Assessment of the Safety and Efficacy of a New Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction Treatment Strategy for Acute Myocardial Infarction

(ASSENT-4 PCI) Trial(ASSENT-4 PCI) Trial

Assessment of the Safety and Efficacy of a New Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction Treatment Strategy for Acute Myocardial Infarction

(ASSENT-4 PCI) Trial(ASSENT-4 PCI) Trial

ASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI Trial

Presented atPresented atThe European Society of CardiologyThe European Society of Cardiology

Hot Line Session 2005Hot Line Session 2005

Presented by Dr. Frans Van de WerfPresented by Dr. Frans Van de Werf

www. Clinical trial results.org

Full-dose TNK + Primary PCIn=829

GP IIb/IIIa inhibitors allowed only for bail out use

Full-dose TNK + Primary PCIn=829

GP IIb/IIIa inhibitors allowed only for bail out use

ASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI Trial

1667 patients with ST elevation myocardial infarction (summed ST deviation > 6 mm); time from symptom onset within 6 hrs; intent to perform primary PCI

RandomizedMean follow-up: 6 mos (30 days reported to date)

63% of patients received clopidogrel/ticlopidine during PCI Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group

1667 patients with ST elevation myocardial infarction (summed ST deviation > 6 mm); time from symptom onset within 6 hrs; intent to perform primary PCI

RandomizedMean follow-up: 6 mos (30 days reported to date)

63% of patients received clopidogrel/ticlopidine during PCI Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group

Presented at ESC 2005Presented at ESC 2005

Primary PCIn=838

GP IIb/IIIa inhibitors allowed at discretion of physician

Primary PCIn=838

GP IIb/IIIa inhibitors allowed at discretion of physician

Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days.

Secondary Endpoint: Composite of death, shock, or congestive heart failure at 30 days; shock or CHF at 90 days; single components of the composite endpoint.

Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days.

Secondary Endpoint: Composite of death, shock, or congestive heart failure at 30 days; shock or CHF at 90 days; single components of the composite endpoint.

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ASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI TrialASSENT- 4 PCI Trial

87.1% 91.1%

0%

20%

40%

60%

80%

100%

TNK + PCI PCI alone

87.1% 91.1%

0%

20%

40%

60%

80%

100%

TNK + PCI PCI alone

Patients undergoing PCIamong two treatment groups (%)

p=0.01

0.2%

9.6%3.0%

50.5%

0%

20%

40%

60%

GP IIb/IIIa inhibitorsprior to PCI

GP IIb/IIIa inhibitorsduring PCI

TNK + PCI PCI alone

0.2%

9.6%3.0%

50.5%

0%

20%

40%

60%

GP IIb/IIIa inhibitorsprior to PCI

GP IIb/IIIa inhibitorsduring PCI

TNK + PCI PCI alone

GP IIb/IIIa inhibitor administration prior to and during PCI (%)

p<0.001

Presented at ESC 2005Presented at ESC 2005

• PCI was performed at a median of 104 minutes following TNK bolus administration• Median time from symptom onset to randomization was 140 minutes in the combined therapy group and 135 minutes in the PCI alone group• 19% of patients were randomized in the ambulance

www. Clinical trial results.org Presented at ESC 2005Presented at ESC 2005

ASSENT- 4 PCI Trial: TIMI Flow GradeASSENT- 4 PCI Trial: TIMI Flow GradeASSENT- 4 PCI Trial: TIMI Flow GradeASSENT- 4 PCI Trial: TIMI Flow Grade

43.6%

95.3%

15.0%

97.6%

0%

20%

40%

60%

80%

100%

TFG 3 prior to PCI TFG 2/3 post-PCI

TNK + PCI PCI alone

43.6%

95.3%

15.0%

97.6%

0%

20%

40%

60%

80%

100%

TFG 3 prior to PCI TFG 2/3 post-PCI

TNK + PCI PCI alone

TIMI grade 3 flow prior to PCI and TIMI grade 2/3 flow post-PCI (%)

p<0.001p<0.001

•TIMI grade 3 flow prior to PCI was present more frequently in the TNK + PCI arm (43.6% vs 15.0%)

•TIMI grade 2/3 post-PCI was slightly higher in the PCI alone group (95.3% vs 97.6%)

www. Clinical trial results.org Presented at ESC 2005Presented at ESC 2005

ASSENT- 4 PCI Trial: Abrupt Closure ASSENT- 4 PCI Trial: Abrupt Closure and Re-infarctionand Re-infarction

