). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p<0.0001). Treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetic patients showed risk reductions for MCE and MVE (27% and 22%, respectively; p<0.0001) due to simvastatin treatment regardless of baseline A1C levels or obesity with the greatest effects seen for diabetic patients without CHD.
Figure 3: The Effects of Treatment with Simvastatin on Major Vascular Events and Major Coronary Events in HPS
N = number of patients in each subgroup. The inverted triangles are point estimates of the relative risk, with their 95% confidence intervals represented as a line. The area of a triangle is proportional to the number of patients with MVE or MCE in the subgroup relative to the number with MVE or MCE, respectively, in the entire study population. The vertical solid line represents a relative risk of one. The vertical dashed line represents the point estimate of relative risk in the entire study population.
Modifications of Lipid Profiles
Primary Hyperlipidemia (Fredrickson type lla and llb)
Simvastatin has been shown to be effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hyperlipidemia and in mixed hyperlipidemia. Maximal to near maximal response is generally achieved within 4-6 weeks and maintained during chronic therapy. Simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C (see Table 17).
Table 17: Mean Response in Patients with Primary Hyperlipidemia and Combined (mixed) Hyperlipidemia (Mean Percent Change from Baseline After 6 to 24 Weeks) TREATMENT N TOTAL-C LDL-C HDL-C TG*
*
median percent change
†
mean baseline LDL-C 244 mg/dL and median baseline TG 168 mg/dL
‡
mean baseline LDL-C 188 mg/dL and median baseline TG 128 mg/dL
§
mean baseline LDL-C 226 mg/dL and median baseline TG 156 mg/dL
¶
Study also included another treatment arm receiving a different dose of simvastatin; baseline mean LDL-C and median TG values were calculated across all treatment arms in study
#
mean baseline LDL-C 156 mg/dL and median baseline TG 391 mg/dL.
Lower Dose Comparative Study†
(Mean % Change at Week 6)
Simvastatin 5 mg q.p.m. 109 -19 -26 10 -12
Simvastatin 10 mg q.p.m. 110 -23 -30 12 -15
Scandinavian Simvastatin Survival Study‡
(Mean % Change at Week 6)
Placebo 2223 -1 -1 0 -2
Simvastatin 20 mg q.p.m. 2221 -28 -38 8 -19
Upper Dose Comparative Study§, ¶
(Mean % Change Averaged at Weeks 18 and 24) &nb
