recent advances in the management of unstable cardiac ... · • pharmacoinvasive approach safe and...

Recent Advances in the Management ofUnstable Cardiac Ischemic Syndromes

Elliot Rapaport, MDMonterey, CAMay 1, 2010

STRIVE ®

ACUTE CORONARY SYNDROMES

No ST elevation ST elevationUnstable angina NSTEMI STEMI

Spectrum of Acute Ischemic CAD

Figures reprinted with permission from Davies MJ. Heart. 2000;83(3):361-366.

Lloyd-Jones D, et al. Heart Disease and Stroke Statistics—2010 Update: A Report From the American Heart Association Circulation 2009 Dec 17 [Epub ahead of print]

Abbreviations: CAD, coronary artery disease; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.

~0.4 MillionDischarges Per Year

~1 MillionDischarges Per Year

Approach to Preventing the Consequences of a Vulnerable Plaque Rupture or Erosion

Manage the culprit lesion either invasively or conservatively based onquantifying the potential immediate and long term risk, with the primary goal of immediate (STEMI) or early (NSTEMI) restorationof maximum epicardial and microvascular coronary blood flow.

Utilize long term dual antiplatelet therapy of at least one year ( whether or not a PCI was done ) to minimize the potential of similar future episodes arising either from the same or other vulnerarble areas.

Insure maximum long term medical management as well as appropriate lifestyle changes to pacify other potential vulnerable plaques and to arrest the generalized progression of atherothrombosis.

Copyright ©2009 American Heart Association

Chan, M. Y. et al. Circulation 2009;119:3110-3117

Kaplan-Meier mortality curves of STEMI vs NSTEMI showing all-cause mortality from the time of cardiac catheterization

Mortality

Time ( years )

NSTEMI

STEMI

Management failuren=2399

n=1957

STRIVE ®

5

Effect of Door-to-Balloon Time on Mortality in Patients With STEMI

McNamara RL, et al. J Am Coll Cardiol. 2006;47(11):2180-2186.

8

7

6

5

4

3

2

1

0≤90 >90 - 120 >120 - 150 >150

Door-to-Balloon Time (min)

In-h

osp

ital

Mo

rtal

ity,

%

NRMI 3 and 4 ( 1999-2002)

STRIVE ®

6

Class I Modified Recommendations

Reperfusion Therapy for STEMI

• STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 minutes of first medical contact as a systems goal (Level of Evidence: A)

• STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI center and undergo PCI within90 minutes of first medical contact should be treated with fibrinolytictherapy within 30 minutes of hospital presentation as a systems goal unless fibrinolytic therapy is contraindicated (Level of Evidence: B)

Antman EM, et al. J Am Coll Cardiol. 2008;51(2):210-247.

2007 ACC/AHA STEMI Focused Update

STRIVE ®

7

Reperfusion Times

PrehospitalECG

(n=1941)

In-Hospital ECG

(n=5157)P value

Fibrinolytic agentsDTN time (min)a

DTN time ≤30 min

(n=72)19 (10, 30)

72

(n=167)29 (19, 45)

49.003.05

Primary PCI

DTB time (min)a

DTB time ≤90 min

(n=1501)

61 (46, 79)82

(n=3563)

75 (58, 95)70

<.0001<.0001

Timing of Reperfusion Therapy by Pre- versus In-Hospital ECG Utilization

Diercks DB, et al. J Am Coll Cardiol. 2009;53(2):161-166. (NCDR ACTION Registry)

STRIVE TM

TRANSFER-AMI

• Primary end point (death, MI, heart failure, severe recurrent ischemia, or shock at 30 days): 10.6% in pharmacoinvasive arm vs 16.6% in standard treatment arm (P=.0013)

• Reinfarction: 3.3% vs 6.0% (P=.044)

• Recurrent ischemia: 0.2% vs 2.2% (P=.02)

Preliminary Results

Conclusions

(P=.0013)

Pharmacoinvasivestrategy(n=522)

Standard therapy(n=508)

