Dr. A. Fauzi Yahya, SpJP (K), FIHA, FAsCC. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com

1. Strategy to go for goal
in Dyslipidemia with ACS patients
A. Fauzi Yahya
Department of Cardiology and Vascular Medicine
Faculty of Medicine
Padjadjaran University/ Hasan Sadikin General Hospital
Bandung-Indonesia

2. Why We’ll Never Stop Talking about Dsylipidemia ?
Circulation 1993;88:2548-2555

3. Coronary Artery Disease (CAD):
Circulation 1993;88:2548-2555

4. Coronary Angiography

5. Braunwald (1996)
Risk of death in patients with coronary heart disease is
greatest early after an ACS
Deaths/100 patients/month
Time (months after hospital admission)
Acute MI
Unstable angina
Stable angina
0
5
10
15
20
25
0 1 2 3 4 5 6

6. 6
Men and Women With ACS Are at High Risk of
Early Mortality
CCU=coronary care unit.
Adapted from Perers E et al. Int J Cardiol. 2005;103:120-127.
30-day mortality in men and women with ACS
10.0
6.0
4.0
2.0
0.0
0 5 10 15 20 25 30
Days after admission to CCU
Cumulativemortality(%)
8.0
Men (n=1198)
Women (n=546)

7. Pra PCI Post PCI

8. 8

9. 4. Plaque rupture,
cholesterol content,
inflammation (hs-CRP)
(statins)
3. Platelet adhesion/
activation/aggregation
(aspirin,clopidogrel,ticagrelor,
prasugrel GP IIb/IIIa inhibitors)
2. Activation of clotting
cascade – thrombin
(heparin/LMWH)
1. Downstream from thrombus
myocardial ischaemia/necrosis
(β-blockers, nitrates etc)
Pathophysiology of ACS and potential
pharmacological interventions
Platelet
GP IIb/IIIa
receptor
Fibrinogen
Thrombin
Fibrin
clot

10. XXII ESC Congress (2000)
Statins Revascularisation Combined therapy
0
10
20
30
40 34%
36%
64%
50
60
Swedish registry: Early statin and revascularisation
significantly reduces mortality
70
Relative risk reduction in
mortality after 1 year

12. Plaque Stabilization/Regression
Unstable plaque
Fibrous cap
Lipid core
Stable plaque
Lipid core
Fibrous cap
Inflammatory
cells
Fewer
inflammatory
cells
Toschi V et al. Circulation. 1997;95:594-599; Libby P. Circulation. 1995;91:2844-2850.

13. 13

14. 14
GRACE: Statin Therapy Improved Clinical Outcomes in ACS
0
2
4
6
8
10
12
14
16
18
In-hospitalevents(%)
MI after 24
hours
Pulmonary
edema
Cardiogenic
shock
Cardiac
arrest
VT/VF Stroke Death Death, stroke,
or in-hospital
MI
Hospital outcomes of patients with ACS according to statin use
On statins and continued Began in hospital
No statin use Prior statin discontinued on admission
Discontinuation of statin therapy was associated with worse clinical outcomes in GRACE
Adapted from Spencer FA et al. Ann Intern Med. 2004;140:857-866.
VT=ventricular tachycardia; VF=ventricular fibrillation.

15. 15
NRMI: Statin Use Within 24 Hours of AMI Is Associated With
Reduced Early Morbidity and Mortality
Adapted from Fonarow GC et al. Am J Cardiol. 2005;96:611-616.
*P<.001 vs No/No patients.
Yes/yes=patients continued on statin therapy; no/yes=patients newly started on statin therapy; no/
no=patients who did not receive statin therapy before or within the first 24 hours of hospitalization; yes/
no=patients in whom statin therapy was discontinued.
Clinical events by statin use
0
5
10
15
20
25
30
Death Heart failure Rupture Shock VT/VF Reinfarct
Yes/Yes No/Yes No/No Yes/No
Clinicalevents(%)
*
*
*
*
*
* *
*
*
**
* *
Statin initiation within 24 hours of hospitalization resulted
in a 77% reduction in death compared with no statin use

