This document discusses the benefits of high-dose statin therapy for patients with acute coronary syndrome (ACS). It summarizes several studies that found high-dose statin therapy started very early (within 24 hours) for ACS patients was associated with reduced mortality. One study of over 10,000 ACS patients found very early statin therapy reduced 7-day and 30-day mortality. Another study found high-dose atorvastatin improved coronary flow and ST segment resolution in STEMI patients compared to low-dose atorvastatin. The document also notes that statin therapy duration is important, with one study finding risk of further cardiovascular events was lower the longer patients continued high-dose atorvastatin therapy.

1. Dr. Rajeev Agarwala
Jaswant Rai Speciality Hospital, Meerut.
E-mail : rajeev_jrsh@yahoo.co.in
High Dose Statin: The Evidence,
Choice and Duration of Therapy

2. Collateral Therapeutics
Lipid abnormalities Inflammation
Coagulation cascade
Thrombus

3. 4. Plaque rupture,4. Plaque rupture,
cholesterol content,cholesterol content,
inflammation (hs-CRP)inflammation (hs-CRP)
(statins)(statins)
3. Platelet adhesion/3. Platelet adhesion/
activation/aggregationactivation/aggregation
(aspirin, clopidogrel,(aspirin, clopidogrel,
GP IIb/IIIa inhibitors)GP IIb/IIIa inhibitors)
2. Activation of clotting2. Activation of clotting
cascade – thrombincascade – thrombin
(heparin/LMWH)(heparin/LMWH)
1. Downstream from thrombus1. Downstream from thrombus
myocardial ischaemia/necrosismyocardial ischaemia/necrosis
((ββ-blockers, nitrates etc)-blockers, nitrates etc)
PlateletPlatelet
GP IIb/IIIaGP IIb/IIIa
receptorreceptor
FibrinogenFibrinogen
ThrombinThrombin
FibrinFibrin
clotclot
Pathophysiology of ACS and potentialPathophysiology of ACS and potential
pharmacological interventionspharmacological interventions

4. GUSTO IIb/PRISM: Early reduction in death/MIGUSTO IIb/PRISM: Early reduction in death/MI
in patients on lipid-lowering therapyin patients on lipid-lowering therapy
• GUSTO IIbGUSTO IIb
– Retrospective analysis of 12,630 ACS patients (Retrospective analysis of 12,630 ACS patients (±±STST
elevation)elevation)
– 52% reduction in 6-month mortality (RR 0.48, 95%52% reduction in 6-month mortality (RR 0.48, 95%
CI 0.28-0.83)CI 0.28-0.83)
• PRISMPRISM
– Retrospective analysis of 1616 patientsRetrospective analysis of 1616 patients
– Death/MI rate at 30 days was significantly lower inDeath/MI rate at 30 days was significantly lower in
these patients (these patients (pp<0.01)<0.01)
Aronow et al, Hamm et al (AHA 2000)Aronow et al, Hamm et al (AHA 2000)

5. Early Striking Mortality Reduction
After ACS by Lipid-lowering Therapy
GUSTO IIbGUSTO IIb && PURSUIT, 1993-98PURSUIT, 1993-98
(20,809 patients)(20,809 patients)
RIKS-HIA 1995-98RIKS-HIA 1995-98
(19,599 patients)(19,599 patients)
Stenestrand et al, JAMA 2001;285:430Stenestrand et al, JAMA 2001;285:430 Aronow et al, Lancet 2001;357Aronow et al, Lancet 2001;357::10631063
Relative risk 0.75Relative risk 0.75
95% CI 0.63-0.8995% CI 0.63-0.89
Log-rank p<0.0001Log-rank p<0.0001
RR 0.75RR 0.75
95% CI 0.63-0.8995% CI 0.63-0.89 p=p=0.0010.001
Statin
(n=5528)
No statin
(n=14071)
p<0.0001
RR 0.48RR 0.48
95% CI 0.37­0.6395% CI 0.37­0.63
No LL
(n=17156)
Lipid-lowering
(n=3653)

