LIPOPROTEIN CHANGES AND REDUCTION IN THE INCIDENCE OF MAJOR CORONARY HEART-DISEASE EVENTS IN THE SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY

Background-The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides less than or equal to 2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patien ts in the placebo group and 431 (19%) of the 2221 patients in the simv astatin group (34% risk reduction, P<.00001). Simvastatin produced sub stantial changes in several lipoprotein components, which we have atte mpted to relate to the beneficial effects observed. Methods and Result s-The Cox proportional hazards model was used to assess the relationsh ip between lipid values (baseline, year 1, and percent change from bas eline at year 1) and MCEs. The reduction in MCEs within the simvastati n group was highly correlated with on-treatment levels and changes fro m baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with trigly cerides. We estimate that each additional 1% reduction in LDL choleste rol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). Conclus ions-These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current g uidelines that emphasize aggressive reduction of this lipid in CHD pat ients.