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

The Scandinavian Simvastatin Survival Study (4S) and other randomized clini cal trials have demonstrated that cholesterol-lowering treatment with stati ns improves prognosis in patients with coronary atherosclerosis compared wi th placebo. The effect of therapy with statins beyond the typical 5 to 6 ye ars' duration of the trials, in particular regarding the risk of cancer, ha s not been investigated. This study examines the long-term effects of simva statin for up to 8 years on cause-specific mortality in patients with coron ary heart disease (CHD). We performed an observational, government registry -based study of mortality in the groups originally randomized to simvastati n 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 surviv ing patients). Randomization took place at outpatient clinics at 94 clinica l centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 198 9. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. patients received treat ment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day a t 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or place bo. After the double-blind period, most patients in both treatment groups r eceived simvastatin as open-label prescription. Of the 1,967 patients origi nally 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 i nterval 0.60 to 0.82, p = 0.00002). The total number of cancer deaths was 6 8 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relat ive risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0.087), and the nu mbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in pa tients with CHD is safe and yields continued survival benefit. (C) 2000 by Excerpta Medico, Inc.