6. THE EVIDENCE

7. Very early (<24 hrs) statin therapy in patients with ACS
associated with reduced mortality
Lenderink et al, Eur Heart J
2006;27:1799-1804
HR 0.44HR 0.44 (95% CI 0.31-(95% CI 0.31-
0.64)0.64)
77
HR 0.16HR 0.16 (95% CI 0.08-0.37)(95% CI 0.08-0.37)
(n=1426)(n=1426)
(n=6771)(n=6771)
Euro Heart Survey 2000-01 (10,484 patiens)Euro Heart Survey 2000-01 (10,484 patiens)

8. Early statins and mortality in Euro Heart Survey
Lenderink et al, Eur Heart J 2006;27:1799-1804
7-day7-day
YESYES
(n=1426)(n=1426)
NONO
(n=6771)(n=6771)
Unadjusted HRUnadjusted HR
(95%CI)(95%CI)
Adjusted HRAdjusted HR
(95%CI)(95%CI)
STEMISTEMI 0.3%0.3% 3.4%3.4% 0.090.09 (0.02–0.35)(0.02–0.35) 0.170.17 (0.04–0.70)(0.04–0.70)
NonSTENonSTE
MIMI
0.6%0.6% 1.5%1.5% 0.410.41 (0.15–1.1)(0.15–1.1) 1.01.0 (0.34–2.9)(0.34–2.9)
AllAll 0.4%0.4% 2.6%2.6% 0.160.16 (0.08–0.37)(0.08–0.37) 0.340.34 (0.15–0.79)(0.15–0.79)
30-day30-day
STEMISTEMI 1.6%1.6% 5.9%5.9% 0.250.25 (0.13–0.47)(0.13–0.47) 0.490.49 (0.25–0.95)(0.25–0.95)
NonSTENonSTE
MIMI
2.7%2.7% 3.5%3.5% 0.780.78 (0.47–1.3)(0.47–1.3) 1.61.6 (0.95–2.8)(0.95–2.8)
AllAll 2.3%2.3% 5.0%5.0% 0.440.44 (0.31–0.64)(0.31–0.64) 0.900.90 (0.60–1.3)(0.60–1.3)

9. STATIN STEMI Study
A total 171 patients with STEMI were randomized to 80-mg
atorvastatin (n=86) or 10-mg atorvastatin (n=85) arms for
pre-treatment before PCI.
After PCI, both groups were treated with atorvastatin (10
mg)
End points were
TIMI frame count,
myocardial blush grade, and
ST-segment resolution at 90 min after PCI
J Am Coll Cardiol Intv 2010;3:332–9

10. STATIN STEMI: Study Design

11. TIMI frame count (in Seconds)
Atorvastatin 80 mg Atorvastatin 10 mg
0
5
10
15
20
25
30
35
26.9
31.4
P=0.01
Coronary Perfusion was better and faster in
atorvastatin 80 mg group than in atorvastatin
10 mg group J Am Coll Cardiol Intv 2010;3:332–9

12. Mean ST segment resolution
Atorvastatin 80 mg Atorvastatin 10 mg
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
61.8
50.6
Average ST segment resolution was better in
atorvastatin 80 mg Vs 10 mg group
J Am Coll Cardiol Intv 2010;3:332–9

13. Complete ST segment resolution
Atorvastatin 80 mg Atorvastatin 10 mg
0
5
10
15
20
25
30
35
40
45
39.5
23.8
p=0.03
More patients achieved complete ST segment
resolution in atorvastatin 80 mg Vs 10 mg group
J Am Coll Cardiol Intv 2010;3:332–9

14. STATIN- STEMI: ST resolution and
MACE
Atorvastatin 80 mg is associated with:
•Significantly better ST resolution
•Trend for lower MACE

15. STATIN STEMI: Conclusion
High-dose atorvastatin pre-treatment before
PCI improved immediate coronary flow
after primary PCI compared with low-dose
atorvastatin .
J Am Coll Cardiol Intv 2010;3:332–9

