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

Why We’ll Never Stop Talking about Dsylipidemia ?

Circulation 1993;88:2548-2555

Coronary Artery Disease (CAD):

Circulation 1993;88:2548-2555

Coronary Angiography

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

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

Cum

ulat

ive

mor

talit

y (%

)

8.0

Men (n=1198) Women (n=546)

Pra PCI Post PCI

8

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

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

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

14

GRACE: Statin Therapy Improved Clinical Outcomes in ACS

0

2

4

6

8

10

12

14

16

18

In-h

ospi

tal e

vent

s (%

)

MI after 24hours

Pulmonaryedema

Cardiogenicshock

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 hospitalNo 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

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

Clin

ical

eve

nts

(%)

* *

*

*

*

* *

* * * *

* *

Statin initiation within 24 hours of hospitalization resulted in a 77% reduction in death compared with no statin use

Very High Risk Subjects

*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)

Mea

n Pe

rcen

t Cha

nge

From

Bas

elin

e in

LD

L-C (±S

E)

-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

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

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

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

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

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

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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

Thank You

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