Lipoprotein Changes and Reduction in the Incidence of Major Coronary Heart Disease Events in the Scandinavian Simvastatin Survival Study (4S)

Abstract

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 Յ2.5 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 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, PϽ.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. Methods and Results-The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; PϽ.00001). Conclusions-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 guidelines that emphasize aggressive reduction of this lipid in CHD patients.

Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice

“…Weight loss data were extracted separately for the 'last-observation-carried-forward' method of analysis, which documents weight loss for all subjects regardless of when they leave the study, and for the 'study-completers' method of analysis, which documents weight loss only for subjects who completed follow-up. (2) Effects on cardiovascular risk factors: we assessed the effect of weight loss on change in cardiovascular risk factor levels, from baseline to the end of follow-up, for five risk factors that are considered clinically important: [39][40][41] (i) low-density lipoprotein (LDL) cholesterol; (ii) high-density lipoprotein (HDL) cholesterol; (iii) triglycerides; (iv) fasting blood glucose; (v) systolic and diastolic blood pressure. (3) Applicability to clinical practice: we assessed four study design criteria that we considered relevant to the applicability of findings to clinical practice: (i) duration of study; (ii) proportion of subjects lost to follow-up; (iii) appropriate control or 'usual care' group; and (iv) weight loss effects on cardiovascular risk factors in high-risk groups.…”

Lower is better: Implications of the Treating to New Targets (TNT) study for Canadian patients

“…The Incremental Decrease in End points through Agressive Lipid lowering (IDEAL) study (21) compared the outcomes of treatment of atorvastatin 80 mg with simvastatin 20 mg to 40 mg (the same dose as used in the 4S study [11]) among 8888 patients with a history of MI. The primary combined end point of coronary death, nonfatal MI and survival from cardiac arrest was reduced 11% in the atorvastatin group compared with that of the simvastatin group; however, the difference for this combined end point did not achieve statistical significance (P=0.07).…”

“…The benefits of lowering LDL-C levels are seen in a wide range of individuals with and without known CAD, in older and diabetic patients, following myocardial infarction (MI) and among different racial groups. The Scandinavian Simvastatin Survival Study (4S) (4,11) showed that patients within the lowest tertile of LDL-C levels, between 1.5 mmol/L and 2.7 mmol/L, had the lowest coronary event rates. Analysis of the Heart Protection Study (HPS) (6) showed that the reduction in CV end points achieved with simvastatin 40 mg daily in patients with a baseline LDL-C of less than 2.6 mmol/L was similar to that in patients with higher LDL-C levels.…”

Effects of simvastatin, an HMG‐CoA reductase inhibitor, in patients with hypertriglyceridemia

“…[1][2][3] However, few studies have investigated the efficacy of statins in patient populations with hypertriglyceridemia. This is, in part, due to the fact that low-density lipoprotein cholesterol (LDL-C) is considered to be the principal treatment target of this class of drugs and because, until recently, the evidence implicating triglycerides (TG) as an independent risk factor for coronary heart disease (CHD) was equivocal.…”