16. Statin therapy significantly reduced the risk of the composite
primary endpoint J Am Coll Cardiol 2011;58:1664–71

17. Hulten et al, Arch Intern Med 2006

18. Early statin treatment reduces 1-year mortality in
AMI survivors
Stenestrand U, Wallentin L. JAMA
2001;285:430–436
RR 0.75 (95% CI 0.63-0.89)RR 0.75 (95% CI 0.63-0.89)
p 0.001p 0.001
RIKS-HIA database (19,599 patients)RIKS-HIA database (19,599 patients)

19. Statin Therapy and Outcome during Hospitalization for ACS
On-statin treatment and ACS presentation in GRACE
Spencer et al, Ann Intern Med 2004;
140: 857 - 866
32
52
30
30
38
18
0%
20%
40%
60%
80%
100%
No Yes
STEMI
NSTEMI
Unstable Angina

20. Effect of statins on arrhythmia related
mortality in STEMI
Non-sustaained ventricular tachycardia (NSVT) is
an independent factor affecting mortality after ACS*
In German ACS registry, data from 3137 patients
with STEMI and in-hospital Holter monitoring were
analysed for association with statin therapy and
NSVT related mortality upto 1 yr
NSVT related Mortality was evaluated in presence
or absence of statin therapy at discharge
* Circulation 1993;87:312–322 Eur Heart J. 2005 Jun;26(11):1078-85.

21. Statin therapy can neutralize effect of non-
sustained ventricular tachycardia (NSVT) on
mortality in STEMI
Not giving statin at time of hospital discharge
in STEMI patients, increase NSVT related
mortality by 3 times.
Eur Heart J. 2005 Jun;26(11):1078-85.

22. VIRHISTAMI Study
Objective: To evaluate effect of low Vs high-dose statin on necrotic
core in coronary plaques as assessed by intravascular ultrasound -
virtual histology
87 STEMI patients were given low Or high dose statin for 12
months duration
The plaque component necrotic core (%) was measured at baseline
and at 12 months
High dose
Low dose
0 2 4 6 8 10 12 14 16
14.2
7.6 Reduction in Necrotic
Core (%)
Only High dose statin was effective for plaque
regression in the STEMI patients
* Vs Baseline EuroIntervention. 2012 Sep 18. pii: 20110313-03
P=0.29P=0.29*
P=0.003*

23. THE DURATION

24. • In a tertiary care hospital in Italy, 1321 ACS patients
who were discharged with 80 mg/day atorvastatin were
followed up for 1 yr.
• Any change in Atorvastatin dose or switch over was
recorded.
• Patients who continued 80 mg/day for 1 yr were
compared to those who reduced atorvastatin dose or
switch over to another statin
• Primary end point: All cause death, non fatal MI or non
fatal stroke
“San Filippo Neri” Study, Italy
International Journal of Cardiology 152 (2011) 56–60

25. Risk of CV event was inversely proportional to
duration of atorvastatin 80 mg/day therapy
International Journal of Cardiology 152 (2011) 56–60
“San Filippo Neri” Study, Italy

26. Conclusion
• For optimum cardiovascular benefits, Atorvastatin 80
mg/day should be continued for at least 1 yr (except
when patient has intolerable ADRs to the drug)
• Reducing dose of atorvastatin or switch over to other
statins increase the risk of adverse CV events
International Journal of Cardiology 152 (2011) 56–60
“San Filippo Neri” Study, Italy

27. And this is not the 1st
evidence
• Switch over to simvastatin from atorvastatin led to
30% increase in CV events in UK over 1.2 yrs*
• Switch over from intensive lipid lowering to
moderate therapy (due to change in national policy)
tripled the CV events within 6 months in New Zea
land and it was reversed by starting intensive
therapy
* Br J Cardiol 2007;14:280–5
** Lancet 1998;352:1830–1

28. Effects of the synergistic actions
between PCI-statins
• Stabilization and regression of atherosclerotic plaque
• Prevention of peri-procedural infarct
• Prevention of restenosis
• Prevention of contrast induced nephropathy
• Improvement of slow flow
Clin Invest Arterioscl. 2012;xxx(xx):xxx---xxx in press

