time is myocardium and the wavefront of necrosis cm gibson 2002

Time Is Myocardium and the Wavefront of NecrosisTime Is Myocardium and the Wavefront of NecrosisTime Is Myocardium and the Wavefront of NecrosisTime Is Myocardium and the Wavefront of Necrosis

CM Gibson 2002CM Gibson 2002

The DANAMI-2 TrialThe DANAMI-2 TrialThe DANAMI-2 TrialThe DANAMI-2 Trial

Danish Trial in Acute Myocardial Infarction-2

Presented at the American College of Cardiology 51st Annual Scientific Session

Atlanta, GA

Dr. Henning Rud Andersenfor the DANAMI-2 investigators

Danish Trial in Acute Myocardial Infarction-2

Presented at the American College of Cardiology 51st Annual Scientific Session

Atlanta, GA

Dr. Henning Rud Andersenfor the DANAMI-2 investigators

High-risk ST elevation MI patients (>4 mm elevation), Sx < 12 hrs5 PCI centers (n=443) and 22 referring hospitals (n=1,129), transfer in < 3 hrs

High-risk ST elevation MI patients (>4 mm elevation), Sx < 12 hrs5 PCI centers (n=443) and 22 referring hospitals (n=1,129), transfer in < 3 hrs

Lytic therapy

Front-loaded tPA 100 mg

(n=782)

Lytic therapy

Front-loaded tPA 100 mg

(n=782)

Death / MI / Stroke at 30 DaysDeath / MI / Stroke at 30 Days

DANAMI-2: Study DesignDANAMI-2: Study DesignDANAMI-2: Study DesignDANAMI-2: Study Design

Primary PCI

with transfer

(n=567)

Primary PCI

with transfer

(n=567)

Primary PCI

without transfer

(n=223)

Primary PCI

without transfer

(n=223)

Stopped early by safety and efficacy committeeStopped early by safety and efficacy committee

DANAMI-2: CentersDANAMI-2: CentersDANAMI-2: CentersDANAMI-2: Centers

14%

8%

0%

4%

8%

12%

16%14%

8%

0%

4%

8%

12%

16%

Dea

th /

MI /

Str

oke

(%

)D

eath

/ M

I / S

tro

ke (

%)

LyticLytic Primary PCIPrimary PCI

P=0.0003P=0.0003 P=0.002P=0.002

CombinedCombined Transfer SitesTransfer SitesP=0.048P=0.048

Non-Transfer SitesNon-Transfer Sites

DANAMI-2: Primary ResultsDANAMI-2: Primary ResultsDANAMI-2: Primary ResultsDANAMI-2: Primary Results

RRR 45%RRR 45%

LyticLytic Primary PCIPrimary PCI LyticLytic Primary PCIPrimary PCI

14%

9%

0%

4%

8%

12%

16%14%

9%

0%

4%

8%

12%

16%

12%

7%

0%

4%

8%

12%

16%

12%

7%

0%

4%

8%

12%

16%

RRR 40%RRR 40%

RRR 45%RRR 45%

9.6

13.7 14.1

16.1

0

2

46

8

1012

14

1618

30 days 6 months

PTCAt-PA

P=0.033 P=NS

GUSTO-IIb Angioplasty Substudy Investigators. N Engl J Med. 1997;336:1621-1628.

Trials Comparing Primary PTCA With Fibrinolytic Therapy: Trials Comparing Primary PTCA With Fibrinolytic Therapy: GUSTO-IIb Cohort GUSTO-IIb Cohort

Trials Comparing Primary PTCA With Fibrinolytic Therapy: Trials Comparing Primary PTCA With Fibrinolytic Therapy: GUSTO-IIb Cohort GUSTO-IIb Cohort

Co

mp

os

ite

Ou

tco

me

(%

)