Primary End Point• Pharmacoinvasive approach safe and

efficacious compared with treatment with thrombolytics and transfer for rescue PCI only. No excess in major bleeding

• Optimal window: 6 hours

0

10

20

% 10.6

16.63.7 3.6

%

0

1

5

2

3

4

Mortality

(P=.94)

Trial design: Patients with high-risk STEMI who presented where timelyPrimary PCI was not feasible were randomized to a pharrmacoinvasive(ASA, TNK, UFH or Enox, clopidogrel strategy with emergent transfer for PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis

Cantor W,. N. Engl. J. Med. 360 (26):2705-18. Cantor W,. N. Engl. J. Med. 360 (26):2705-18.

n=133n=133 n=125n=125

Halvorsen S.ESC 2009 Congress;Barcelona, Spain.

TNK to 1TNK to 1stst balloon 3.0 d (0,13)balloon 3.0 d (0,13)

TNK to 1TNK to 1stst balloon 163m (137,191)balloon 163m (137,191)

STRIVE ®

2009 STEMI Focused Update ( New Recommendations )

Class IIa

In STEMI patients undergoing PCI who are at high risk of bleeding,Bivalirudin anticoagulation is reasonable.

It is reasonable for high risk patients who receive fibrinolytic therapyas primary reperfusion therapy at a non-PCI capable facility to be transferred as soon as possible to a PCI-capable facility where PCI can be performed either when needed or as a pharmacoinvasivestrategy. Consideration should be given to initiating a preparatory antithrombotic (anticoagulant plus antiplatelet) regimen before andduring patient transfer to the catheterization laboratory.

It is reasonable to use an insulin-based regimen to achieve and Maintain glucose levels less than 180 mg/dL while avoiding hypoglycemia for patients with STEMI with either a complicatedor uncomplicated course.

Kushner FG, et al. J Am Coll Cardiol. 2009;54(23):2205-2241.

STRIVE TM

0.1 0.5 1 2 5

Favors Invasive

Favors Conservative

Odds Ratio Death or MI

OR 0.82, P<.0012.2% abs reduction

Trial (N)

TIMI IIIB (1473)

VANQWISH (920)

MATE (201)

FRISC II (2457)

TACTICS (2220)

RITA 3 (1810)

Total (N = 9212)

Invasive Management of UA/NSTEMI Meta-analysis: Death/MI at End of Follow-up (Mean 17.3 months)

11.6 13.8

32.9 30.3

14.4 12.2

10.4 14.1

7.3 9.5

10.6 12.9

VINO (131) 6.3 22.4

Inv (%) Cons (%)

12.2 14.4

Mehta S, et al. JAMA. 2005;293:2908-2917.

Acute care patterns by early invasive management*

Bhatt et al. JAMA 2004;292:2096

No early invasive care(n=9889)

Early invasive care(n=8037) p value

Aspirin 87.7% 93.8% <0.001

Clopidogrel 26.1% 51.3% <0.001

B blocker 71.9% 77.7% <0.001

Heparin 73.7% 88.8% <0.001

GP IIb/IIIainhibitor 14.2% 50.9% <0.001

Bhatt et al. JAMA 2004;292:2096

STRIVE ®

14

%

4.96.0

TIMACS

No difference in primary outcome (death, MI, stroke) between the two arms (HR, 0.85; 95% CI, 0.68-1.06; P= .15), except in high-risk patients (GRACE risk score >140) (HR, 0.65; 95% CI, 0.48-0.88; P = .005)

Death, MI, refractory ischemia ↓ in early invasive arm (P = .0002), due to ↓ in refractory ischemia (P <.0001); death (P = .19), stroke (P = .74) similar

Major bleeding was similar (P = .53)

Trial design: Patients with NSTEMI were randomized to an early (within 24 hours) or delayed (after 36 hours) invasive strategy. Clinical outcomes were compared at 6 months.