16. Very High Risk Subjects

18. *P<.002 vs atorvastatin 20 mg, 40 mg; simvastatin 20 mg, 40 mg, 80 mg; pravastatin 20 mg, 40 mg
** P<.002 vs atorvastatin 40 mg; simvastatin 40 mg, 80 mg; pravastatin 40 mg
1. Jones PH, Davidson MH, Stein EA, et al. Am. J. Cardiology 2003; 93: 152-160.
2. Data on file, DA-CRS-02 AstraZeneca Pharmaceuticals LP, Wilmington, DE.
–52.4
* –55.0
**
–51.1
20 40 20 40 80 20 40 80 20 40
–60
–50
–40
–30
–20
–10
0
Rosuvastatin
(mg)
Pravastatin
(mg)
Atorvastatin
(mg)
Simvastatin
(mg)
MeanPercentChangeFrom
BaselineinLDL-C(±SE)
-35.0
-29.7
-24.4
-47.8
-42.6
–45.8
-38.8
Percentage Change in LDL-C: Pairwise Comparison
of Rosuvastatin 20 mg and 40 mg

19. Lipids
Safety
Lipids
CRP
Safety
Lipids
CRP
Safety
Patients (n=825)
18–75 years
Hospitalised for ACS (STEMI, NSTEMI,
UA) within 48hrs of ischaemic symptoms
LDL-C >70mg/dL (~1.8 mmol/L)
TGs <500 mg/dL (~5.6 mmol/L)
Rosuvastatin 40 mg (n=270)
Atorvastatin 80 mg (n=278)
Rosuvastatin 20 mg (n=277)
Visit:
Week:
1 4
6
5
12
2
0
3
2
Screening / baseline
blood analysis
LUNAR
Study Design
ACS = acute coronary syndrome, STEMI = ST elevation myocardial infarction,
NSTEMI = non-ST elevation myocardial infarction, UA = unstable angina, LDL-C = low-
density lipoprotein cholesterol, TGs = triglycerides, CRP = C-reactive protein
Prospective, multi-centre, randomised, open-label,
parallel-group phase IIIb study
Symptom
Onset
Average time from symptom onset to
study drug treatment = 3.9 days
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015

20. LUNAR
Primary Endpoint
*p <0.05; **p <0.01 versus atorvastatin 80 mg
Time (weeks)
0 2 4 6 8 10 12
Rosuvastatin 20mg
Rosuvastatin 40mg
Atorvastatin 80 mg
0
-10
-20
-30
-40
-50
-60 *
**
*
Mean
Change in
LDL-C from
Baseline (%)
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015

21. 9.7
11.9
5.6
0
5
10
15
**
Mean change
in
HDL-C from
baseline (%)
Rosuvastatin
20 mg
Rosuvastatin
40 mg
Atorvastatin
80 mg
***
LUNAR
Secondary Endpoint
**p< 0.01, *** p<0.001 versus atorvastatin 80 mg
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015

22. LUNAR
Secondary Endpoints
** p<0.01, ***p<0.001 versus atorvastatin 80 mg †p< 0.05, ††
p<0.01 versus rosuvastatin 20mg
-100
-80
-60
-40
-20
0
20
Mean
Change in
Parameter
from
Baseline (%)
Rosuvastatin 20mg
Rosuvastatin 40mg
Atorvastatin 80mg
***
***
***
**
***
***
†
††
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015

23. LUNAR
Safety & Tolerability
Variable
Rosuvastatin
20 mg/day
(n=267)
Rosuvastatin
40 mg/day
(n=263)
Atorvastatin
80 mg/day
(n=269)
Any Serious AE* 28 (10.5%) 23 (8.7%) 38 (14.1%)
Serious Cardiovascular AE* 9 (3.4%) 5 (1.9%) 6 (2.2%)
Unstable angina 4 (1.5%) 3 (1.1%) 3 (1.1%)
Myocardial infarction 5 (1.9%) 2 (0.8%) 2 (0.7%)
Cerebrovascular accident 0 0 1 (0.4%)
Withdrawal due to AE 10 (3.7%) 16 (6.1%) 25 (9.3%)
Musculoskeletal and connective
tissue disorders
5 (1.9%) 6 (2.3%) 17 (6.3%)
Death* 0 2 (0.8%) 1 (0.4%)
AE = adverse event
*None of the serious AEs, serious cardiovascular AEs or deaths were considered by the investigators to be related to study treatment
Pitt B et al. Am J Cardiol 2012; doi:10.1016/j.amjcard.2011.12.015

24. 24
Conclusion
♦ ACS is common and represents a large burden on
clinical, social, and health care systems globally
♦ A significant proportion of the burden is borne in the
immediate post-ACS period (<30 days)
♦ Observational evidence suggests pretreatment with
statins can impact the ACS burden:
♦ Rosuvastatin has beneficial effect in ACS
patient

25. Thank You
25