ROSUV E S astatin Evaluation program for stablishing fficacy

ROSUVastatin Evaluation program for Establishing Efficacy
and Safety in Indian Hyperlipidemia Patients
A prospective, open-label, multi-center, post-marketing study to evaluate the lipid altering efficacy and safety of
dose ranges of rosuvastatin in Indian hyperlipidemia patients in routine clinical practice
1
2
Navneet Wadhwa , Bhavesh Kotak , Chetan P. Shah
•
•
•
3
et al on behalf of the ROSUVEES study group
Clinical Pharmacologist & Medical Advisor, Ranbaxy Laboratories Ltd, Mumbai, India
Director - Medical, Regulatory and Pharmacovigilance, Ranbaxy Laboratories Ltd, Mumbai
Cardiologist at Heart Rhythm Clinic, Mumbai, India and Principal Investigator ROSUVEES study group
ROSUVEES study group investigators- Delhi (Pankaj Aneja, Anil Gupta, Raman Abhi, Rajeev Bansal); Mumbai (Chetan Shah, Jagdish Gotur, Dayanand Kumbla, Subhash Sonawala, Anil G Balani); Chennai (R Kedarnathan, P.
Chinnaiyan, S. Murthy, Asha Moorthy)
Correspondence: navneet.wadhwa@ranbaxy.com
Results - Primary Endpoints
Background
< Reducing LDL-C is associated with decreased risk for major cardiovascular events
Changes in Lipid Ratios over 8 weeks
1-3
< This is important considering ethnic diversity of Indian patient population with higher
LDL -C : HDL -C ratio
incidence of premature cardiovascular death
< Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor
is the most efficacious lipid-lowering agent of the statin class
5 mg
10 mg
20 mg
26.6% reduction
35.2% reduction
41.7% reduction

Baseline
3.62 ± 0.67
4.07 ± 0.86
4.32 ± 0.94

Week 8
2.66 ± 0.75
2.64 ± 0.87
2.52 ± 0.77
19.1% reduction
29.6% reduction
37% reduction
4
TC : HDL -C ratio
< Rosuvastatin monotherapy has been shown to have superior efficacy in reducing LDL-C

Baseline
5.02 ± 0.8
5.76 ± 1.13
6.17 ± 1.44
across its licensed dose ranges. In the dose ranges of 5 40 mg, rosuvastatin produces
5
mean reductions in plasma LDL-C of 45–63% and attains LDL-C goals in 48–89% of patients

