Amlodipine Besylate and Atorvastatin Calcium (Page 10 of 13)

14.7 Atorvastatin for Hyperlipidemia and Mixed Dyslipidemia

Atorvastatin reduces total-C, LDL-C, very-low density lipoprotein cholesterol (VLDL-C), apo B, and TG, and increases HDL-C in patients with hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb). Therapeutic response is seen within 2 weeks, and maximum response is usually achieved within 4 weeks and maintained during chronic therapy.

Atorvastatin is effective in a wide variety of patient populations with hyperlipidemia, with and without hypertriglyceridemia, in men and women, and in the elderly.

In two multicenter, placebo-controlled, dose-response studies in patients with hyperlipidemia, atorvastatin given as a single dose over 6 weeks significantly reduced total-C, LDL-C, apo B, and TG. (Pooled results are provided in Table 10.)

Table 10. Dose Response in Patients with Primary Hyperlipidemia (Adjusted Mean % Change From Baseline)a

Dose N TC LDL-C Apo B TG HDL-C Non-HDL- C/HDL-C
Placebo 21 4 4 3 10 -3 7
10 22 -29 -39 -32 -19 6 -34
20 20 -33 -43 -35 -26 9 -41
40 21 -37 -50 -42 -29 6 -45
80 23 -45 -60 -50 -37 5 -53

a Results are pooled from 2 dose-response studies.

In patients with Fredrickson Types IIa and IIb hyperlipoproteinemia pooled from 24 controlled trials, the median (25th and 75th percentile) percent changes from baseline in HDL-C for atorvastatin 10, 20, 40, and 80 mg were 6.4 (-1.4, 14), 8.7 (0, 17), 7.8 (0, 16), and 5.1 (-2.7, 15), respectively. Additionally, analysis of the pooled data demonstrated consistent and significant decreases in total-C, LDL-C, TG, total-C/HDL-C, and LDL-C/HDL-C.

In three multicenter, double-blind studies in patients with hyperlipidemia, atorvastatin was compared to other statins. After randomization, patients were treated for 16 weeks with either atorvastatin 10 mg per day or a fixed dose of the comparative agent (Table 11).

Table 11. Mean Percentage Change from Baseline at Endpoint (Double-Blind, Randomized, Active-Controlled Trials)

Treatment(Daily Dose) N Total-C LDL-C Apo B TG HDL-C Non-HDL-C/HDL-C
Study 1
Atorvastatin 10 mg 707 -27a -36a -28a -17a +7 -37a
Lovastatin 20 mg 95% CI for Diff1 191 -19 -9.2, -6.5 -27 -10.7, -7.1 -20 -10, -6.5 -6 -15.2, -7.1 +7 -1.7, 2 -28 -11.1, -7.1
Study 2 Atorvastatin 10 mg 222 -25b -35b -27b -17b +6 -36b
Pravastatin 20 mg 95% CI for Diff1 77 -17 -10.8, -6.1 -23 -14.5, -8.2 -17 -13.4, -7.4 -9 -14.1, -0.7 +8 -4.9, 1.6 -28 -11.5, -4.1
Study 3
Atorvastatin 10 mg 132 -29c -37c -34c -23c +7 -39c
Simvastatin 10 mg 95% CI for Diff1 45 -24 -8.7, -2.7 -30 -10.1, -2.6 -30 -8, -1.1 -15 -15.1, -0.7 +7 -4.3, 3.9 -33 -9.6, -1.9

1 A negative value for the 95% CI for the difference between treatments favors atorvastatin for all except HDL-C, for which a positive value favors atorvastatin. If the range does not include 0, this indicates a statistically significant difference.

a Significantly different from lovastatin, ANCOVA, p ≤0.05

b Significantly different from pravastatin, ANCOVA, p ≤0.05

c Significantly different from simvastatin, ANCOVA, p ≤0.05

The impact on clinical outcomes of the differences in lipid-altering effects between treatments shown in Table 11 is not known. Table 11 does not contain data comparing the effects of atorvastatin 10 mg and higher doses of lovastatin, pravastatin, and simvastatin. The drugs compared in the studies summarized in the table are not necessarily interchangeable.

14.8 Atorvastatin for Hypertriglyceridemia

The response to atorvastatin in 64 patients with isolated hypertriglyceridemia (Fredrickson Type IV) treated across several clinical trials is shown in the table below (Table 12). For the atorvastatin-treated patients, median (min, max) baseline TG level was 565 (267–1502).

Table 12. Combined Patients with Isolated Elevated TG: Median (min, max) Percentage Change From Baseline

Placebo(N=12) Atorvastatin 10 mg (N=37) Atorvastatin 20 mg (N=13) Atorvastatin 80 mg(N=14)
TG -12.4 (-36.6, 82.7) -41 (-76.2, 49.4) -38.7 (-62.7, 29.5) -51.8 (-82.8, 41.3)
Total-C -2.3 (-15.5, 24.4) -28.2 (-44.9, -6.8) -34.9 (-49.6, -15.2) -44.4 (-63.5, -3.8)
LDL-C 3.6 (-31.3, 31.6) -26.5 (-57.7, 9.8) -30.4 (-53.9, 0.3) -40.5 (-60.6, -13.8)
HDL-C 3.8 (-18.6, 13.4) 13.8 (-9.7, 61.5) 11 (-3.2, 25.2) 7.5 (-10.8, 37.2)
VLDL-C -1 (-31.9, 53.2) -48.8 (-85.8, 57.3) -44.6 (-62.2, -10.8) -62 (-88.2, 37.6)
non-HDL-C -2.8 (-17.6, 30) -33 (-52.1, -13.3) -42.7 (-53.7, -17.4) -51.5 (-72.9, -4.3)

14.9 Atorvastatin for Dysbetalipoproteinemia

The results of an open-label crossover study of 16 patients (genotypes: 14 apo E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia (Fredrickson Type III) are shown in the table below (Table 13).

Table 13. Open-Label Crossover Study of 16 Patients with Dysbetalipoproteinemia ( Fredrickson Type III)

Median % Change (min, max)
Median (min, max) at Atorvastatin Atorvastatin
Baseline (mg/dL) 10 mg 80 mg
Total-C 442 (225, 1320) -37 (-85, 17) -58 (-90, -31)
TG 678 (273, 5990) -39 (-92, -8) -53 (-95, -30)
Intermediate-density lipoprotein cholesterol (IDL-C) + VLDL-C 215 (111, 613) -32 (-76, 9) -63 (-90, -8)
non-HDL-C 411 (218, 1272) -43 (-87, -19) -64 (-92, -36)

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