Professional Documents
Culture Documents
6 week, randomised, open-label, parallel-group, fixed-dose treatment 2268 adults with primary hypercholesterolaemia Randomised to 14 groups rosuvastatin 10, 20, 40 mg atorvastatin 10, 20, 40 or 80 mg simvastatin 10, 20, 40 or 80 mg pravastatin 10, 20 or 40 mg
Atorvastatin Rosuvastatin
10 mg 20 mg 40 mg 80 mg 10 mg 20 mg 40 mg
Simvastatin Rosuvastatin
10 mg 20 mg 40 mg 80 mg 10 mg 20 mg 40 mg
Pravastatin
10 mg 20 mg
40 mg
30
40 50 60
n=485 X
X n=648
*
n=473
n=634
*p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; pravastatin 10, 20, 40 mg p<0.002 vs atorvastatin 20, 40 mg; simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80 mg; pravastatin 40 mg
Adapted from Jones PH et al. Am J Cardiol 2003;92:152160
Rosuvastatin Slide Kit May 2004 [3]
10 mg * 10 mg 20 mg 40 mg
20 mg 80 mg
40 mg
10 mg
20 mg
40 mg
80 mg
10 mg
20 mg
40 mg
Rosuvastatin 10 mg (46%)
*p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; pravastatin 10, 20, 40 mg p<0.002 vs atorvastatin 20, 40 mg; simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80 mg; pravastatin 40 mg
Adapted from Jones PH et al. Am J Cardiol 2003;92:152160
Rosuvastatin Slide Kit May 2004 [4]
8 weeks
MERCURY I Schuster
n=539 n=539 n=529
0
Change in LDL-C from baseline (%)
Olsson
n=132 n=132 n=139 n=139
Blasetto
n=389 n=389 n=393 n=393
36 47
10 20 30
37
37
35
35 39
40 50 60
46
43
47
47
50
*p<0.001 vs atorvastatin
Jones PH et al. Am J Cardiol 2003;92:152160 Schuster H et al. Am Heart J 2004; 147: 705-712 Davidson M et al. Am J Cardiol 2002;89:26875 Schwartz G et al. Am Heart J 2004: In Press Olsson AG et al. Am Heart J 2002;144:104451 Blasetto JW et al. Am J Cardiol 2003;91(Suppl):3C10C
Rosuvastatin 10 mg Atorvastatin 10 mg
8 weeks Franken
n=128 n=131
Jukema
n=230 n=231
MERCURY I Schuster
n=539 n=925
-20
-30
-38 -41 -46 * -47 ** Rosuvastatin 10 mg Atorvastatin 20 mg
-40
-46 ns
-43
-44 *
-44
-50
Rosuvastatin 10 mg vs atorvastatin 10 and 20 mg; patients achieving 2003 European LDL-C goals
# 77%
80% 60%
*
67% 57% 66%
*
52%
36%
40% 20%
13%
0%
n=389 n=393
n=201 n=196
All patients
8 weeks MERCURY I Schuster1
All patients
LDL-C
<3mmol/l (115mg/dl) in general; <2.5mmol/l (97mg/dl) for patients with clinically established CVD or type 2 diabetes
Rosuvastatin Slide Kit May 2004 [7]
1. Schuster H & Fox J. Exp Opin Pharmacother 2004;5:1187-1200 2. Kritharides L. Eur Heart J Suppl 2004; 6(Suppl A): A12-A18
80%
#
77%
*
74%
60%
49% 38%
*
55%
40%
37%
12%
20mg 10mg
20%
10mg 20mg
40mg
10mg
20mg
11%
20mg
3%
n=74
0%
All patients Patients with CVD or 12 weeks type 2 diabetes Pooled data Kritharides2 <3mmol/l (115mg/dl) in general; <2.5mmol/l (97mg/dl) for patients with clinically established CVD or type 2 diabetes
Rosuvastatin Slide Kit May 2004 [8]
1. Schuster H & Fox J. Exp Opin Pharmacother 2004;5:1187-1200 2. Kritharides L. Eur Heart J Suppl 2004; 6(Suppl A): A12-A18
Rosuvastatin versus other statins Achievement of LDL-C Goals Across Dose Range
Patients achieving 2003 European LDL-C goals
100% Patients achieving 2003 European LDL-C goal (%)
LDL-C
*
69%
87% 83%
<3mmol/l (115mg/dl) in general; <2.5mmol/l (97mg/dl) for patients with clinically established CVD or type 2 diabetes
80%
72%
75% 66%
60%
40%
n=925
36%
n=189
20%
20%
22% 12% 3%
0%
10 20 40
10 20 40 80
10 20 40 80
10 20 40
Dose (mg)
*p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; pravastatin 10, 20, 40 mg p<0.002 vs atorvastatin 20 mg; simvastatin 20, 40 mg; pravastatin 20, 40 mg #p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80 mg; pravastatin 40 mg
Kritharides L. Eur Heart J Suppl 2004; 6(Suppl A): A12-A18
Rosuvastatin Slide Kit May 2004 [9]
*
40 mg 20 mg 80 mg 40 mg 20 mg
10 mg
10 mg
82%
96%
59%
87%
20
10 0
n=106 n=116
Rosuvastatin
Atorvastatin
*p=0.006 rosuvastatin 1040 mg vs atorvastatin 1080 mg Olsson AG et al. Am Heart J 2002;144:104451 Schuster H. Cardiology 2003;99:126139
100 Patients achieving 2003 European LDL-C goal by dose (%) 90 80 70 90% 83% 78%
*
40 mg 20 mg
18 weeks 12 weeks
80 mg 40 mg
60
50 40 30
10 mg
6 weeks
20 mg
20
10 0
n=131 n=132
Rosuvastatin
Atorvastatin
