Welcome Ask The Experts March 24-27, 2007 New Orleans, LA

Welcome Welcome Ask The ExpertsAsk The Experts

March 24-27, 2007March 24-27, 2007

New Orleans, LANew Orleans, LA

Incorporating Patient Risk into Incorporating Patient Risk into Decisions Regarding the Optimal Decisions Regarding the Optimal

Reperfusion Strategy for ST Reperfusion Strategy for ST Elevation MIElevation MI

Duane S. Pinto, MDAssistant Professor of Medicine

Harvard Medical SchoolDirector, Cardiology Fellowship Training Program

Beth Israel Deaconess Medical CenterBoston, MA

Harvard Medical School

PAMIPAMIPAMIPAMI

2.6 2.6

5.1

0

6.5

10.4

6.5

12

22.0

0

2

4

6

8

10

12

14

Mortality Mortality(high-risk)

Reinfarction Reinfarctionor death

Stroke

PTCAtPA

(Grines et al. N Engl J Med 1993;328:673)(Grines et al. N Engl J Med 1993;328:673)


GUSTO IIbGUSTO IIbGUSTO IIbGUSTO IIb

7 6.5

0.9

13.6

5.74.4

1.2

9.6

0

2

4

6

8

10

12

14

16

Death Reinfarction Stroke Combined

tPAPTCA

29%

(N Engl J Med 1997; 336: 1621)(N Engl J Med 1997; 336: 1621)


74.5

2.2

6

1 0

7 897 7

21

2 1

5

13

0

5

10

15

20

25

30

35

PCI PCI

Fre

qu

en

cy (

%)

Fre

qu

en

cy (

%)

P=0.0002P=0.0002

P=0.0003P=0.0003 P < 0.0001P < 0.0001

P < 0.0001P < 0.0001

P < 0.0001P < 0.0001

P=0.0004P=0.0004

P=0.032P=0.032

P < 0.0001P < 0.0001

DeathDeath Death, Death, no no

SHOCKSHOCKdatadata

ReMIReMI Rec.Rec.IschemiaIschemia

Total Total StrokeStroke

Hem.Hem.StrokeStroke

Major Major BleedBleed

DeathDeathMIMI

CVACVA

Fibrinolysis Fibrinolysis

N = 7739N = 7739

Keeley E. et al., Keeley E. et al., LancetLancet 2003; 361:13-20. 2003; 361:13-20.

PCI vs Fibrinolysis for STEMI:PCI vs Fibrinolysis for STEMI:Short Term Clinical OutcomesShort Term Clinical Outcomes


Importance of Rapid Time toImportance of Rapid Time to Treatment With Treatment With FibrinolysisFibrinolysis in STEMI in STEMI

Importance of Rapid Time toImportance of Rapid Time to Treatment With Treatment With FibrinolysisFibrinolysis in STEMI in STEMI

Time from onset of symptoms to treatment (hours)Time from onset of symptoms to treatment (hours)

Abs

olut

e %

diff

eren

ce

Abs

olut

e %

diff

eren

ce

in m

orta

lity

at 3

5 da

ysin

mor

talit

y at

35

days 3.5% 3.5%

2.5% 2.5%

1.8%1.8% 1.6% 1.6%

0.5% 0.5% 0.00.0

1.01.0

3.03.0

2.02.0

4.04.0

0 – 10 – 1 2 – 32 – 3 4 – 64 – 6 7 – 127 – 12 12 – 2412 – 24

The Fibrinolytics Therapy Trialists’ collaborative group. The Fibrinolytics Therapy Trialists’ collaborative group. LancetLancet. 1994; 343:311. . 1994; 343:311.


1.14 1.151.41

1.62 1.61

0.2

0.6

1

1.4

1.8

2.2

0-60 61-90 91-120 121-150 151-180 >180

1.14 1.151.41

1.62 1.61

0.2

0.6

1

1.4

1.8

2.2

0-60 61-90 91-120 121-150 151-180 >180

NRMI 2: Primary PCI NRMI 2: Primary PCI Door-to-Balloon Time vs. MortalityDoor-to-Balloon Time vs. Mortality

NRMI 2: Primary PCI NRMI 2: Primary PCI Door-to-Balloon Time vs. MortalityDoor-to-Balloon Time vs. Mortality

Door-to-Balloon Time (minutes)Door-to-Balloon Time (minutes)