2.0%

1.1%

0%

2%

4%

6%

8%

2.0%

1.1%

0%

2%

4%

6%

8%

6.3%

1.6%

0%

2%

4%

6%

8%

6.3%

1.6%

0%

2%

4%

6%

8%7.6%

6.6%

0%

2%

4%

6%

8% 7.6%

6.6%

0%

2%

4%

6%

8%


P=0.35P=0.35

DeathDeath

DANAMI-2: ResultsDANAMI-2: ResultsDANAMI-2: ResultsDANAMI-2: Results


P=0.15P=0.15

StrokeStroke


P<0.0001P<0.0001Recurrent MIRecurrent MI

DANAMI-2: Commentary on Low Rate of DANAMI-2: Commentary on Low Rate of Rescue/Adjunctive PCIRescue/Adjunctive PCI


• The benefit in the primary composite endpoint result is driven predominantly by a lower rate of recurrent MI among patients treated with fibrinolysis compared with primary PCI• Rescue PTCA for failed fibrinolysis was carried out

infrequently in DANAMI 2, in only 2.5% of cases.• The trial confirms what has been observed in the past:

fibrinolytic monotherapy when administered with unfractionated heparin is associated with a significant rate of recurrent myocardial infarction if not accompanied by either rescue, facilitated or delayed PCI.•It could be speculated that the incidence of recurrent MI may

be reduced with a more aggressive strategy of performing rescue or adjunctive PCI soon after fibrinolytic administration.

• The benefit in the primary composite endpoint result is driven predominantly by a lower rate of recurrent MI among patients treated with fibrinolysis compared with primary PCI• Rescue PTCA for failed fibrinolysis was carried out

infrequently in DANAMI 2, in only 2.5% of cases.• The trial confirms what has been observed in the past:

fibrinolytic monotherapy when administered with unfractionated heparin is associated with a significant rate of recurrent myocardial infarction if not accompanied by either rescue, facilitated or delayed PCI.•It could be speculated that the incidence of recurrent MI may

be reduced with a more aggressive strategy of performing rescue or adjunctive PCI soon after fibrinolytic administration.

Gibson CM, 2002Gibson CM, 2002

DANAMI-2: Commentary on Biases Inherent in the DANAMI-2: Commentary on Biases Inherent in the Assessment of the Recurrent MI EndpointAssessment of the Recurrent MI Endpoint

DANAMI-2: Commentary on Biases Inherent in the DANAMI-2: Commentary on Biases Inherent in the Assessment of the Recurrent MI EndpointAssessment of the Recurrent MI Endpoint

Among patients treated with fibrinolysis: Recurrent MI may be secondary to reocclusion of a patent infarct vessel following thrombolysis or may occur following delayed PCI after thrombolytic administration

Among patients treated with fibrinolysis: Recurrent MI may be secondary to reocclusion of a patent infarct vessel following thrombolysis or may occur following delayed PCI after thrombolytic administration


Among patients treated with primary PCI:

Recurrent MI may be secondary to stent thrombosis or late vessel occlusion several days following the procedure

Because of the inability to detect recurrent MI during the index primary PCI (unlike during the performance of a later delayed PCI), this limits the number of post PCI CK MIs detected in this strategy

Among patients treated with primary PCI:

Recurrent MI may be secondary to stent thrombosis or late vessel occlusion several days following the procedure

Because of the inability to detect recurrent MI during the index primary PCI (unlike during the performance of a later delayed PCI), this limits the number of post PCI CK MIs detected in this strategy



• Thus, the detection of post PCI CK elevations may be limited to only those patients enrolled in the fibrinolytic arm of the study• Determination of the timing of the recurrent MI is critical: did the recurrent MI occur before or after the PCI• Lower rates of GP 2b3a inhibitor use may be associated with higher rates of post PCI CK elevations, and it is critical to understand the proportion of patients treated with adjunctive GP 2b3a inhibition during elective or late PCI

• Thus, the detection of post PCI CK elevations may be limited to only those patients enrolled in the fibrinolytic arm of the study• Determination of the timing of the recurrent MI is critical: did the recurrent MI occur before or after the PCI• Lower rates of GP 2b3a inhibitor use may be associated with higher rates of post PCI CK elevations, and it is critical to understand the proportion of patients treated with adjunctive GP 2b3a inhibition during elective or late PCI


Thrombus Remains Following ThrombolysisThrombus Remains Following ThrombolysisThrombus Remains Following ThrombolysisThrombus Remains Following Thrombolysis

Van Belle et al. Van Belle et al. Circulation.Circulation. 1998;97:26-33. 1998;97:26-33.

