Pragmatic Use of Rosuvastatin for CVD Prevention

1. “
”
Pragmatic Use of Rosuvastatin
for CVD prevention
Dr Awadhesh Kumar Sharma , DM, FACC, FSCAI, FISC,FICCM
Associate Professor
LPS Institute of Cardiology , Kanpur (UP)

4. “Good” Cholesterol
High levels of HDL have been found to lower
risk of heart attack (American Heart
Association, 2009)
Risk of heart disease increases when there
are lower levels of HDL.
Mostly protein, and few cholesterol
“Help remove cholesterol from artery
walls and transport it to the liver for
elimination from the body”(Simon, 2008
para. 1)
High Density Lipoprotein

5.  LDL: Bad cholesterol that can build up in
the arteries.
 High levels of LDL can increase risk of
heart disease.
 Composed mainly of cholesterol and a
few proteins.
 “Primarily responsible for depositing
cholesterol within arteries” (Simon, 2008
para. 2)
Low Density Lipoprotein

6. http://www.clarian.org/ADAM/doc/OrthopedicsCenter/10/000362.htm

7. Lipid
Transport:
LDL-c : BAD
Cholesterol
HDL-c: GOOD
Cholesterol

8. % of particle
mass in each
Lipoprotein
LDL=High-density lipoprotein;HDL=High-density lipoprotein; VLDL=very low-density lipoprotein.
Circulation. 2002;106(25):3143-342;
RaderDJ,HobbsHH, "Chapter 356.Disordersof Lipoprotein Metabolism“ (Chapter).
Fauci AS,et al:Harrison's Principles of Internal Medicine, 18e: http://www.accessmedicine.com/content.aspx?aID=9143689;
HavelRJ, et al. The Metabolic & Molecular Bases of Inherited Disease. Vol 2. 8th ed. 2001:2705-2716.

9. Yusuf S et al. Lancet. 2004;364:937-52.
N = 15,152 patients and 14,820 controls in 52 countries
PAR = population attributable risk, adjusted for all risk
factors
36
12
7 10
20
33
0
20
40
60
80
100
Smoking Fruits/
veg
Exercise Alcohol Psycho-
social
Lipids All 9 risk
factors
PAR
(%)
14
18
90
Diabetes Abdominal
obesity
Hyper-
tension
50
INTERHEART STUDY
DYSLIPIDEMIA STANDS AT TOP POSITION..

10. AHA 2018 guideline:
Objectives of dyslipidemia management
Primary prevention of CVD
 Without established ASCVD
 Patient is at risk of ASCVD due to
presence of multiple risk factors
Secondary prevention of CVD
 With established ASCVD…

11. AHA 2018
guideline:
Major risk factor can
have impact on Primary
Prevention of CV
Disease
Determinants
for Primary
Prevention of
CVD
Physical
Activity
Healthy Diet
Dyslipidemia
DM
Tobacco Use
CV risk factors
(Obesity, High
blood
HF etc…)

12. ESC 2019 – Target LDL goal for CVD prevention
Mach F et al. European Heart Journal, Volume 41, Issue 1, 1 January 2020, Pages 111–188

13. ESC 2019: Intensity of lipid lowering treatment
Mach F et al. European Heart Journal, Volume 41, Issue 1, 1 January 2020, Pages 111–188

14. Statins can reduce LDL significantly and that’s why statins are
always considered as first line agents for Primary and Secondary
prevention of CVD

15. LDL-c : Lower is better
Stein EA et al. Practice & Research Clinical Endocrinology & Metabolism (2013), http://dx.doi.org/10.1016/ j.beem.2013.10.010

16. ESC 2019 - Absolute reductions in major
vascular events with statin therapy
Mach F et al. European Heart Journal, Volume 41, Issue 1, 1 January 2020, Pages 111–188

17. Low LDL level
is associated
with Low CV
events;
irrespective of
age
Law M R et al. BMJ 2003;326:1423–9.

18. Each 1 mmol/L reduction of LDL gives more CV events reduction according to No. of years in trials and co-
morbid conditions as well
Stein EA et al. Practice & Research Clinical Endocrinology & Metabolism (2013), http://dx.doi.org/10.1016/ j.beem.2013.10.010