Results

Conclusions An early invasive strategy (within 24 hours) is not

associated with harm compared with a delayed invasive strategy (after 36 hours) in patients with NSTEMI, and may be beneficial in high-risk patients

Significant reduction in refractory ischemia with an early invasive strategy

Mehta SR, et al. : American Heart Association 2008 Scientific Sessions

(P = .15)

Early invasive(n = 1593)

Delayed invasive(n = 1438)

(P = .19)20

15

10

5

0

9.711.4

Primary end point Mortality

%

20

15

10

5

0

Trial design: Patients with NSTEMI were randomized to an early (within 24 hours) or delayed (after 36 hours) invasive strategy. Clinical outcomes were compared at 6 months. Trial design: Patients with NSTEMI were randomized to an early (within 24 hours) or

delayed (after 36 hours) invasive strategy. Clinical outcomes were compared at 6 months.

Preliminary Results

ABOARD study designABOARD study designABOARD study design

NSTENSTE--ACS ( n = 352 )ACS ( n = 352 )2 of 3 Criteria: Ischemic symptom, ST2 of 3 Criteria: Ischemic symptom, ST--T change, troponin riseT change, troponin rise

with TIMI score with TIMI score >> 33

Immediate cathImmediate cath Next day cathNext day cath

All PCIs on abciximabAll PCIs on abciximab

11--month Followmonth Follow--upup

IVRS RANDOMIZATIONIVRS RANDOMIZATION

JAMA 2009;302:947-954

Preliminary Results

Composite Ischemic Endpoints at 1 monthComposite Ischemic Endpoints at 1 month

%%

0

5

10

15

20

25

Death / MI / UR Death / MI / UR / RI

ImmediateDelayed

Key secondary EP

P=0.31

P=0.94

JAMA 2009;302:947-954

STRIVE TM

Optimal Timing for Pretreatment With Clopidogrel 300 mg Before PCI: CREDO Study

Steinhubl SR, et al. J Am Coll Cardiol. 2006;47(5):939-943.

For pretreatment ≥15 h vs placebo, P=.018; for pretreatment ≥15 h vs <15 h, P=.033; for placebo vs pretreatment <15 h, P=.72.

10

8

6

4

2

00 5 10 15 20 25

Dea

th, M

I, U

TV

R, %

Days

Placebo Pretreatment (n=915)

Clopidogrel Pretreatment <15 hours (n=645)

Clopidogrel Pretreatment ≥15 hours (n=202)

3.5%

7.8%8.3%

Pts randomize to receive study drug or placebo between 3 and 24 hours before PCI

STRIVE ®

1818

ARMYDA-ACS: Design and Primary End PointPrimary end point: death, MI,

or unplanned revasc. at 30 days

P=.01

5%

0%

5%

10%

15%

Atorvastatin Placebo

17%

Atorvastatin80 mg 12hbefore PCI;

additional 40 mg2h before PCI

(N=86)

Placebo 12h before PCI;

additional dose 2h before PCI

(N=85)

Patients with NSTE-ACSsent to early PCI

(<48 hours). Statin naïve patients

Randomization(N=171)

Patti G, et al. J Am Coll Cardiol. 2007;49(12):1272-1278.

All patients given clopidogrel 600 mg loading dose; long-term atorvastatin

(40 mg/d)

20%

UA/NSTEMI Strategy OverviewUA/NSTEMI Strategy OverviewUA/NSTEMI Strategy Overview

ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, 6, 2007, Circulation.Circulation.

2007 ACC/AHA UA/NSTEMI Guideline Revision

EARLY INVASIVE VS. INITIAL CONSERVATIVE THERAPY

“In initially stabilized patients, an initially conservative (i.e., a selectively invasive) strategy may be considered as a treatment strategy for UA/NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events, including those who are troponin positive.” (Class IIb) “The decision to implement an initial conservative (vs. initial invasive) strategy in these patients may be made by considering physician and patient preference.” (Class IIb)