29. PROVE IT-TIMI 22: treatment effects stratified by
PCI for the index ACS event
Wiviott et al, Circulation 2006;113:1426
0-4 months0-4 months Trial durationTrial duration
Statin treatmentStatin treatment
4
4,7
7,1
10,9
10,19,9
2,8
3,9
0
2
4
6
8
10
12
PCI no PCI PCI no PCI
Moderat e (prava 40 mg)
I ntensive (at orva 80 mg)
p 0.07p 0.07
p 0.01p 0.01
NSNS
NSNS

30. Statin therapy at discharge was associated with a significant reduction
in 1-year mortality after primary angioplasty for STEMI.
Therefore, the use of statins is highly recommended in these patients

31. Statin therapy pre-PCI is an independent
predictor of survival
Chan et al, Circulation 2002;105:691
6-month mortality of patients pretreated with statins (n= 1337) vs those
not statins pretreated (n=3715) at the time of PCI

32. Preprocedural Statin Reduces the Extent of Periprocedural Non-Q-
Wave Myocardial Infarction
Herrmann et al, Circulation.
2002;106:2180
0
2
4
6
8
10
control on statincontrol on statin
6.0%
0.4%
CK > 3XUNL
p<0.01p<0.01
n=56
P=0.18, log-rank
n=211

33. Statin therapy, inflammation and recurrent
coronary events following PCI
Walter et al, J Am Coll Cardiol
2001;37:839

34. Pre-PCI statin Rx reduces the incidence of
large peri-procedural nonQ-AMI
Briguori et al,Briguori et al, Eur Heart JEur Heart J 20042004;; 2525:: 1822–18281822–1828
Pasceri et al, Circulation 2004;110:674Pasceri et al, Circulation 2004;110:674
8,0
5,0
15,6
18,0
0,0
5,0
10,0
15,0
20,0
25,0
Briguoli (n.451) Pasceri (n.153)
St at in No st at in
OR 0.19OR 0.19 (95% CI 0.05-0.57)(95% CI 0.05-0.57)
p = 0.02
OR 0.47OR 0.47 (95% CI 0.26–0.86)(95% CI 0.26–0.86)
p = 0.01
PeriproceduralAMI(%)

35. 7-day atorvastatin pretreatment decreases adhesion
molecules after PCI
Patti et al, J Am Coll Cardiol
2006;48:1560
atorvastatinatorvastatin
placeboplacebo

36. Patti et al, J Am Coll Cardiol
2007;49:1272
5%5%
p 0.01p 0.01
17%17%
5%5%
p 0.01p 0.01
17%17%

37. Atorvastatin Pretreatment Improves Outcomes in
Patients With ACS Undergoing Early PCI
ARMYDA-ACS Randomized Trial
Patti et al, J Am Coll Cardiol
2007;49:1272

38. Atorvastatin Pretreatment Improves Outcomes in
Patients With ACS Undergoing Early PCI
Results of the ARMYDA-ACS Randomized Trial
Patti et al, J Am Coll Cardiol
2007;49:1272

39. Atorvastatin and CIN (contrast-induced nephropathy)
in PCI for STEMI patients
161 STEMI patients undergoing emergency PCI
were randomized to atorvastatin 80 mg or
placebo before PCI
All patients received atorvastatin 40 mg/day
after PCI
The primary end point was incidence of CIN.
Cardiology. 2012;122(3):195-202

40. Atorvastatin 80 mg placebo
0
2
4
6
8
10
12
14
16
18
2.6
15.7
CIN (%)
P=0.01
Atorvastatin and CIN (contrast-induced nephropathy)
in PCI for STEMI patients
RESULTS: % patients developing CIN
Cardiology. 2012;122(3):195-202
High dose atorvastatin pre-treatment before PCI in
STEMI patients significantly reduces CIN

41. THE MECHANISM

42. How can High dose statin
produces immediate benefits in
STEMI?

43. Pleiotropic benefits
• Anti-inflammatory
• Anti-oxidant
• Improves endothelial function (NO).
• Plaque stabilization
• Anti-platelet
• Fibrinolytic
• Anti-proliferative ….Many more
•Pleiotropic benefits are dose dependent
•Pleiotropic benefits appears much before the lipid
lowering effects

44. Potential mechanisms by which statins act
rapidly and favorably in ACS
Improve endothelial integrity & vasomotion
Decrease plaque matrix degradation
Reduce plaque inflammation
Reduce platelet aggregability and thrombus
formation
Decrease reperfusion injury