19. Role of Rosuvastatin for CVD prevention

20. Rosuvastatin : Reduction in (LDL-C) according to different dose
Olsson AG Cardiovascular Drug ReviewsVol. 20, No. 4, pp. 303–328
-63%

21. STELLAR Study : LDL-C: % Change From Baseline Rosuvastatin 10 to 40 mg vs
Comparators (Wk 6)
P < .001 vs comparators on a mg-to-mg basis. Data presented as means. http://www.fda.gov/OHRMS/DOCKETS/ac/03/slides/3968S1_01_B-AstraZeneca-Efficacy.ppt#14

22. ANDROMEDA & URANUS Studies: LDL-C goal attainment (<100 mg/dL)
in patients with type 2 diabetes and dyslipidemia
Betteridge DJ et al. Diabet Med. 2007;24(5):541-549. Berne C et al. Cardiovasc Diabetol. 2005;4:7

23. Rosuvastatin 20-40 mg has shown > 50% reduction in LDL-C
Circulation. 2019 Jun 18;139(25):e1046-e108

24. ASTEROID: Study design
Nissen SE et al. JAMA. 2006;295:1556-65.
Angiographic CAD (>20% luminal narrowing*)
Statin-naive
N = 507
Rosuvastatin 40 mg qd for 24 months
Primary efficacy parameters:
• Change in % atheroma volume of target vessel
• Change in total atheroma volume in most diseased 10-mm segment
Multicenter, open-label,
blinded end point
IVUS assessment at baseline
and study end
Completed trial
N = 349

25. ASTEROID: Treatment effect on primary efficacy parameters
Nissen SE et al. JAMA. 2006;295:1556-65.
Rosuvastatin can cause significant plaque regression in coronary arteries in
patients of CAD

26. Rosuvastatin 20 mg (N=8901)
MI
Stroke
Unstable
Angina
CVD Death
CABG/PCI
Ridker et al, Circulation 2003;108:2292-2297.
No Prior CVD or DM
Men >50, Women >60
LDL <130 mg/dL
hsCRP >2 mg/L
JUPITER Trial
Use of rosuvastatin for primary prevention of CVD in
patients with apparently normal lipid levels and high hsCRP levels
Placebo (N=8901)
2 yrs follow up

27. Ridker et al, Circulation 2003;108:2292-2297.
JUPITER: Effects of rosuvastatin 20 mg on LDL, HDL, TG, and hsCRP

28. JUPITER: Primary results of MACE reduction
Ridker et al, Circulation 2003;108:2292-2297.

29. HOPE-3: Primary Prevention with Rosuvastatin
 12,705 patients (without CVD + intermediate CV risk) randomised to rosuvastatin 10 mg/day or placebo.
 1st coprimary outcome : Composite of CVD death, nonfatal myocardial infarction, or nonfatal stroke
 2nd coprimary outcome: 1st coprimary outcome + revascularization, heart failure, and resuscitated cardiac arrest.
 CV Risk Feature: 87% Obese/overweight, 38% HT, 18% T2DM/IGT, 27%
Smokers
 The median follow-up : 5.6 years
Yusuf S et al. N Engl J Med 2016; 375:1190-1194

30. HOPE-3 Lipid Lowering CV Outcomes
Outcome
Rosuvastatin
N (%)
Placebo
N (%)
HR
(95% CI)
RRR % p
Co-Primary 1 235 (3.7) 304 (4.8) 0.76 (0.64-0.91) 24 0.002
Co-Primary 2 277 (4.4) 363 (5.7) 0.75 (0.64-0.88) 25 0.0004
CV Death 154 (2.4) 171 (2.7) 0.89 (0.72-1.11) 21 0.31
MI 45 (0.7) 69 (1.1) 0.65 (0.44-0.94) 35 0.02
Stroke 70 (1.1) 99 (1.6) 0.70 (0.52-0.95) 30 0.02
22
Yusuf S et al.N Engl J Med 2016; 375:1190-1194