EARLY INVASIVE VS. INITIAL CONSERVATIVE THERAPYEARLY INVASIVE VS. INITIAL CONSERVATIVE THERAPY

““In initially stabilized patients, an In initially stabilized patients, an initially conservative (i.e., a initially conservative (i.e., a selectively invasive) strategy may be consideredselectively invasive) strategy may be considered as a treatment as a treatment strategy for UA/NSTEMI patients (without serious strategy for UA/NSTEMI patients (without serious comorbiditiescomorbidities or or contraindications to such procedures) who have an elevated risk contraindications to such procedures) who have an elevated risk for for clinical events, clinical events, including those who are including those who are troponintroponin positivepositive..”” (Class (Class IIbIIb) ) ““The decision to implement an initial conservative (vs. initial The decision to implement an initial conservative (vs. initial invasive) strategy in these patients may be made by invasive) strategy in these patients may be made by considering considering physician and patient preferencephysician and patient preference..”” (Class (Class IIbIIb))

Cumulative risk of CV death or MI by risk groupCumulative risk of CV death or MI by risk group

High

Intermediate

Low

11.1% abs. risk reduction

3.8% abs RR

2% abs RR

““A A conservative strategyconservative strategy is recommended in is recommended in women with lowwomen with low--risk features (I, B)risk features (I, B)””


EARLY INVASIVE VS. INITIAL CONSERVATIVE THERAPYEARLY INVASIVE VS. INITIAL CONSERVATIVE THERAPY

Meta analysis – Death in women

Study name Dead / Total Statistics for each study Odds ratio and 95% CI

Routine Selective Odds Lower Upper Invasive Invasive ratio limit limit p-Value

FRISC II 14 / 348 13 / 401 1.25 0.58 2.70 0.57

RITA 3 18 / 350 8 / 332 2.20 0.94 5.12 0.07

TACTICS 15 / 395 13 / 362 1.06 0.50 2.26 0.88

OASIS 5 8 / 92 1 / 92 8.67 1.06 70.77 0.04

55 /1185 35 /1187 1.50 0.96 2.35 0.07

0.01 0.1 1 10 100

Favours Early Invasive Favours Selective Invasive

STRIVE ®

23

Adjunctive Thrombectomy and Embolic Protection Devices in AMI: Meta-analysisa

P=.018

P=.050

Mo

rtal

ity,

%

P=.69

Bavry AA, et al. Eur Heart J. 2008;29(24):2989-3001.

2.7

5.3

4.4

2.8 3.1

0

3

6

Catheter thrombusaspiration

Mechanical thrombectomy

Embolic protection

Adjunctive device prior to PCI

PCI alone

3.4

a Meta-analysis of 30 randomized clinical trials with 6415 patients.

Sites of Anticoagulant and Sites of Anticoagulant and AntiplateletAntiplatelet Drug ActionDrug Action

Tissue factorTissue factor

Plasma clottingcascade

Plasma clottingcascade

ProthrombinProthrombin

ThrombinThrombin

FibrinogenFibrinogen FibrinFibrin

ThrombusThrombus

Platelet aggregationPlatelet aggregation

Platelet activationPlatelet activation

CollagenCollagen

Thromboxane A2Thromboxane A2

ADPADP

ATAT

ATAT

Aspirin

ClopidogrelPrasugrelCangrelorTicagrelor

EptifibatideAbciximabTirofiban

Bivalirudin

FactorXa

FactorXa

Heparin Enoxaparin

Fibrinolytics

Fondaparinux

ATAT

SCH 530348

STRIVE ®

25

ARMYDA-2 Study: Design and Primary End Point

Primary composite of death, MI, or target vessel revasc. at 30 days

P=.041

4%

0%

2%

4%

6%

8%

10%

12%

14%

600 mg 300 mg

12%

High Loading Dose of

Clopidogrel600 mgPre-PCI

Standard Loading Dose

of Clopidogrel

300 mgPre-PCI

255 patients with stable CAD or NSTEMI prior to PCI

13% received GP IIb/IIIa inhibitors20% received drug-eluting stents

Randomized 4-8 Hours Pre-PCI

ARMYDA-2, Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty.

Patti G, et al. Circulation. 2005;111(16):2099-2106.

