14.09.13 high dose statin

Dr. Rajeev AgarwalaJaswant Rai Speciality Hospital, Meerut.

E-mail : [email protected]

High Dose Statin: The Evidence,

Choice and Duration of Therapy

Collateral Therapeutics

Lipid abnormalities Inflammation

Coagulation cascade

Thrombus

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 clotting 2. Activation of clotting cascade – thrombincascade – thrombin (heparin/LMWH)(heparin/LMWH)

1. Downstream from thrombus1. Downstream from thrombus myocardial ischaemia/necrosismyocardial ischaemia/necrosis ((-blockers, nitrates etc)-blockers, nitrates etc)

PlateletPlatelet

GP IIb/IIIaGP IIb/IIIareceptor receptor

FibrinogenFibrinogenThrombinThrombin

Fibrin Fibrin clotclot

Pathophysiology of ACS and potential Pathophysiology of ACS and potential pharmacological interventionspharmacological interventions

GUSTO IIb/PRISM: Early reduction in death/MI GUSTO 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 (±±ST ST

elevation)elevation)– 52% reduction in 6-month mortality (RR 0.48, 95% CI 52% reduction in 6-month mortality (RR 0.48, 95% CI

0.28-0.83)0.28-0.83)

• PRISMPRISM – Retrospective analysis of 1616 patientsRetrospective analysis of 1616 patients– Death/MI rate at 30 days was significantly lower in these Death/MI rate at 30 days was significantly lower in these

patients (patients (pp<0.01)<0.01)

Aronow et al, Hamm et al (AHA 2000)Aronow et al, Hamm et al (AHA 2000)

Early Striking Mortality Reduction After ACS by Lipid-lowering Therapy

GUSTO IIb GUSTO IIb && PURSUIT, PURSUIT, 1993-981993-98 (20,809 patients) (20,809 patients)

RIKS-HIA 1995-98RIKS-HIA 1995-98 (19,599 patients)(19,599 patients)

Stenestrand et al, JAMA 2001;285:430 Stenestrand et al, JAMA 2001;285:430 Aronow et al, Lancet 2001;357Aronow et al, Lancet 2001;357::10631063

Relative risk 0.75 Relative risk 0.75 95% CI 0.63-0.8995% CI 0.63-0.89

Log-rank p<0.0001 Log-rank p<0.0001

RR 0.75 RR 0.75 95% CI 0.63-95% CI 0.63-

0.890.89p=p=0.0010.001

Statin (n=5528)

No statin (n=1407

1)

p<0.0001

RR 0.48RR 0.4895% CI 0.37 95% CI 0.37

0.630.63

No LL (n=17156)

Lipid-lowering (n=3653)

THE EVIDENCE

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 0.44 HR 0.44 (95% CI 0.31-(95% CI 0.31-0.64)0.64)

77

HR 0.16 HR 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)

Early statins and mortality in Euro Heart Survey

Lenderink et al, Eur Heart J 2006;27:1799-1804

7-day7-day

YES YES (n=1426(n=1426

))

NO NO (n=6771(n=6771

))

Unadjusted HR Unadjusted HR (95%CI)(95%CI)

Adjusted HR Adjusted HR (95%CI)(95%CI)

STEMISTEMI 0.3%0.3% 3.4%3.4% 0.09 0.09 (0.02–0.35)(0.02–0.35) 0.17 0.17 (0.04–0.70)(0.04–0.70)

NonSTENonSTEMIMI

0.6%0.6% 1.5%1.5% 0.41 0.41 (0.15–1.1)(0.15–1.1) 1.0 1.0 (0.34–2.9)(0.34–2.9)

AllAll 0.4%0.4% 2.6%2.6% 0.16 0.16 (0.08–0.37)(0.08–0.37) 0.34 0.34 (0.15–0.79)(0.15–0.79)

30-day30-day

STEMISTEMI 1.6%1.6% 5.9%5.9% 0.25 0.25 (0.13–0.47)(0.13–0.47) 0.49 0.49 (0.25–0.95)(0.25–0.95)

NonSTENonSTEMIMI

2.7%2.7% 3.5%3.5% 0.78 0.78 (0.47–1.3)(0.47–1.3) 1.6 1.6 (0.95–2.8)(0.95–2.8)

AllAll 2.3%2.3% 5.0%5.0% 0.44 0.44 (0.31–0.64)(0.31–0.64) 0.90 0.90 (0.60–1.3)(0.60–1.3)

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

STATIN STEMI: Study Design

TIMI frame count (in Seconds)

Atorvastatin 80 mg Atorvastatin 10 mg 0

5

10

15

20

25

30

35

26.9

31.4

Series1

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

Mean ST segment resolution


10152025303540455055606570

61.8

50.6

Series1

Average ST segment resolution was better in atorvastatin 80 mg Vs 10 mg group


Complete ST segment resolution


5

10

15

20

25

30

35

40

45

39.5

23.8

Series1

p=0.03

More patients achieved complete ST segment resolution in atorvastatin 80 mg Vs 10 mg group


STATIN- STEMI: ST resolution and MACE

Atorvastatin 80 mg is associated with:•Significantly better ST resolution•Trend for lower MACE

STATIN STEMI: Conclusion

High-dose atorvastatin pre-treatment before PCI improved immediate coronary flow after primary PCI compared with low-dose atorvastatin .