Clinical Impact of Reocclusion: Clinical Impact of Reocclusion: Clinical Impact of Reocclusion: Clinical Impact of Reocclusion:

Data from the TAMI trials: Data from the TAMI trials:

• 810 patients, cath 90 min & 7 days later: 810 patients, cath 90 min & 7 days later:

• 12.4% reocclude12.4% reocclude

• 58% symptomatic58% symptomatic

• In-hospital mortality 11.0% vs 4.5% (In-hospital mortality 11.0% vs 4.5% (PP=0.01).=0.01).

Ohman et al. Ohman et al. Circulation.Circulation. 1990;82:781-791. 1990;82:781-791.

Recent Efforts to Reduce Reocclusion / ReinfarctionRecent Efforts to Reduce Reocclusion / ReinfarctionRecent Efforts to Reduce Reocclusion / ReinfarctionRecent Efforts to Reduce Reocclusion / Reinfarction

•In order to reduce the risk of reocclusion, several strategies have been employed in recent thrombolytic trials

– Mechanical• Adjunctive / Rescue / and delayed

PCI– Pharmacologic

• GP 2b3a inhibition• Treatment with the antithrombotic

agent enoxaparin

•In order to reduce the risk of reocclusion, several strategies have been employed in recent thrombolytic trials

– Mechanical• Adjunctive / Rescue / and delayed

PCI– Pharmacologic

• GP 2b3a inhibition• Treatment with the antithrombotic

agent enoxaparin


2 Year Survival Following Rescue PCI2 Year Survival Following Rescue PCI2 Year Survival Following Rescue PCI2 Year Survival Following Rescue PCI

Survival was Improved in patients with 90 minute TIMI Grade 0/1 Flow after TNK who underwent rescue PCI in the TIMI 10B trial

Survival was Improved in patients with 90 minute TIMI Grade 0/1 Flow after TNK who underwent rescue PCI in the TIMI 10B trial

CM Gibson, AHA 2001CM Gibson, AHA 2001

Su

rviv

al

Years

No PCI

Log rank p=0.006

Rescue PCI

0 .5 1 1.5 20.00

0.25

0.50

0.75

1.00

DANAMI 2: Commentary on Low Rate of DANAMI 2: Commentary on Low Rate of Rescue / Adjunctive PCI UseRescue / Adjunctive PCI Use

DANAMI 2: Commentary on Low Rate of DANAMI 2: Commentary on Low Rate of Rescue / Adjunctive PCI UseRescue / Adjunctive PCI Use

• In recent large scale thrombolytic trials in which rescue / adjunctive PCI has been performed more aggressively, lower rates of recurrent MI have been observed• In the setting of ST segment elevation MI treated with

thrombolytic monotherapy, the administration of enoxaparin has been associated with a reduced rate of reinfarction when compared to unfractionated heparin.• Would the use of Rescue / Adjunctive PCI and

enoxaparin have been associated with a lower rate of reinfarction in the DANAMI 2 study?

• In recent large scale thrombolytic trials in which rescue / adjunctive PCI has been performed more aggressively, lower rates of recurrent MI have been observed• In the setting of ST segment elevation MI treated with

thrombolytic monotherapy, the administration of enoxaparin has been associated with a reduced rate of reinfarction when compared to unfractionated heparin.• Would the use of Rescue / Adjunctive PCI and

enoxaparin have been associated with a lower rate of reinfarction in the DANAMI 2 study?