*p=0.05 rosuvastatin 40mg vs atorvastatin 80 mg patients with type 2 diabetes and dyslipidaemia Adapted from Franken A, Atherosclerosis Supplements 2004; 5 (1): 118 Abs M.513
Rosuvastatin Slide Kit May 2004 [11]
12
Change in HD-C from baseline (%)
* ns
n=473
Rosuvastatin Atorvastatin
10 8 6 4 2 0
n=634
10
20
40
80
8 6 4 2
5.6
10 20 40
10 20 40 80
10 20 40 80
10 20 40
Dose (mg)
*p<0.002 vs pravastatin 10 mg p<0.002 vs atorvastatin 20, 40, 80 mg; simvastatin 40 mg; pravastatin 20, 40 mg p<0.002 vs atorvastatin 40, 80 mg; simvastatin 40 mg; pravastatin 40 mg Observed data in ITT population
Adapted from Jones PH et al. Am J Cardiol 2003;92:152160
Rosuvastatin Slide Kit May 2004 [13]
10 20 40
10 20 40 80
10 20 40 80
10 20 40
13.2
20.0
22.6
23.7
26.1
26.8 28.2
*p<0.002 vs pravastatin 10, 20 mg p<0.002 vs simvastatin 40 mg; pravastatin 20, 40 mg p<0.002 vs simvastatin 40 mg; pravastatin 40 mg Adapted from Jones PH et al. Am J Cardiol 2003;92:152160
Rosuvastatin Slide Kit May 2004 [14]
Rosuvastatin 10 mg enables significantly more patients to achieve their LDL-C goal than the most commonly prescribed doses of other currently marketed statins, thereby reducing the need to titrate to higher doses
Rosuvastatin produces a significant increase in HDL-C which, unlike atorvastatin, is maintained across the dose range
Similar number of adverse events leading to withdrawal (<3%) as other currently marketed statins
6
Patients (%) 5 4 3 2 1
2.9%
1040 mg
3.2% 2.5%
1080 mg 1080 mg
2.5%
1040 mg
0
rosuvastatin
(n=3074)
atorvastatin
(n=2899)
simvastatin
(n=1457)
pravastatin
(n=1278)
3.0
Occurrence of ALT >3ULN (%)
50
60
70
50
60
70
Normal Blood
Glomerulus
Tubule
Bladder
Waste Products High molecular weight proteins (includes large amounts of albumin) Low molecular weight proteins (includes small amounts of albumin)
Rosuvastatin Slide Kit May 2004 [25]
Treatment
Placebo Rosuvastatin
n
330 1008 872 1850 628 438 63 342 452 314 325 162 64
Patients (%)
0.6 0.6 0.7 1.2 0.5 0.5 0 0.3 1.1 0.3 0 0.6 0
*dipstick positive proteinuria defined as a shift from no protein or trace at baseline to ++ assessed using derived GFR measurements
Vidt DG et al. Cardiology 2004;102:52-60 Please refer to local Prescribing Information
Rosuvastatin Slide Kit May 2004 [28]
72 71 70 69 68 67 66 65 64 63
70 68 67 66
67 n=371
(placebo)
Rosuvastatin Tolerability and Safety Maintenance of Renal Function in Different Patient Groups
Change in GFR in patients receiving long-term (>96 weeks) with rosuvastatin 10 mg 6 Mean change in GFR (ml/min/1.73m2) 5 4 3 2
n=590
n=413 n=650 n=243 n=356 n=537 n=480 n=303 n=832 n=836
n=61
Gender
Hypertension
Type 2 diabetes
n=46
Renal function was maintained or tended to improve slightly with long-term treatment
*dipstick positive proteinuria defined as a shift from no protein or trace at baseline to ++
Rosuvastatin Slide Kit May 2004 [31]
Low incidence of myopathy and of clinically significant increases in serum transaminases with rosuvastatin 1040 mg, comparable with currently marketed statins Renal function was maintained or tended to improve slightly with long-term treatment
As of end April 2004 Rosuvastatin is approved in over 50 countries >4 million prescriptions issued
Atorvastatin
Yes Yes Primarily hepatic No Yes 14 14
Simvastatin
Yes Yes Dual renal / hepatic No Yes <5 1.9
Pravastatin
No No Dual renal / hepatic Yes Yes 17 77
*Elimination T1/2 of drug and metabolites, if any. CRESTOR (rosuvastatin calcium) Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2003. Atorvastatin Calcium Prescribing Information 2002, Pfizer Inc, NY, NY; Simvastatin Prescribing Information, Merck & Co., Inc., Whitehouse Station, NJ; Pravastatin Prescribing Information 2003, Bristol-Meyers Squibb Company, Princeton, NJ.
Designed to help physicians to improve the management of patients with hypercholesterolaemia and others with or at risk of cardiovascular disease
Schuster H & Fox J. Expert Opinion in Pharmacotherapy 2004;5:1187-1200
CORONA
JUPITER
GISSI-HF
1. Schuster H & Fox J. Exp Opin Pharmacother 2004;5:1187-1200 2. Fellstrm B et al. Nephrol Dial Transplant 2003;18(Suppl 4):713 3. Ridker P. Circulation 2003;108:22922297