MV

Ad

just

ed O

dd

s o

f D

eath

MV

Ad

just

ed O

dd

s o

f D

eath

P=0.01 P=0.0007 P=0.0003

n = 2,230n = 2,230 5,7345,734 6,6166,616 4,4614,461 2,6272,627 5,4125,412

Cannon CP, JAMA 2000Cannon CP, JAMA 2000


Symptom – balloon inflation (min)Symptom – balloon inflation (min)

On

e-ye

ar m

ort

alit

y, %

On

e-ye

ar m

ort

alit

y, %

6 RCTs of Primary PCI by Zwolle Group 1994 – 20016 RCTs of Primary PCI by Zwolle Group 1994 – 2001N = 1791N = 1791

RR = 1.08 for each 30 min delayRR = 1.08 for each 30 min delay((PP = 0.04) = 0.04)

PP < 0.0001 < 0.000112

10

8

6

4

2

00 60 120 180 240 300 360

Symptom Onset-Balloon Time and Symptom Onset-Balloon Time and Mortality in Primary PCI for STEMIMortality in Primary PCI for STEMI

DeLuca, Suryapranata, Circ 109:1223, 2004DeLuca, Suryapranata, Circ 109:1223, 2004

The relative risk of 1-year mortality increases by7.5% for each 30-minute delay


Time from Symptom Onset to TreatmentTime from Symptom Onset to TreatmentPredicts One-year Mortality with PCIPredicts One-year Mortality with PCI

4.4

1.5

5.74.7

1.2

6.3

8.5

0.8

11.9

9.7

0.0

13.0

0

3

6

9

12

15

4.4

1.5

5.74.7

1.2

6.3

8.5

0.8

11.9

9.7

0.0

13.0

0

3

6

9

12

15 p = 0.006p = 0.006

<2 hrs<2 hrs 2-4 hrs2-4 hrs 4-6 hrs4-6 hrs

p = 0.02p = 0.02

De Luca at al, JACC 2003De Luca at al, JACC 2003

>6 hrs>6 hrs

All PatientsAll Patients Low-RiskLow-Risk

p = NSp = NS

High-RiskHigh-Risk


PCI-Related Time Delay vs Mortality PCI-Related Time Delay vs Mortality BenefitBenefit

in 22 Randomized Studies of PCI vs in 22 Randomized Studies of PCI vs Fibrinolytic TherapyFibrinolytic Therapy



-5

0

5

10

15

Ab

solu

te R

isk

Diff

ere

nce

In

Dea

th (

%)

0 20 40 60 80 100PCI-Related Time Delay (min)

Nallamothu and Bates, AJC 2003Nallamothu and Bates, AJC 2003

23 RCTsFor every 10 min delay to PCI:

1 % reduction in Mortality Difference Between PCI & LysisN= 7419

p=0.006






Betriu A, Massotti M. Am J Cardiol. 2005. 100-101Betriu A, Massotti M. Am J Cardiol. 2005. 100-101


0.24 % reduction in Mortality Difference Between PCI & LysisN= 7350


PCAT-2 AnalysisPCAT-2 AnalysisPCAT-2 AnalysisPCAT-2 Analysis

Patient level data included in analysis of 22 Patient level data included in analysis of 22 trials (n=6,763)trials (n=6,763)

PPCI was associated with a PPCI was associated with a 67%67% reduction in odds of death at 30 days if PCI reduction in odds of death at 30 days if PCI

related delay was related delay was <35 minutes<35 minutes Only Only 28%28% if if >35 minutes>35 minutes (p=0.004) (p=0.004)

Boersma E. EHJ. 2006; 27: 779-788.Boersma E. EHJ. 2006; 27: 779-788.


Advantage of PCI Compared With Fibrinolysis Advantage of PCI Compared With Fibrinolysis Decreases as PCI-Related Delay IncreasesDecreases as PCI-Related Delay Increases

Advantage of PCI Compared With Fibrinolysis Advantage of PCI Compared With Fibrinolysis Decreases as PCI-Related Delay IncreasesDecreases as PCI-Related Delay Increases

Pinto DS, et al. Pinto DS, et al. CirculationCirculation. 2006;114:2019-2025.. 2006;114:2019-2025.

*Betriu A. Am J Cardiol. 2005; 95:100-101.*Betriu A. Am J Cardiol. 2005; 95:100-101.