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

Hulten et al, Arch Intern Med 2006

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)

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

3252

30

30

3818

0%

20%

40%

60%

80%

100%

No Yes

STEMINSTEMIUnstable Angina

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.

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.

VIRHISTAMI Study

Objective: To evaluate effect of low Vs high-dose statin on necrotic core in coronary plaques as assessed by intravascular ultrasound - virtual histology87 STEMI patients were given low Or high dose statin for 12 months durationThe 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*

THE DURATION

• 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

Risk of CV event was inversely proportional to duration of atorvastatin 80 mg/day therapy



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



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

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

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 duration Trial duration

Statin treatmentStatin treatment

44,7

7,1

10,910,19,9

2,83,9

0

2

4

6

8

10

12

PCI no PCI PCI no PCI

Moderate (prava 40 mg)

Intensive (atorva 80 mg)

p 0.07p 0.07

p 0.01p 0.01

NSNS

NSNS

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

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

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<0.01n=56

P=0.18, log-rank

n=211

Statin therapy, inflammation and recurrent coronary events following PCI

Walter et al, J Am Coll Cardiol 2001;37:839

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:: 1822–1828 1822–1828Pasceri 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)

Statin No statin

OR 0.19OR 0.19 (95% CI 0.05-0.57) (95% CI 0.05-0.57)

p = 0.02OR 0.47OR 0.47 (95% CI 0.26–0.86) (95% CI 0.26–0.86)

p = 0.01

Peri

pro

ced

ura

l A

MI

(%)

7-day atorvastatin pretreatment decreases adhesion molecules after PCI

Patti et al, J Am Coll Cardiol 2006;48:1560

atorvastatinatorvastatin

placeboplacebo


5%5%

p 0.01p 0.01

17%17%

5%5%

p 0.01p 0.01

17%17%

Atorvastatin Pretreatment Improves Outcomes inPatients With ACS Undergoing Early PCI

ARMYDA-ACS Randomized Trial


Atorvastatin Pretreatment Improves Outcomes inPatients With ACS Undergoing Early PCI

Results of the ARMYDA-ACS Randomized Trial


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

Atorvastatin 80 mg placebo0

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):195-202High dose atorvastatin pre-treatment before PCI in STEMI patients significantly reduces CIN

THE MECHANISM

How can High dose statin produces immediate benefits in

STEMI?

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

Potential mechanisms by which statins act rapidly and favorably in ACS

Improve endothelial integrity & vasomotionDecrease plaque matrix degradation

Reduce plaque inflammationReduce platelet aggregability and thrombus

formationDecrease reperfusion injury

• 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)

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

• 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.

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

• 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).

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.

STATINSSTATINS↓LDL-C reduction

↑HDL-C Reduction in

chylomicron and

VLDL remnants,

IDL, LDL-CReduce plasma ViscosityReduce plasma ViscosityAltering platelet aggregationAltering platelet aggregationSuppressing ThrombinSuppressing ThrombinSuppress inflammation (↓ Suppress inflammation (↓ CRP/IL6) Inhibit M.M.P.CRP/IL6) Inhibit M.M.P.Improve Endothelial function Improve Endothelial function Up regulate Vasodilators Up 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 lipidlowering and anti-inflammatory effectslowering and anti-inflammatory effects

HIGH DOSE THE SIDE EFFECTS

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

StandarStandard dosed dose

High High dosedose


High High dosedose


High High 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%

A A to to 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%

RhabdomyolysisRhabdomyolysisCPK >10 xULNCPK >10 xULNAST/ALT >3 xULNAST/ALT >3 xULN

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.

Rate of Elevated Liver Enzymes by Statin Dose Rate 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

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.

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

Study Trial Population Regimens Duration (yrs)

New DM Cases inCompared Regimens

Relative LDLReduction

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% averagein trial

ALLHAT-LLT

CAD or CAD riskfactors

Pravastatin 40 mg 4.8 238 (7.9%) 18.1% at 24 mos

PROVE-IT-TIMI-22

Recent ACS Atorvastatin 80 mg vspravastatin 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 vssimvastatin 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

THE COMPLIACE

% STEMI patients receiving statin at discharge in India and developed countries

Kerala ACS registry NCDR action registry0

10

20

30

40

50

60

70

80

90

100

69

94.5

% S

TE

MI

pa

tie

nts

re

ce

ivin

g s

tati

n a

t d

isc

ha

rge

Circulation. 2011; 124: A9151

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

Difference in High dose statin use in STEMI and UA/NSTEMI in KOREA

STEMI NSTEMI/UA0

5

10

15

20

25

19.6

13.7

% p

ati

en

ts r

ec

eiv

ing

sta

tin

at

dis

ch

arg

e

Clin Cardiol. 2012 Nov;35(11):700-6

STEMI NSTEMI/UA0

5

10

15

20

25

20.1

12.2

% p

ati

en

ts r

ec

eiv

ing

sta

tin

at

dis

ch

arg

e

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

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 ILevel of Evidence B

ESC 2012 STEMI GUIDELINES

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

Conclusions

• Benefit of intensive statin therapy is

evident in ACS patients who

underwent PCI• Pleiotropic effects Pleiotropic 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 achieve Fixed doses / dose titration to achieve specific goals specific goals (lipid / anti-inflammatory)(lipid / anti-inflammatory)

Health & Medicine

14.09.13 high dose statin