Hypertriglyceridemia (Fredrickson type lV)

The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 18.

Table 18: Six-Week, Lipid-Lowering Effects of Simvastatin in Type lV Hyperlipidemia Median Percent Change (25th and 75th percentile) from Baseline*  TREATMENT N Total-C LDL-C HDL-C TG VLDL-C Non-HDL-C
*
The median baseline values (mg/dL) for the patients in this study were: total-C = 254, LDL-C = 135, HDL-C = 36, TG = 404, VLDL-C = 83, and non-HDL-C = 215. 
Placebo 74 +2
(-7, +7)
 +1
(-8, +14)
 +3
(-3, +10)
 -9
(-25, +13)
 -7
(-25, +11)
 +1
(-9, +8)
 
Simvastatin 40 mg/day 74 -25
(-34, -19)
 -28
(-40, -17)
 +11
(+5, +23)
 -29
(-43, -16)
 -37
(-54, -23)
 -32
(-42, -23)
 

Dysbetalipoproteinemia (Fredrickson type lll)

The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 19.

Table 19: Six-Week, Lipid-Lowering Effects of Simvastatin in Type lll Hyperlipidemia Median Percent Change (min, max) from Baseline*  TREATMENT N Total-C LDL-C + IDL HDL-C TG VLDL-C + IDL Non-HDL-C
*
The median baseline values (mg/dL) were: total-C = 324, LDL-C = 121, HDL-C = 31, TG = 411, VLDL-C = 170, and non-HDL-C = 291. 
Placebo 7 -8
(-24, +34) -8
(-27, +23) -2
(-21, +16) +4
(-22, +90) -4
(-28, +78) -8
(-26, -39)
Simvastatin 40 mg/day 7 -50
(-66, -39) -50
(-60, -31) +7
(-8, +23) -41
(-74, -16) -58
(-90, -37) -57
(-72, -44)

Homozygous Familial Hypercholesterolemia

In a controlled clinical study, 4 patients, 19-27 years of age, with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses. Reductions in LDL-C were observed for all patients. The mean LDL-C reduction for the 40 mg dose was 14% (range 8% to 23%, median 12%).

Endocrine Function

In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the p