Od

ds

of

Dea

th W

ith

O

dd

s o

f D

eath

Wit

h

Fib

rin

oly

sis

Fib

rin

oly

sis

PCI-Related Delay (door-to-balloon–door-to-needle time), minPCI-Related Delay (door-to-balloon–door-to-needle time), min

PC

I B

ett

er

PC

I B

ett

er

Fib

rin

oly

sis

Be

tte

rF

ibri

no

lys

is B

ett

er

2.02.0

1.51.5

1.251.25

1.01.0

0.80.8

0.50.56060 7575 9090 105105 114114 135135 150150 165165 180180

Randomized Studies*Randomized Studies*


PCI Related Delay (DB-DN) Where PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal PCI and Fibrinolytic Mortality Are Equal

(Min)(Min)Stratified by Patient CharacteristicsStratified by Patient Characteristics

PCI Related Delay (DB-DN) Where PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal PCI and Fibrinolytic Mortality Are Equal

(Min)(Min)Stratified by Patient CharacteristicsStratified by Patient Characteristics

PC

I R

elat

ed D

elay

(D

B-D

N)

(Min

)P

CI

Rel

ated

Del

ay (

DB

-DN

) (M

in)

68,71668,716 123,793123,793

94

190

115 112

155

71

114

0

60

120

180

240

125,737125,737 66,77266,772 69,33169,331 123,178123,178 115,293115,29377,14177,141 192,509192,509

<120<120 120+120+ ANTANT NonAntNonAnt 65+65+ <65<65

Prehospital Delay (min)

Infarct Location

Age (years)

All Patients

Prehospital Delay (min)

Infarct Location

Age (years)

All Patients

P<0.05 for all 2 way comparisonsP<0.05 for all 2 way comparisons

Pinto DS, et al. Pinto DS, et al. CirculationCirculation. 2006;114:2019-2025.. 2006;114:2019-2025.


Meta-analysis of Transfer for PCI vs. Meta-analysis of Transfer for PCI vs. FibrinolysisFibrinolysis

Meta-analysis of Transfer for PCI vs. Meta-analysis of Transfer for PCI vs. FibrinolysisFibrinolysis

Dalby M, et al. Circ 2003; 1809Dalby M, et al. Circ 2003; 1809

2% beneficial survival rate with PPCI 2% beneficial survival rate with PPCI with PCI related time delay of 65 with PCI related time delay of 65

minutesminutes


De

ath

/MI/S

tro

ke

(%)

De

ath

/MI/S

tro

ke

(%)

DANAMI-2: Primary ResultsDANAMI-2: Primary Results

LyticLytic Primary PCIPrimary PCI

PP=0.0003=0.0003CombinedCombined

00

44

1212

1616

88

1414

88

RRRRRR45%45%


PP=0.002=0.002Transfer SitesTransfer Sites

00

44

1212

1616

88

1414

99

RRRRRR40%40%


PP=0.048=0.048Non-Transfer SitesNon-Transfer Sites

00

44

1212

1616

88 77

1212RRRRRR45%45%


Transportation= 32 min

DANAMI-2

Invasive

Referral

Invasive

Referral

Minutes

Hospitals

Fibr

inol

ysis

PCI

26 min

0 60 120 180 240

Door-to-balloon

Door-to-needle

Door-to-balloonIn-door-out-door

Prehospital

Prehospital

Prehospital

Door-to-needlePrehospital

↑ Randomization-balloon = 90 min

Door-balloon = 93 min

45 min

50 min


Maybe Our Systems Are Not Maybe Our Systems Are Not Completely Completely Optimized in the US!Optimized in the US!

Maybe Our Systems Are Not Maybe Our Systems Are Not Completely Completely Optimized in the US!Optimized in the US!


DANAMI vs US AMI: DANAMI vs US AMI: Are We As Quick in the US?Are We As Quick in the US?

Pinto DS, et al. Pinto DS, et al. Cardiovascular Reviews and Report.Cardiovascular Reviews and Report. 2003;24:267-276. 2003;24:267-276.

0

Med

ian

Tim

e (m

in)

Med

ian

Tim

e (m

in)

DANAMIOn-Site Primary PCI

DANAMIOn-Site Primary PCI

DANAMITransfer Primary PCI

DANAMITransfer Primary PCI

US AMITransfer Primary PCI

US AMITransfer Primary PCI

90

110

185

50

100

150

200

225

25

75

125

175


Times in Randomized Trials vs. the “Real World”Times in Randomized Trials vs. the “Real World”Times in Randomized Trials vs. the “Real World”Times in Randomized Trials vs. the “Real World”

BK Nallamothu, ER Bates, HM Krumholz, et al. Circulation 2005; 761 BK Nallamothu, ER Bates, HM Krumholz, et al. Circulation 2005; 761