ASSENT- 4 PCI Trial: Abrupt Closure ASSENT- 4 PCI Trial: Abrupt Closure and Re-infarctionand Re-infarction

1.9%

4.1%

0.1%

1.9%

0%

2%

4%

Abrupt closure Re-infarction

TNK + PCI PCI alone

1.9%

4.1%

0.1%

1.9%

0%

2%

4%

Abrupt closure Re-infarction

TNK + PCI PCI alone

Analysis of in-hospital abrupt closure and re-infarction among two treatment groups (%)

p<0.001p<0.001

• In-hospital abrupt closure occurred more often in the TNK + PCI treatment group (1.9% vs 0.1%)

• Re-infarction occurred more often in the TNK + PCI treatment group (4.1% vs 1.9%)

p=0.01p=0.01

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ASSENT- 4 PCI Trial: Mortality at 30 daysASSENT- 4 PCI Trial: Mortality at 30 daysASSENT- 4 PCI Trial: Mortality at 30 daysASSENT- 4 PCI Trial: Mortality at 30 days

6.0%

3.8%

0%

2%

4%

6%

8%

TNK + PCI PCI alone

6.0%

3.8%

0%

2%

4%

6%

8%

TNK + PCI PCI alone

•The primary endpoint of mortality was higher in the TNK + PCI treatment group compared with the PCI alone group (6.0% vs 3.8%, p=0.04) at 30 days

Analysis of mortality at 30 days (%)p = 0.04

Presented at ESC 2005Presented at ESC 2005

n=50 n=32

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ASSENT- 4 PCI Trial: Stroke and ICH at 30 daysASSENT- 4 PCI Trial: Stroke and ICH at 30 daysASSENT- 4 PCI Trial: Stroke and ICH at 30 daysASSENT- 4 PCI Trial: Stroke and ICH at 30 days

•Total stroke occurred more often in the TNK + PCI group (1.8% vs 0%), as did ICH (0.97% vs 0%) at 30 days

Analysis of total Stroke and ICH at 30 days (%)

Presented at ESC 2005Presented at ESC 2005

1.80%

0.97%

0 00.0%

0.5%

1.0%

1.5%

2.0%

Stroke ICH

TNK + PCI PCI alone

1.80%

0.97%

0 00.0%

0.5%

1.0%

1.5%

2.0%

Stroke ICH

TNK + PCI PCI alone

p<0.001p<0.001

p=0.004p=0.004

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ASSENT- 4 PCI Trial: Bleeding Events at 30 daysASSENT- 4 PCI Trial: Bleeding Events at 30 daysASSENT- 4 PCI Trial: Bleeding Events at 30 daysASSENT- 4 PCI Trial: Bleeding Events at 30 days

• No difference in the frequency of major bleed existed between the two treatment groups (5.7% vs 4.4%) at 30 days

•The presence of any bleeding event was more common in the TNK+ PCI treatment group (31.3% vs 23.4%) at 30 days

Analysis of bleeding events at 30 days (%)

Presented at ESC 2005Presented at ESC 2005

5.7%

31.3%

4.4%

23.4%

0%

10%

20%

30%

Major bleed Any bleeding event

TNK + PCI PCI alone

5.7%

31.3%

4.4%

23.4%

0%

10%

20%

30%

Major bleed Any bleeding event

TNK + PCI PCI alone

p=0.26p=0.26

p<0.001p<0.001

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ASSENT- 4 PCI Trial: SummaryASSENT- 4 PCI Trial: SummaryASSENT- 4 PCI Trial: SummaryASSENT- 4 PCI Trial: Summary

•The trial intended to enroll 4,000 patients, but was discontinued early after enrollment of 1,667 patients.

•Among patients with ST elevation MI intended for primary PCI, administration of full-dose fibrinolytic (TNK) immediately prior to PCI was associated with increased mortality and stroke at 30 days compared with primary PCI alone.

•Primary endpoint data are not yet available.

•Further evaluation of the clinical benefit of fibrinolytics among patients undergoing early PCI for STEMI appears warranted (FINESSE).

•The trial intended to enroll 4,000 patients, but was discontinued early after enrollment of 1,667 patients.

•Among patients with ST elevation MI intended for primary PCI, administration of full-dose fibrinolytic (TNK) immediately prior to PCI was associated with increased mortality and stroke at 30 days compared with primary PCI alone.

•Primary endpoint data are not yet available.

•Further evaluation of the clinical benefit of fibrinolytics among patients undergoing early PCI for STEMI appears warranted (FINESSE).

Presented at ESC 2005Presented at ESC 2005