45. • An immediate significant effect of just a single dose of
statin has been previously reported
Immediate functions of statins
Ostadal et al. demonstrated that a single dose of
cerivastatin at the time of admission of patients with
unstable angina or non-ST elevation MI positively
influences the inflammatory parameters CRP and
interleukin-6 at 24 hours
(Mol Cell Biochem 2003;246:45-50)
Romano et al. described that a 24-h treatment with
lovastatin and simvastatin induces inhibition of
monocyte chemotactic protein-1 (MCP-1) synthesis in
mononuclear and endothelial cells in vitro
(Lab Invest 2000;80:1095-1100)
Statins indeed have beneficial effects on endothelial
function by a rapid increase in nitric oxide
bioavailability; this effect has been observed as early
as 3 hours following statin administration
(Laufs et al. Circulation 1998;97:1129-1135)

46. Possible mechanisms of the clinical benefit:
Vasodilation of coronary microvessels
N=32 pts without CAD
randomized to placebo
or
atorvastatin (single dose of 40 mg)
transthoracic doppler
evaluation of LAD (baseline and 1
hr)
0
1
2
3
4
Placebo Atorvastatin
Before
After
Coronary flow velocity reserve
(hyperemic/basal peak diastolic velocity)
P<0.01
Am J Cardiol 2005;96:89 –91

47. • Isolated perfused mouse hearts.
• Atorvastatin infused at the initiation of reperfusion.
• Results:
– Within 5 minutes, Atorvastatin activates
• PI3K/Akt signalling pathway.
• eNOS phosphorylation
• Dose dependent reduction of infarct size.

48. Immediate Antiplatelet and
Antioxidant effect of Atorvastatin
• Patients with hypercholesterolemia were randomly allocated to a:
– Mediterranean diet with low cholesterol intake (<300 mg/d; n=15) or
– Atorvastatin (40 mg/d; n=15).
• Oxidative stress assessed by serum Nox2 and urinary isoprostanes.
• Platelet activation assessed by platelet recruitment, platelet isoprostanes,
and thromboxane A(2), platelet Nox2, Rac1, p47(phox), protein kinase C,
vasodilator-stimulated phosphoprotein, nitric oxide, and phospholipase
A(2).
• Oxidative stress and platelet activation were etermined at baseline and
after 2, 24, and 72 hours and 7 days of follow-up.
Circulation. 2012 Jul 3;126(1):92-103
NOX2: NADPH oxidase

49. • Results:
• The atorvastatin-assigned group showed a significant and
progressive reduction of urinary isoprostanes and serum
Nox2, along with inhibition of platelet recruitment, platelet
isoprostanes, Nox2, Rac1, p47(phox), and protein kinase C,
starting 2 hours after administration.
• Platelet phospholipase A(2) and thromboxane A(2)
significantly decreased
• Vasodilator-stimulated phosphoprotein and nitric oxide
increased after 24 hours.
• No changes were observed in the Mediterranean diet group.
Circulation. 2012 Jul 3;126(1):92-103
First evidence suggesting that
atorvastatin acutely and simultaneously
decreases oxidative stress and platelet
activation by directly inhibiting platelet
Nox2 and ultimately platelet
isoprostanes and thromboxane A(2).

50. Early Antiplatelet effect of statin in STEMI
Effect of statins on platelets were measured in 120 STEMI
patients (80 received statin, 40 did not receive)
Platelets were incubated with a statin or placebo for 72 hrs
Effect of statins on platelet function under flow conditions
and platelet aggregation was studied in vitro by
aggregometry.
Platelet incubation with statin compared with placebo
resulted in a lower aggregate-size (29 ± 9 μm(2) vs. 39
± 15 μm(2), p<0.01), and lower surface coverage (8.5 ±
4% vs. 12 ± 4%, p<0.01)
statin therapy produces antiplatelet effects
within 72 hrs in the STEMI patients
Platelets. 2011;22(2):103-10.

