HD. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were eva luated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. ZOCOR significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.
Modifications of Lipid Profiles
Primary Hyperlipidemia (Fredrickson type lla and llb)
ZOCOR 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. ZOCOR significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; ZOCOR also decreased TG and increased HDL-C (see Table 5).
Table 5: 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 ¶ 21% and 36% median reduction in TG in patients with TG ≤200 mg/dL and TG >200 mg/dL, respectively. Patients with TG >350 mg/dL were excluded # mean baseline LDL-C 156 mg/dL and median baseline TG 391 mg/dL.
Lower Dose Comparative Study†
(Mean % Change at Week 6)
ZOCOR 5 mg q.p.m. 109 -19 -26 10 -12
ZOCOR 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
ZOCOR 20 mg q.p.m. 2221 -28 -38 8 -19
Upper Dose Comparative Study§
(Mean % Change Averaged at Weeks 18 and 24)
ZOCOR 40 mg q.p.m. 433 -31 -41 9 -18
ZOCOR 80 mg q.p.m.¶
664 -36 -47 8 -24
Multi-Center Combined Hyperlipidemia Study#
(Mean % Change at Week 6)
Placebo
125
1
2
3
-4
ZOCOR 40 mg q.p.m.
123 -25 -29 13 -28
ZOCOR 80 mg q.p.m. 124 -31 -36 16 -33
Hypertriglyceridemia (Fredrickson type IV)
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 6.
Table 6: 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)
ZOCOR 40 mg/day
74
-25
(-34, -19)
-28
(-40, -17)
&