6.3%

4.2%

3.5%

2.3% 2.2%2.7%

1.8%

0%

1%

2%

3%

4%

5%

6%

7%

DANAMI ASSENT 3 GUSTO V GUSTO V ASSENT 3 ASSENT 3 ENTIRE

6.3%

4.2%

3.5%

2.3% 2.2%2.7%

1.8%

0%

1%

2%

3%

4%

5%

6%

7%

DANAMI ASSENT 3 GUSTO V GUSTO V ASSENT 3 ASSENT 3 ENTIRE

Rate of Rescue / Adjunctive PCI Use in DANAMI 2 Compared with Other Recent Rate of Rescue / Adjunctive PCI Use in DANAMI 2 Compared with Other Recent TrialsTrials

Rate of Rescue / Adjunctive PCI Use in DANAMI 2 Compared with Other Recent Rate of Rescue / Adjunctive PCI Use in DANAMI 2 Compared with Other Recent TrialsTrials

% R

ecur

rent

MI

% R

ecur

rent

MI

11.9%11.9%9.1%9.1%14.4%14.4%

17.4%17.4%19.4%19.4%16.5%16.5%

8.6%8.6% 5.6%5.6%

rPA + HeprPA + Hep rPA + AbxrPA + Abx TNK + EnoxTNK + EnoxTNK + AbxTNK + Abx

44.4%*44.4%*

TNK + HepTNK + Hep TNK + EnoxTNK + Enox

2.5%2.5%

tPA + HeptPA + Hep

Urgent PCIUrgent PCI

Non-Urgent

PCI

Non-Urgent

PCI

* Urgent & non-urgent combined* Urgent & non-urgent combinedCM Gibson 2002CM Gibson 2002

ENTIRE TIMI 23: 30 Day Death/MIENTIRE TIMI 23: 30 Day Death/MI ENTIRE TIMI 23: 30 Day Death/MIENTIRE TIMI 23: 30 Day Death/MI

2.5 2.6 3.7

12.2

3.9

3.7

1.81.9

0

5

10

15

20

UFH ENOX UFH ENOX

2.5 2.6 3.7

12.2

3.9

3.7

1.81.9

0

5

10

15

20

UFH ENOX UFH ENOXN = 82 160 77 164N = 82 160 77 164

% P

ts%

Pts

FULL Dose TNKFULL Dose TNK HALF Dose TNK + Abx

HALF Dose TNK + Abx

P=0.003P=0.003

DeathDeath

MIMI

15.915.9

4.44.46.56.5

5.55.5

P=0.005P=0.0053.1

8.2

3.1

1.8

0

4

8

12

UFH ENOX

3.1

8.2

3.1

1.8

0

4

8

12

UFH ENOX

11.311.3

4.94.9

P=0.01P=0.01

P=0.002P=0.002

159159 324324

ENTIRE TIMI 23: Recurrent MI In Patients NOT Undergoing PCI (N=259)

ENTIRE TIMI 23: Recurrent MI In Patients NOT Undergoing PCI (N=259)

9.8

1.9

5.3

0.00

2

4

6

8

10

UFH ENOX UFH ENOX

9.8

1.9

5.3

0.00

2

4

6

8

10

UFH ENOX UFH ENOX

% P

ts%

Pts

4141

FULL Dose TNKFULL Dose TNK HALF Dose TNK + Abx

HALF Dose TNK + Abx

103103 3838 7777N=N=

7.6

1.10

2

4

6

8

10

UFH ENOX

7.6

1.10

2

4

6

8

10

UFH ENOX

7979 180180

DANAMI-2 Commentary on Door to Balloon TimesDANAMI-2 Commentary on Door to Balloon TimesDANAMI-2 Commentary on Door to Balloon TimesDANAMI-2 Commentary on Door to Balloon Times

•In DANAMI 2, door-to-balloon times were approximately 114 minutes for those patients transferred to another facility

•Based upon the data presented by Cannon et al, a door-to-balloon time of 114 minutes was not associated with a significant increase in mortality in the NRMI 2 database when compared to a door-to-balloon time of < one hour

•If transfer for primary PCI is elected, then door to balloon times should be similar to those observed in DANAMI 2