STRIVE TM

26

Clopidogrel High-Dose GroupClopidogrel 600 mg loading dose day 1 followed by 150 mg from days 2 to 7; 75 mg from days 8 to 30

Clopidogrel Standard-Dose GroupClopidogrel 300 mg (+ placebo) day 1 followed

by 75 mg (+ placebo) from days 2 to 7;75 mg from days 8 to 30

Patients with UA or MI planned for early invasiveStrategy (PCI intended as early as possible within 24 h)

RANDOMIZE

Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS-7

CURRENT/OASIS-7

RANDOMIZERANDOMIZE

ASA low-dose groupAt least 300 mg day 1;

75–100 mgfrom days 2 to 30

ASA high-dose groupAt least 300 mg day 1;


ASA high-dose groupAt least 300 mg day 1;


ASA low-dose groupAt least 300 mg day 1;


.

Mehta SR. Eur Heart J Suppl. 2006;8:G25-G30.

Primary Outcome: 30-day CV Death, MI, or Recurrent Ischemia

Days

Cu

mu

lati

ve H

aza

rd

0.0

0.01

0.02

0.03

0.04

0 3 6 9 12 15 18 21 24 27 30

Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients

Clopidogrel Standard

Clopidogrel Double

HR 0.8595% CI 0.74-0.99

P=0.036

15% RRR15% RRR

CV Death, MI or StrokeCV Death, MI or Stroke

ECC Aug 30, 2009

Clopidogrel HR 95% CI P P int’n

Standard Double

CV Death/MI/Stroke (Overall)

ASA High 4.6 3.8 0.83 0.70-0.99 0.0360.043ASA Low 4.2 4.5 1.07 0.91-1.27 0.42

MI/Stent Thrombosis (PCI pts)

ASA High 3.8 2.7 0.71 0.56-0.90 0.005 0.19

ASA Low 3.6 3.2 0.89 0.71-1.12 0.32

Major Bleed (Overall)

ASA High 2.2 2.4 1.08 0.86-1.37 0.510.099

ASA Low 1.9 2.7 1.43 1.13-1.81 0.003

Clopidogrel: Double vs Standard Dose byASA Factorial

ECC Aug 30, 2009

Active Metabolite Formation:Prasugrel and Clopidogrel

Active Metabolite Formation:Prasugrel and Clopidogrel

Main trial design

Double-blind

ACS (STEMI or UA/NSTEMI) and planned PCI

ASA

PRASUGREL60 mg LD/ 10 mg MD

CLOPIDOGREL300 mg LD/ 75 mg MD

1o end point: CV death, MI, stroke2o end point: Stent thrombosis Safety end points: TIMI major bleeds, life-threatening bleeds

Duration of therapy: 6-15 months

N = 13,608

TRITON TIMI-38

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)P = 0.0004Prasugrel

Clopidogrel

Days

En

d P

oin

t (%

)

12.1

9.9

HR 1.32(1.03-1.68)

P = 0.03

Prasugrel

Clopidogrel1.82.4

TRITON TIMITRITON TIMI--38: Primary results38: Primary results

CV death/MI/stroke

TIMI major NonCABG bleeds

Bleeding Events: Safety CohortClop, % Pras, % P

TIMI major 1.8 2.4 .03Life threatening 0.9 1.4 .01Nonfatal 0.9 1.1 .23Fatal 0.1 0.4 .002ICH 0.3 0.3 .74

Efficacy

Safety

TRITON TIMI-38 STEMI cohort

Montalescot et al. ESC 2008

Efficacy endpoints at 15 months

Clopidogrel

Prasugrel

0

2

4

6

8

10

12

14

p= 0.11

p= 0.02

p= 0.09p= 0.02

p= 0.007 p= 0.03 p= 0.02

Pro

po

rtio

n o

f p

op

ula

tio

n (

%)