31. METEOR Trial
Aim: To assess whether statin therapy could slow progression and/or cause
regression of carotid intima-media thickness (CIMT)
Methods: 984 patients with moderately elevated cholesterol and low
risk of CVD
Duration of study – 12 months follow up
Primary efficacy parameters:
• Changes in maximum CIMT of the common carotid artery
Results:
• 49% reduction in LDL-Cholesterol
• The change in maximum CIMT for the 12 carotid sites was -0.0014
Conclusion: Rosuvastatin resulted in statistically significant reductions
in the rate of progression of maximum CIMT
CMIT: Carotid Intima Media Thickness
METEOR: Measuring Effects on Intima-Media Thickness: an Evaluation of
Rosuvastatin
Crouse JR et al. JAMA. 2007 Mar 28;297(12):1344-
53

32. LUNAR study
Aim: Comparison of lipid-modifying efficacy of Rosuvastatin
versus Atorvastatin in patients with ACS
Methods: 825 patients with acute coronary syndrome
Duration of study – 12 weeks follow up
Treatment: Rosuvastatin 40 mg vs. Atorvastatin 80 mg
Results:
• Lowering LDL cholesterol was significantly greater with
Rosuvastatin (46.8%) compared to Atorvastatin (42.7%).
• Increase in HDL cholesterol were significantly greater with
Rosuvastatin (11.9%) compared to Atorvastatin (5.6%)
Conclusion: LUNAR study show that Rosuvastatin 40 mg more
effectively decreased LDL cholesterol, increased HDL cholesterol,
and improved other blood lipid parameters than Atorvastatin 80
mg in patients with acute coronary syndrome.
Pitt B. et al. Am J Cardiol. 2012 May 1;109(9):1239-46

33. ROMA Trial
Aim: To assess the efficacy of the high-dose rosuvastatin pre-administration in
reducing periprocedural myocardial necrosis and MACCE in patients undergoing
elective PCI.
Methods: 160 patients stable angina undergoing elective PCI
Duration of study – 12 months follow up
Primary efficacy parameters:
• Incidence of periprocedural myocardial necrosis.
Secondary end points:
• MACCE (cardiac death, all-MI,stroke and TVR) at 30-day and 12-month follow-up
MACCE: Major Adverse Cardiac and Cerebrovascular Events
ROMA: ROsuvastatin and Atorvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of
MyocArdial periprocedural necrosis
Catheterization and Cardiovascular Interventions 2013; 81:E36–
E43

34. ROMA Trial: Results
Catheterization and Cardiovascular Interventions 2013; 81:E36–
E43

35. ROMA Trial: MACCE Reduction @30 days and 12 months
Results:
• Periprocedural MI incidence - 26.4% Control group (CG) vs. 8.7% Rosuvastatin group (RG)
• MACCE was higher in CG than in the RG.
• For 30 days - 30.0% (CG) vs. 8.7% (RG)
• 12 months 35.0% (CG) vs. 12.5% (RG)
Conclusion: High loading dose of rosuvastatin within 24 hour before elective PCI seems to decrease the
incidence of periprocedural myocardial necrosis during a period of 12-months compared to the standard
treatment.
Catheterization and Cardiovascular Interventions 2013; 81:E36–
E43

36. ROZEL Study : Study Flow Chart
Su Q. et al. Adv Ther (2023) 40:5285–5299
Efficacy and Safety of Single-
Pill Combination of
Rosuvastatin and Ezetimibe in
Patients with Primary
Hypercholesterolemia
Inadequately Controlled by
Statin Treatment

37. ROZEL Study : Study Results
LDL reduction % of patients with target LDL reduction
Su Q. et al. Adv Ther (2023) 40:5285–5299
• Conclusion: R10/E10 improves the LDL-C reduction with a favorable safety profile in
participants with primary hypercholesterolemia not adequately controlled on statin
therapy compared with R10.
• Improving LDL-C target achievement without adequate control of statin therapy might
reduce the burden of CVD.

38. Summary
 CVD and related mortality is growing epidemic, wherein dyslipidemia is always a major risk factor
 All major guidelines recommend, Rosuvastatin as High and moderate intensity statin for significant LDLc
reduction
 Statins are considered as a first line agents for primary and secondary CVD prevention
 Rosuvastatin has more robust clinical trial data for primary prevention of CVD in high risk patients
 Rosuvastatin has shown significant improvement in Atheroma volume, CIMT and MACCE reduction as
well

39. Don’t let it control You
Control your Cholesterol
THANKS