51. STATINSSTATINS
↓LDL-C reduction
↑HDL-C Reduction in
chylomicron and
VLDL remnants,
IDL, LDL-C
Reduce plasma ViscosityReduce plasma Viscosity
Altering platelet aggregationAltering platelet aggregation
Suppressing ThrombinSuppressing Thrombin
Suppress inflammation (↓Suppress inflammation (↓
CRP/IL6) Inhibit M.M.P.CRP/IL6) Inhibit M.M.P.
Improve Endothelial functionImprove Endothelial function
Up regulate VasodilatorsUp regulate Vasodilators
(NO/Prostacyclin)(NO/Prostacyclin)Lumen
Lipid
core
Macrophages
Smooth
muscle
cells
Potential mechanisms of benefit of
statins in ACS
Dissociation Vs Association between lipidDissociation Vs Association between lipid
lowering and anti-inflammatory effectslowering and anti-inflammatory effects

52. HIGH DOSE THE SIDE EFFECTS

53. Severe adverse event rates for intensive
vs moderate statin therapy (n. 32,279 pts)
mod. from Cannon et al, J Am Coll Cardiol 2006;48:438
StandarStandar
d dosed dose
HighHigh
dosedose
StandardStandard
dosedose
HighHigh
dosedose
StandardStandard
dosedose
HighHigh
dosedose
PROVE ITPROVE IT
(n=4162)(n=4162)
0%0% 0%0% 0.1%0.1% 0.1%0.1% 1.1%1.1% 3.3%3.3%
AA toto ZZ (n=4497)(n=4497) 0%0% 0.1%0.1% 0.04%0.04% 0.4%0.4% 0.3%0.3% 0.8%0.8%
TNTTNT (n=10001)(n=10001) 0.06%0.06% 0.04%0.04% 0%0% 0%0% 0.2%0.2% 1.2%1.2%
IDEALIDEAL (n=8888)(n=8888) 0.07%0.07% 0.05%0.05% 0%0% 0%0% 0.1%0.1% 1.3%1.3%
SPARCLSPARCL (n=4731)(n=4731) 0.1%0.1% 0.1%0.1% 0.1%0.1% 0.1%0.1% 0.4%0.4% 2.2%2.2%
RhabdomyolysisRhabdomyolysis CPK >10 xULNCPK >10 xULN AST/ALT >3 xULNAST/ALT >3 xULN

55. LIVER EXPERT PANEL: KEY MESSAGES
• There is no proof that statins cause life-threatening liver damage.
• Mild asymptomatic elevations in liver enzymes are found in about 3
patients per 1,000 person-years who participate in clinical trials.
Elevations are reversible on stopping the statin and do not cause lasting
harm.
• Liver failure has been reported in 1 person out of 1 million person-years of
statin use, as well as in 1 person in 1 million people not taking a statin.
• Routine liver function monitoring during statin therapy is not needed. The
Task Force recommends that statin manufacturers work with the FDA to
remove the requirement for liver function monitoring from prescribing
information.

56. Rate of Elevated Liver Enzymes by Statin DoseRate of Elevated Liver Enzymes by Statin Dose
CategoryCategory
JACCJACCJ Am Coll Cardiol 2007;50:409–18
Drug- and dose-specific effects are more important determinants of liver
toxicity than magnitude of LDL-C lowering

57. MUSCLE EXPERT PANEL: KEY MESSAGES
• Though all marketed statins have a small potential for inducing muscle side
effects, 5 in 100,000 patients taking a statin have muscle complaints and are found
to have an increase in muscle enzymes, suggesting muscle injury. This finding is
not statistically significant.
• 1.5-3.0 percent of patients taking a statin complain of muscle pain, weakness, or
cramps. The numbers are similar for patients receiving placebo.
• Exercise, trauma, falls, accidents, seizures, infections, chills, and alcohol and drug
abuse can cause muscle injury. Physicians should carefully identify and address the
risk factors for muscle problems before prescribing a statin.
• Rhabdomyolysis, the most serious potential problem associated with statin
therapy, occurs in about 2 of 100,000 patients taking a statin. This is rarely life
threatening and is reversible when the statin is stopped.