Median Door to Balloon Time: 180 min

Median Door to Door (Transfer) Time: 120 Min

Median PCI Hospital DB time: 53 Min

<5% of patients had Total DB time <90 Min if a transfer was involved

Compare this to the randomized studies with: Total DB times of 90 min, Transport times of 30 min, and PCI hospital DB times of 25 min






-5

0

5

10

15

Ab

solu

te R

isk

Diff

ere

nce

In

Dea

th (

%)

0 20 40 60 80 100PCI-Related Time Delay (min)

Nallamothu and Bates, AJC 2003Nallamothu and Bates, AJC 2003


1 % reduction in Mortality Difference Between PCI & LysisN= 7419

p=0.006

DANAMI: on site PCI

90 DB – 50 DN = 40 min delay

DANAMI: with transfer


“USA AMI” with transfer:

171 DB – 32 DN =

139 min delay

DANAMI: on site PCI


DANAMI: with transfer


“USA AMI” with transfer:

171 DB – 32 DN =

139 min delay


Prehospital Delay & Timing of Prehospital Delay & Timing of Reperfusion Strategy EquivalenceReperfusion Strategy Equivalence

Prehospital Delay & Timing of Prehospital Delay & Timing of Reperfusion Strategy EquivalenceReperfusion Strategy Equivalence

PC

I Rel

ated

Del

ay (

DB

-DN

) W

her

e P

CI R

elat

ed D

elay

(D

B-D

N)

Wh

ere

PC

I an

d F

ibri

no

lyti

c M

ort

alit

y A

re E

qu

al (

Min

)P

CI a

nd

Fib

rin

oly

tic

Mo

rtal

ity

Are

Eq

ual

(M

in)

0-120

121+NonAnt MI65+ YRS Ant MI 65+

YRS NonAnt MI<65 YRS Ant MI <65

YRS

179

168 148

107 103

58 43

400

60

120

180

Prehospital Prehospital Delay (min)Delay (min)

19,51719,517

5,2965,296

9,8129,812

41,77441,774

16,11916,119

20,42420,424

10,61410,614

3,7393,739


Gersh, B. J. et al. JAMA 2005;293:979-986.

Hypothetical Construct of the Relationship Among the Duration of Hypothetical Construct of the Relationship Among the Duration of Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction, Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction,

and Extent of Myocardial Salvageand Extent of Myocardial Salvage

Hypothetical Construct of the Relationship Among the Duration of Hypothetical Construct of the Relationship Among the Duration of Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction, Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction,

and Extent of Myocardial Salvageand Extent of Myocardial Salvage


One Size Does Not Fit All!One Size Does Not Fit All!


SummarySummarySummarySummary

Simple rules:Simple rules: DB<90 minDB<90 min DB-DN <60 minDB-DN <60 min DN <30 minDN <30 min Transfer all for PCI, etcTransfer all for PCI, etc

are not enough to determine the optimal are not enough to determine the optimal reperfusion strategy for all patients in all reperfusion strategy for all patients in all situationssituations



The clinician must integrate: The clinician must integrate: Prehospital DelayPrehospital Delay Anticipated STEMI Risk (age, anterior, inferior, Anticipated STEMI Risk (age, anterior, inferior,

shock)shock) Anticipated Risk for ICHAnticipated Risk for ICH Anticipated Transfer time/PCI related delayAnticipated Transfer time/PCI related delay



Fibrinolysis is not unreasonable whenFibrinolysis is not unreasonable when PCI associated with unacceptable delay (Class I)PCI associated with unacceptable delay (Class I) Short time from symptom onset (<1 hr) (Class I)Short time from symptom onset (<1 hr) (Class I)

Primary PCI is superior to Fibrinolysis in several Primary PCI is superior to Fibrinolysis in several clinical situations, particularly if:clinical situations, particularly if:

Competent personnel involvedCompetent personnel involved DB times are <90 Min, PCI related Delay AcceptableDB times are <90 Min, PCI related Delay Acceptable High Risk for Bleeding or Complication from MIHigh Risk for Bleeding or Complication from MI Late PresentationLate Presentation



The benefits and limitations of Primary PCI The benefits and limitations of Primary PCI should be considered when developing should be considered when developing regionalized transfer and community based regionalized transfer and community based PCI systemsPCI systems

Continued work is needed to develop Continued work is needed to develop pharmacologic strategies to rapidly, pharmacologic strategies to rapidly, effectively, and safely open closed arteries effectively, and safely open closed arteries thereby extending the benefit of PCI to a thereby extending the benefit of PCI to a larger group of patients larger group of patients

Question Question

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AnswerAnswer

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