T E, Thorgeirsson, G, Troedsson, L, Kristianson, J, Berg, K, Cook, T J, Haghfelt, T, Kjekshus, J, Miettinen, T, Olsson, A G, Pyörälä, K, Wedel, H
• Other Authors: Aker Hospital, University of Oslo, Oslo, Norway. [e-mail]
• Format: Article in Journal/Newspaper
• Language: English
• Published: Excerpta Medica 2008
• Subjects: Adult; Aged; Anticholesteremic Agents; Cause of Death; Coronary Artery Disease; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Male; Middle Aged; Neoplasms; Risk; Scandinavia; Simvastatin; Survival Rate; Norway; Iceland
• Online Access: http://hdl.handle.net/2336/34612; https://doi.org/10.1016/S0002-9149(00)00910-3

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number ...