•In NRMI 4, the current median door to balloon time among patients transferred to another facility in the US for primary PCI is much longer at 198 minutes

•In DANAMI 2, door-to-balloon times were approximately 114 minutes for those patients transferred to another facility

•Based upon the data presented by Cannon et al, a door-to-balloon time of 114 minutes was not associated with a significant increase in mortality in the NRMI 2 database when compared to a door-to-balloon time of < one hour

•If transfer for primary PCI is elected, then door to balloon times should be similar to those observed in DANAMI 2

•In NRMI 4, the current median door to balloon time among patients transferred to another facility in the US for primary PCI is much longer at 198 minutes


Community HospitalThrombolysis

(n=782)

Community HospitalThrombolysis

(n=782)

PCI, non-transportedpatients(n=223)

PCI, non-transportedpatients(n=223)

PCI, transportedpatients(n=567)

PCI, transportedpatients(n=567)

DANAMI 2: Door to Balloon TimesDANAMI 2: Door to Balloon TimesDANAMI 2: Door to Balloon TimesDANAMI 2: Door to Balloon Times

11.14 1.15

1.41

1.62 1.61

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0-6

0

61

-90

91

-12

0

12

1-1

50

15

1-1

80

>1

80

MV

Ad

jus

ted

Od

ds

of

De

ath

Cannon CP et al, JAMA 2000Cannon CP et al, JAMA 2000

4.2 4.6 5.1

6.7

8.57.9

0

2

4

6

8

10

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

Mo

rta

lity

(%

)

4.2 4.6 5.1

6.7

8.57.9

0

2

4

6

8

10

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

Mo

rta

lity

(%

)

N=27,080P < 0.00001

N=27,080P < 0.00001

NRMI-2: Primary PCI Door-to-Balloon time vs. MortalityNRMI-2: Primary PCI Door-to-Balloon time vs. Mortality

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

Door to Balloon Times Among Patients Transferred in NRMI 4Door to Balloon Times Among Patients Transferred in NRMI 4Door to Balloon Times Among Patients Transferred in NRMI 4Door to Balloon Times Among Patients Transferred in NRMI 4

NRMI 4 Transfer-In Annual Data Report 2002NRMI 4 Transfer-In Annual Data Report 2002

Door to

Data:

50th: 8 Min.

25th: 4 Min.

75th: 16 Min.

Door to

Data:

50th: 8 Min.

25th: 4 Min.

75th: 16 Min.

Data to

Cath Lab Arrival:

50th: 137 Min.

25th: 87 Min.

75th: 220 Min.

Data to

Cath Lab Arrival:

50th: 137 Min.

25th: 87 Min.

75th: 220 Min.

Cath Lab to

Balloon:

50th: 39 Min.

25th: 29 Min

75th: 53 Min.

Cath Lab to

Balloon:

50th: 39 Min.

25th: 29 Min

75th: 53 Min.

88 137137 3939

Total Door to Balloon Time: 198 minutes (25th: 137; 75th: 281)

Percent of Patients with Door to Balloon Time < 90 Min.: 4.8%

Total Door to Balloon Time: 198 minutes (25th: 137; 75th: 281)

Percent of Patients with Door to Balloon Time < 90 Min.: 4.8%

Sample Size: 1,292; Time Period: October 2000 – September 2001Sample Size: 1,292; Time Period: October 2000 – September 2001


Importance of Operator Experience and Volume in Primary PCI Importance of Operator Experience and Volume in Primary PCI OutcomesOutcomes

Importance of Operator Experience and Volume in Primary PCI Importance of Operator Experience and Volume in Primary PCI OutcomesOutcomes

•A significant proportion of the DANAMI operators had little prior experience with primary PCI.

•Is operator and hospital volume associated with PCI outcomes in larger series?

•A significant proportion of the DANAMI operators had little prior experience with primary PCI.

•Is operator and hospital volume associated with PCI outcomes in larger series?