All Death MI UTVR StentThrombosis*

CV Death/MI

CV Death/MI/UTVR

CV Death/MI/Stroke

* ARC def/probable

No increase in TIMI major or minor non-CABG bleeding was observed

I IIa IIb III

STRIVE ®

33

C


Thienopyridines

2009 ACC/AHA STEMI/PCI Guidelines Focused Updates

New RecommendationClass 3

2009 ACC/AHA STEMI and PCI Guidelines Focused Updates

In STEMI patients with a prior history of stroke and transient ischemic attack for whom primary PCI is planned, prasugrel is not recommended as part of a dual- antiplatelettherapy regimen

Hazard Ratio 1.53

(95% CI 1.07-2.19)

P=0.014

8.0

12.1

1064 1009 999 980 870 755 542

Number at Risk:

Days After Randomization

Non-Carrier

395 364 360 348 306 270 181Carrier

CV

Death

, M

I, o

r S

troke (

%)

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0 30 90 180 270 360 450

Non-carriers

Carriers

CYP2C19 and CVD, MI, or StrokeCLOPIDOGREL

* Carriers ~30% of the population

CYP2C19 Reduced-Function Allele Carriers

N=1,477

Hazard Ratio 0.89

(95% CI 0.60-1.31)

P=0.27

9.8

8.5

1048 991 982 951 849 750 541

407 383 376 364 320 276 188

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0 30 90 180 270 360 450

Number at Risk:

Days After Randomization

Non-Carrier

Carrier

CV

Deat

h, M

I, or

Str

oke

(%

) Non-carriers

CarriersCYP2C19Reduced-Function

Allele Carriers

PRASUGREL

N=1,466

Pharmacogenetics of antiplatelet therapy

Mega et al. NEJM 2009

InvasivePLATO study design

6–12 months treatment

PCI = percutaneous coronary intervention; CV = cardiovascular; PI = principal investigator

NSTEMI ACS (moderate-to-high risk) STEMI (if primary PCI) (N=18,624)Clopidogrel-treated or -naive; randomized <24 hours of index event

At randomization, 13,408 (72%) of patients were specified by the Investigator: intent for invasive strategy

Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding

Clopidogrel (n=6,676)If pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,

then 75 mg qd maintenance;(additional 300 mg allowed pre-PCI)

Ticagrelor (n=6,732)180 mg loading dose, then

90 mg bid maintenance;(additional 90 mg pre-PCI)

InvasivePrimary endpoint: CV death, MI or stroke

0

0

5

10

15

60 120 180 240 300 360

Days after randomization

K-M

es

tim

ate

d r

ate

(%

pe

r ye

ar)

HR: 0.84 (95% CI = 0.75–0.94), p=0.0025

9.02

10.65Clopidogrel

Ticagrelor

No. at risk

Clopidogrel

Ticagrelor

6,676

6,732

6,129

6,236

6,034

6,134

5,881 4,815

4,889

3,680

3,735

2,965

3,0485,972

HR 0.99 (95% CI = 0.89–1.10), p=0.88 for major bleeding

No. at risk

Clopidogrel

Ticagrelor

9,291

9,333

8,560

8,678

8,405

8,520

8,177

Days after randomisation

6,703

6,796

5,136

5,210

4,109

4,191

0 60 120 180 240 300 360

6

5

4

3

2

1

0

7

Cu

mu

lati

ve i

nc

ide

nc

e (

%)

Clopidogrel

Ticagrelor

5.8

6.9

8,279

HR 0.84 (95% CI 0.75–0.95), p=0.005

0 60 120 180 240 300 360

6

4

3

2

1

0

Clopidogrel

Ticagrelor

4.0

5.1

HR 0.79 (95% CI 0.69–0.91), p=0.001

7

5

9,291

9,333

8,865

8,294

8,780

8,822

8,589

Days after randomisation

7079

7119

5,441

5,482

4,364

4,4198,626

Myocardial infarction Cardiovascular death

Cu

mu

lati

ve i

nc

ide

nc

e (

%)

Secondary efficacy endpoints over time

MortalityMortality

Major BleedingMajor Bleeding

TransfusionTransfusionHypotensionHypotension Cessation of Cessation of ASA/ASA/ClopidogrelClopidogrel

IschemiaIschemia Stent ThrombosisStent Thrombosis InflammationInflammation

Bhatt DL et al. In Braunwald: Harrison’s Online 2005.