58. Interindividual variability in statin exposure in patients is associated with
uptake and efflux transporter polymorphisms. An algorithm incorporating
genomic and clinical variables to avoid high atorvastatin and rosuvastatin
levels is described
Rosuvastatin and atorvastatin
dosing decision support
algorithm
Circ Cardiovasc Genet. 2013;6:400-408

59. Study Trial Population Regimens Durati
on
(yrs)
New DM Cases in
Compared Regimens
Relative LDL
Reduction
4S Previous MI or angina Simvastatin 40 mg 5.4* 198 (9.4%) 36.7% at 12 mos
HPS History of CVD Simvastatin 40 mg 5.0 335 (4.6%) 29.4% average
in trial
ALLHAT
-LLT
CAD or CAD risk
factors
Pravastatin 40 mg 4.8 238 (7.9%) 18.1% at 24 mos
PROVE-IT-
TIMI-22
Recent ACS Atorvastatin 80 mg vs
pravastatin 40 mg
2.0 101 (5.9%) vs 99 (5.9%) 22%
TNT Stable CAD Atorvastatin 80 mg 5.0 418 (11.0%) 22%
IDEAL Previous MI Atorvastatin 80 mg vs
simvastatin 20 OR 40 mg
4.8* 240 (6.4%) vs 209 (5.6%) 16%
SPARCL Previous stroke or TIA Atorvastatin 80 mg 4.9 166 (8.7%) NA
Jupitor healthy persons without
hyperlipidemia, elevated
high-sensitivity C-reactive
protein levels,
Rosuvastatin 20 mg 1.9
years
3.0% 50%
Meta-Analysis of Impact of Different Types and High
Doses of Statins on New-Onset Diabetes Mellitus
Am J Cardiol 2013;111:1123e1130

60. THE COMPLIACE

61. % STEMI patients receiving statin at discharge in
India and developed countries
Kerala ACS registry NCDR action registry
0
10
20
30
40
50
60
70
80
90
100
69
94.5
%STEMIpatientsreceivingstatinatdischarge
Circulation. 2011; 124: A9151

62. Statin dosage used in pre-PCI and post-PCI period in patients with
UA/NSTEMI and STEMI
Clin. Cardiol. 35, 11, 700–706 (2012)
High-dose statin treatment is being underused despite extensive evidence for patients with
ACS undergoing PCI

63. Difference in High dose statin use in STEMI and
UA/NSTEMI in KOREA
STEMI NSTEMI/UA
0
5
10
15
20
25
19.6
13.7
%patientsreceivingstatinatdischarge
Clin Cardiol. 2012 Nov;35(11):700-6
STEMI NSTEMI/UA
0
5
10
15
20
25
20.1
12.2
%patientsreceivingstatinatdischarge
Use of high dose statin before/after PCI was
more common in STEMI than in UA/NSTEMI,
but still only 1 out of 5 STEMI patients
received such therapy in korea
P < 0.001;
P < 0.001;
Pre-PCIPre-PCI 30 days post-PCI

64. Lipid Management
High-intensity statin therapy should be initiated or continued in all
patients with STEMI and no contraindications to its use.
It is reasonable to obtain a fasting lipid profile in patients with
STEMI, preferably within 24 hours of presentation.
I IIa IIb III
I IIa IIb III
2013 ACCF/AHA Guideline for the
Management of ST-Elevation Myocardial
Infarction
Class I
Level of Evidence B

65. ESC 2012 STEMI GUIDELINES

66. High-dose statins in ACS:
an intriguing hypothesis
• Early benefits derived largely from
the anti-inflammatory effects of
the drug.
• The delayed benefits are lipid-
modulated.
Nissen S, JAMA 2004;292;1365

67. Conclusions
• Benefit of intensive statin therapy is
evident in ACS patients who
underwent PCI
• Pleiotropic effectsPleiotropic effects llikelyikely
• Significantly better myocardial
perfusion with 80 mg atorvastatin
• PProven efficacy in the longroven efficacy in the long--termterm
 aabsence of harmbsence of harm
? Fixed doses / dose titration to achieveFixed doses / dose titration to achieve
specific goalsspecific goals (lipid / anti-inflammatory)(lipid / anti-inflammatory)