NRMI 2-3: Primary PCI vs. Thrombolysis: 1996-2000NRMI 2-3: Primary PCI vs. Thrombolysis: 1996-2000N=62,000 PatientsN=62,000 Patients

NRMI 2-3: Primary PCI vs. Thrombolysis: 1996-2000NRMI 2-3: Primary PCI vs. Thrombolysis: 1996-2000N=62,000 PatientsN=62,000 Patients

Volume % Hosp TlysisPrim PCI P value

< 16 /yr 25% 5.9 6.2 NS17-48/yr 50% 5.9 4.5 <0.001>48/yr 25% 5.4 3.4 <0.001

Non-fatal stroke 1.1 0.4 <0.001

Volume % Hosp TlysisPrim PCI P value

< 16 /yr 25% 5.9 6.2 NS17-48/yr 50% 5.9 4.5 <0.001>48/yr 25% 5.4 3.4 <0.001

Non-fatal stroke 1.1 0.4 <0.001

In-hospital Mortality

Magid et al. JAMA 2000

8.0

6.2

4.7

0

2

4

6

8

10

<1 1-3 >3

Mo

rtal

ity

(%)

8.0

6.2

4.7

0

2

4

6

8

10

<1 1-3 >3

Mo

rtal

ity

(%)

N=27,080P < 0.00001

N=27,080P < 0.00001

NRMI-2: Primary PCI Institutional Volume vs. Mortality

NRMI-2: Primary PCI Institutional Volume vs. Mortality

Institutional Monthly Volume of Primary Angioplasty CasesInstitutional Monthly Volume of Primary Angioplasty Cases

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

4.8

7.9

6.2

8.3

10.410.0

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

4.8

7.9

6.2

8.3

10.410.0

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

4.3 4.2

5.6

6.9

8.0 8.1

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

4.3 4.2

5.6

6.9

8.0 8.1

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

3.7 3.63.9

5.6

8.0

5.8

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

3.7 3.63.9

5.6

8.0

5.8

0

2

4

6

8

10

12

0-60 61-90

91-120

121-150

151-180

>180

Mo

rta

lity

(%

<1 / monthN=4,740

P = 0.0008

<1 / monthN=4,740

P = 0.0008

1-3 / monthN=14,078P < 0.0001

1-3 / monthN=14,078P < 0.0001

>3 / monthN=14,078P < 0.0001

>3 / monthN=14,078P < 0.0001

Primary PCI: Door-to-Balloon time vs. Mortality Stratified by Institutional Volume

Primary PCI: Door-to-Balloon time vs. Mortality Stratified by Institutional Volume

Hospital Volume of Primary PTCA vs. MortalityHospital Volume of Primary PTCA vs. Mortality

0.870.72

0.83

P value for trend < 0.001

Canto. NEJM 2000Canto. NEJM 2000

N: Pt = 2,825 5,245 9,303 19,162 Hosp =113 112 113 112

0

0.2

0.4

0.6

0.8

1

1.2

5 to 11 12 to 20 21 to 33 >33Hospital Volume of Primary Angioplasty per Year

MV

Ad

just

ed O

dd

s o

f D

eath

0

0.2

0.4

0.6

0.8

1

1.2

5 to 11 12 to 20 21 to 33 >33Hospital Volume of Primary Angioplasty per Year

MV

Ad

just

ed O

dd

s o

f D

eath

Randomized Trial Results Versus Community-Setting Results: Randomized Trial Results Versus Community-Setting Results: NRMI-2 CohortNRMI-2 Cohort

Randomized Trial Results Versus Community-Setting Results: Randomized Trial Results Versus Community-Setting Results: NRMI-2 CohortNRMI-2 Cohort

Tiefenbrunn AJ, et al. J Am Coll Cardiol. 1998;31:1240-1245.

5.2 5.4 5.66.2

0

2

4

6

8

In-hospital mortality In-hospital mortality ornonfatal stroke

PTCA t-PA

PP=NS=NS

PP=NS=NS

Pe

rce

nt

n=2,958, lytic eligible, no shock at presentation n=2,958, lytic eligible, no shock at presentation

70

75

80

85

90

95

100

0 0.5 1 1.5 2 2.5 3 3.5 4

Su

rviv

al (

%)

Time After Discharge (years)Time After Discharge (years)

Every NR, et al. N Engl J Med. 1996;335:1253-1260.