Possible Relationship BetweenPossible Relationship BetweenBleeding and Mortality in ACSBleeding and Mortality in ACS

I IIa IIb III

STRIVE ®

39

The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part of a preparatory pharmacologic strategy for patients with STEMI prior to arrival in the cardiac catheterization laboratory for angiography) is uncertain


Use of GP IIb/IIIa Inhibitors in STEMI

2009 ACC/AHA STEMI/PCI Guidelines Focused Updates

Modified RecommendationClass 2b

2009 ACC/AHA STEMI and PCI Guidelines Focused Updates

1-Year Mortality (All-Cause)

Number at riskBivalirudin aloneHeparin+GPIIb/IIIa

1800 1705 1684 1669 15201802 1679 1664 1647 1487

Mo

rtal

ity

(%)

0

1

2

3

4

5

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

Bivalirudin alone (n=1800)

Heparin + GPIIb/IIIa (n=1802) 4.8%

3.4%

Diff [95%CI] =

-1.4% [-2.7,-0.1]

HR [95%CI] =

0.70 [0.51, 0.98]

P=0.036P=0.036

3.1%

2.1%

Δ = 1.0%

P=0.049

Δ = 1.4%

STRIVE TM

Immediate Pharmacotherapy for STEMI Patient

Managed by Primary PCI

Aspirin

Start anticoagulant in ED

IV Morphine as needed for analgesia

Sublingual NTG followed by IV Drip

If enoxaparin or UFH started, switch to IV Bolus

of bivalarudin once PCI begun. If procedure lasting

longer than 30 minutes start bivalarudin infusion

If bivalarudin not used, consider adding a GP 2b/3a inhibitor,

clopid. 600 mg or Prasugrel 60 mg after angio confirms PCI need

STRIVE TM

Initial Invasive Strategy: Antiplatelet, Anticoagulant Therapy

Aspirin Initiate anticoagulant therapy as soon as possible after

presentation (I, A). Regimens with established efficacy:– Enoxaparin or UFH (I, A)– Bivalirudin or fondaparinux (I, B)

Prior to angiography, initiate one (I, A) or both (IIa, B)– Clopidogrel– IV GP IIb/IIIa inhibitor

Use both if: Delay to angiography High-risk features Early recurrent ischemic syndromes


Anderson JL, et al. J Am Coll Cardiol. 2007;50(7):e1-e157.

STRIVE TM

Secondary Prevention: Additional Recommendations

β-blockers

ACE inhibitors/ARBs

Aldosterone blockade

Lipid management– Statin regardless of

baseline LDL-C initiated prior to discharge

– Goal LDL-C <100 mg/dL

– LDL <70 mg/dLreasonable

Treatment of triglycerides and non–HDL-C useful

– If TG 200-499 mg/dL, non–HDL-C should be <130 mg/dL

– TG 500 mg/dL, fibrate or niacin before LDL-C lowering to prevent pancreatitis

Encouraging consumption of omega-3 fatty acids for risk reduction reasonable

– For treatment of elevated triglycerides, higher doses may be used for risk reduction



STRIVE TM

Secondary Prevention: Additional Recommendations (cont)

BP control

– <140/90 mm Hg

– <130/80 mm Hg with diabetes or CKD

Diabetes management: HbA1c<7%

Smoking cessation/no environmental smoke exposure

– Education, referral programs, drug therapy

Physical activity (30-60 min, 7 d/wk; min 5 d/wk)

Weight management

– BMI 18.5-24.9 kg/m2

– Waist circumference: men, <40 in; women, <35 in

Discharge education/referral

Stepped-care approach to musculoskeletal pain management

Annual influenza immunization

HRT, antioxidant vitamin supplements (C, E, beta carotene) and folic acid not recommended



recent advances in the management of unstable cardiac ... · • pharmacoinvasive approach safe and...

Documents