Week 8
4.07 ± 0.87
4.06 ± 1.09
3.89 ± 0.84
< Most studies investigating the benefits of rosuvastatin and its different starting doses have
focused on Western and other Asian populations
Significant improvements in the TC:HDL-C and LDL-C:HDL-C ratios were noted after 8 weeks
of rosuvastatin treatment in all the dose-groups with the greatest magnitude effect in those
assigned to 20 mg
< ROSUVEES is the first Indian study to compare effectiveness & safety of three commonly used
doses (5 mg, 10 mg, and 20 mg) of rosuvastatin in hyperlipidemia
Secondary Endpoints
–
Proportion of patients achieving LDL-C
(ITT population by as-allocated dose)
Methods
100
% of patients attaining LDL-C target
patients, for 8 weeks
< Eligibilty:
o
o
Hyperlipidemia defined as fasting LDL -C >130 mg/dL who require lipid altering therapy
as judged by the treating physician
< Patients who met the entry criteria were allocated to the rosuvastatin start dose of 5mg, 10
mg or 20 mg based on the treating physician judgment considering the baseline LDLCholesterol levels, future cardiovascular risk, potential risk for adverse reactions, and
recommendations in the package insert
< In total 3 visits: baseline, week 4, week 8
< Dietary and therapeutic lifestyle changes advice was given to all patients assigned to
Rosuvastatin therapy.
and triglycerides
lipid goals
Mean % LDL- C reduction and Triglycerides after 8 weeks
% Reduction in TGs
Triglycerides (mg/dl)
-15
-20
-25
-30
-35
-40
279.6
-21.73%
250
-26.71
-35.89
172.7
150
-11.47%
143.8
-41.14
-45
Significant Reduction in LDL-C with
Rosuvastatin 10 mg and 20 mg Vs 5 mg
LDL –C: Mean reductions were 40.27 mg/dL, 60.73 mg/dL and 76.51 mg/dL, in the
5 mg, 10 mg, 20 mg dose respectively
<
TGs: The 20 mg dose group showed additional 16.49% mean percentage
reduction as compared to 10 mg group
60
50
50
40
30
12.5
20
10
0
0-1 risk factor
2+ risk factor
CHD/CHD equivalant
Overall population
0-1 risk factor
2+ risk factor
CHD/CHD equivalant
Risk groups
Validates usefulness of rosuvastatin in routine clinical practice in
achieving non-HDL cholesterol targets (82.19% patients
attained goal)
When significant triglyceride reduction is required from baseline (20-40%), the preferred
starting dose can be either rosuvastatin 10 mg or 20 mg
<
Validated the usefulness of rosuvastatin in routine clinical practice in achieving non-HDL
cholesterol targets (82.19% subjects attained goal) and reducing atherogenic risk profile
of Indian hyperlipidemic patients.
<
Rosuvastatin is an effective therapy for reducing LDL-C, improving atherogenic lipid
profile & facilitating achievement of lipid goals in Indian pts.
<
The safety results confirmed that rosuvastatin is safe and tolerable in Indian patients
with no significant differences in side effects than those reported in published literature
from other geographies
<
ROSUVEES study established rosuvastatin as an effective therapy for reducing LDL-C,
improving atherogenic lipid profile, and facilitating achievement of lipid goals in Indian
patients with hyperlipidemia
<
The practice recommendations from the results imply that in the Indian population,
rosuvastatin 10 mg or 20 mg as starting could be a preferred dose across the risk
categories without any concerns of exaggerated clinical response or major safety issues
and achieve significant reductions in LDL-C and TGs, and high rates of lipid goals
attainment
<
Especially, in the CHD/CHD equivalent population, and in those with more cardiovascular
risk factors, the 5 mg dose may be inadequate and it is more appropriate to start with
either rosuvastatin 10 mg or 20 mg.
<
The information from this evaluation program will provide Indian clinicians a basis for
optimizing their rosuvastatin regimen in the management of dyslipidemia to achieve
guideline recommended lipid goals and reduce cardiovascular risk
Rosuvastatin 20 mg
<
70
61.29
<
0
Significant Reduction in TGs with Rosuvastatin
10 mg and 20 Vs 5 mg
71.79
70
Rosuvastatin 10 mg or 20 mg as the initial starting doses would better achieve the
guideline recommended LDL-C goals in CHD/CHD equivalent population
Reduction at
week 8
Rosuvastatin 10 mg
83.33
79.2
<
Baseline
Rosuvastatin 5 mg
12.5
20
20 mg
The additional decreases observed in LDL-C cholesterol with each doubling of doses of
rosuvastatin in this study in Indian population is in line with similar associations seen in
Western and other Asian populations
-38.22%
127.3
50
30
10 mg
<
166.9
100
40
85.93
5 mg
All three doses resulted in significant reductions in LDL-C from baseline over 8 weeks &
dose responses were consistent as in other studies 6-10
214.2
200
50
80
87.09
91.66
<
0
-10
50
90
94.44
Conclusion
Results - Primary Endpoints
300
51.61
60
More than three-fourth (75.35%) on rosuvastatin attained
NCEP ATP III defined LDL-C targets for their risk category
< Registered in Clinical Trials Registry India CTRI/2011/11/002133
20mg
66.66
70
Overall population
< Secondary outcome measure: Proportion of patients achieving NCEP ATP III defined
10mg
77.7
74.19 74.19
94.73
20 mg
0
< Primary outcome measure: % change from baseline in LDL-C, total cholesterol, HDL-C
5mg
10 mg
10
< Compliance was monitored by a dosing sheet provided to patients
-5
5 mg
83.33
78.12
100
100
88.8
Risk groups
No statin/hypolipidemic therapy in preceding 3 months at entry into the study
Daily dose
80
92.59
% of patients attaining nonLDL-C target
< Multi-centric, open-label, parallel group study across 14 sites with 219 Indian hyperlipidemia
90
92.1
Non-HDL-C Goals
References
1. Circulation 1998;97:1837-47. 2. JAMA 1986;256:2823-8. 3. JAMA 1984;251:351-64. 4. Cardiology. 2003;99(3):126-39. 5. Future Lipidology.
2007;2(2):127-141. 6. Am J Cardiol. 2003;91(1):33-41. 7. Am J Cardiol. 2001;88(5):504-508. 8. J Cardiovasc Risk. 2001;8(6):383-390. 9. Am J Cardiol.
2010;105(1):69-76. 10. J Atheroscler Thromb. 2003;10(6):329-336.