P=0.80

Trials Comparing Primary PTCA With Fibrinolytic Therapy: MITI Trials Comparing Primary PTCA With Fibrinolytic Therapy: MITI CohortCohort

Trials Comparing Primary PTCA With Fibrinolytic Therapy: MITI Trials Comparing Primary PTCA With Fibrinolytic Therapy: MITI CohortCohort

Thrombolytic therapy

Primary angioplasty

DANAMI-2 Commentary: Facilitated PCI Not DANAMI-2 Commentary: Facilitated PCI Not EvaluatedEvaluated

DANAMI-2 Commentary: Facilitated PCI Not DANAMI-2 Commentary: Facilitated PCI Not EvaluatedEvaluated

•This trial tested the efficacy of thrombolytic therapy with very little use of rescue/adjunctive PCI (2.5%) versus “primary PCI” without significant pharmacologic therapy before the PCI

•The trial provides no data regarding the efficacy of “facilitated PCI” in which a thrombolytic agent or GP 2b3a inhibitor would be administered prior to rescue or adjunctive PCI.

• The concept of “facilitated PCI” will be tested in upcoming trials.

•This trial tested the efficacy of thrombolytic therapy with very little use of rescue/adjunctive PCI (2.5%) versus “primary PCI” without significant pharmacologic therapy before the PCI

•The trial provides no data regarding the efficacy of “facilitated PCI” in which a thrombolytic agent or GP 2b3a inhibitor would be administered prior to rescue or adjunctive PCI.

• The concept of “facilitated PCI” will be tested in upcoming trials.


0

20

40

60

80

100

0 30 45 60 75 90 120 150

Time (minutes)Time (minutes)

Relative Speed and Magnitude of PatencyRelative Speed and Magnitude of PatencyRelative Speed and Magnitude of PatencyRelative Speed and Magnitude of Patency

ED

arrival

ED

arrival

Drug

administration

Drug

administration

Adapted from Gibson CM. Am Interm Med. 1999;130:841-847.Adapted from Gibson CM. Am Interm Med. 1999;130:841-847.

Lytic + 2b3a:

94% by 60 min.

LyticLytic

2 hour

Door to

Balloon

2 hour

Door to

Balloon

Pre Hospital Drug

administration

Pre Hospital Drug

administration

Pre Hospital Lytic+ 2b3a

Pre Hospital Lytic+ 2b3a

PlaceboPlacebo tPAtPA

Adapted from Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.Adapted from Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

PACTPACT

% T

IMI

2/3

flo

w p

re P

CI

% T

IMI

2/3

flo

w p

re P

CI

15 17

12

30

0

10

20

30

40

50

TIMI 3

TIMI 2

PRAGUE*PRAGUE*

PlaceboPlacebo SKSK

% T

IMI

2/3

flo

w p

re P

CI

% T

IMI

2/3

flo

w p

re P

CI

Fibrinolytic Therapy Pre-PCIFibrinolytic Therapy Pre-PCI

* Patients transferred for PCI

Adapted from Widimsky P, et al. J Eur Heart J. 2000;21:823-831.Adapted from Widimsky P, et al. J Eur Heart J. 2000;21:823-831.

1533

19

28

0

10

20

30

40

50

60

70

TIMI 3

TIMI 2

62.457.9

54.7

0

20

40

60

80

TIMI 3 on cath lab arrival TIMI 3 after leaving cath lab Never had TIMI 3

Adapted from Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.Adapted from Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

% C

on

va

les

cen

t L

VE

F

Convalescent LV Function by Patency Group: Global Ejection Convalescent LV Function by Patency Group: Global Ejection FractionFraction

Convalescent LV Function by Patency Group: Global Ejection Convalescent LV Function by Patency Group: Global Ejection FractionFraction

P=0.004

Relationship of TIMI 3 Flow Before PCI to 6 Month Relationship of TIMI 3 Flow Before PCI to 6 Month SurvivalSurvival

Relationship of TIMI 3 Flow Before PCI to 6 Month Relationship of TIMI 3 Flow Before PCI to 6 Month SurvivalSurvival

Stone et al. Circ 2001; 104: 636-641Stone et al. Circ 2001; 104: 636-641

Preliminary Designs of Upcoming Facilitated PCI TrialsPreliminary Designs of Upcoming Facilitated PCI Trials

ASSENT 4ASSENT 4 TNKTNK Heparin / ASAHeparin / ASA

ADVANCEADVANCE TNK + IntegrilinTNK + Integrilin IntegrilinIntegrilin

TIGERTIGER TNKTNK TNK + IntegrilinTNK + Integrilin

TITANTITAN Integrilin in ERIntegrilin in ER Integrilin in Cath Integrilin in Cath LabLab

FINESSEFINESSE rPArPA rPA + abciximab in rPA + abciximab in ER vs CCLER vs CCL


DANAMI 2 ConclusionsDANAMI 2 ConclusionsDANAMI 2 ConclusionsDANAMI 2 Conclusions

• Among patients transferred for primary PCI with a median door to balloon time of 114 minutes, the incidence of the composite endpoint of death, recurrent MI, and stroke is reduced compared with the administration of tPA and heparin when used in conjunction with a rescue / adjunctive PCI rate of 2.5%.

• Among patients transferred for primary PCI with a median door to balloon time of 114 minutes, the incidence of the composite endpoint of death, recurrent MI, and stroke is reduced compared with the administration of tPA and heparin when used in conjunction with a rescue / adjunctive PCI rate of 2.5%.



• The median US door to balloon time for transfer patients is 198 minutes, and is not as rapid as in DANAMI 2 (114 minutes)

• The composite endpoint was driven primarily by a lower rate of recurrent MI among PCI patients

• Current strategies that employ higher rates of rescue and adjunctive PCI after fibrinolysis and higher rates of enoxaparin use have been associated with lower rates of recurrent MI than that reported in DANAMI 2

• The median US door to balloon time for transfer patients is 198 minutes, and is not as rapid as in DANAMI 2 (114 minutes)

• The composite endpoint was driven primarily by a lower rate of recurrent MI among PCI patients

• Current strategies that employ higher rates of rescue and adjunctive PCI after fibrinolysis and higher rates of enoxaparin use have been associated with lower rates of recurrent MI than that reported in DANAMI 2



• As an endpoint, recurrent MI may more often be detected among patients treated with fibrinolysis who undergo delayed or late PCI because post PCI CK release may not be detected during primary PCI

• DANAMI 2 trial was performed in a dedicated network of centers. Larger hospital / and operator volumes are associated with improved outcomes and the ability to implement this strategy in smaller volume hospital systems with less experienced operators is not yet tested

• To this end, US community hospital registry experience suggests no benefit of primary PCI over fibrinolysis

• As an endpoint, recurrent MI may more often be detected among patients treated with fibrinolysis who undergo delayed or late PCI because post PCI CK release may not be detected during primary PCI

• DANAMI 2 trial was performed in a dedicated network of centers. Larger hospital / and operator volumes are associated with improved outcomes and the ability to implement this strategy in smaller volume hospital systems with less experienced operators is not yet tested

• To this end, US community hospital registry experience suggests no benefit of primary PCI over fibrinolysis



• DANAMI 2 did not assess the effectiveness of “facilitated PCI” in which pharmacologic and mechanical strategies are combined.

• Upcoming trials will test the effectiveness of “facilitated PCI”

• DANAMI 2 did not assess the effectiveness of “facilitated PCI” in which pharmacologic and mechanical strategies are combined.

• Upcoming trials will test the effectiveness of “facilitated PCI”


time is myocardium and the wavefront of necrosis cm gibson 2002

Documents

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study design primary

hospitals n

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death danami

combined transfer sites