GUSTO IV ACS: Trial DesignGUSTO IV ACS: Trial Design

•Abciximab versus placebo in very high-risk patients with non-ST elevation acute coronary syndromes:

– ST> 0.5 mm or– elevated troponin I– Medical management for at least 60 hours– If a patient underwent PCI within 30 days,

abciximab permitted in all patients

•Primary Endpoint: 30 day death / MI

Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

GUSTO IV ACS Trial: TherapiesGUSTO IV ACS Trial: Therapies

•Randomized to receive either:– Placebo for 48 hours– Abciximab 0.25 mg/kg bolus plus 0.125 g/kg/min for 24

hours followed by placebo for 24 hours– Abciximab 0.25 mg/kg bolus plus 0.125 g/kg/min for 48

hours. •All patients received aspirin and heparin•Over 900 patients received dalteparin instead of

heparin in a substudy.•PCI was not allowed until 60 hours post-

randomization.•CABG surgery to be delayed until 72 hours post-

randomization. Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

GUSTO IV: Baseline DemographicsGUSTO IV: Baseline Demographics

GUSTO IV PURSUIT

Females 38% 36%

Diabetics 22% 23%

Prior MI 30% 32%

Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

GUSTO IV: 30 Day OutcomesGUSTO IV: 30 Day Outcomes

8.0

3.9

8.2

3.4

9.1

4.2

0

2

4

6

8

10

Death/MI Death

%

Placebo

Abciximab 24 hours

Abciximab 48 hours

• 1.1% higher risk of death / MI among patients treated with 48 hour infusion of abciximab did not reach statistical significance

P = NS for all

Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

0.3

1.5

0.7

0.08

0.60.8

0.19

1.0

3.6

1.3

0.15

2.5

0

1

2

3

4

Major bleeding Minor bleeding Transfusion Intracranialhemorrhage

%

PlaceboAbciximab 24 hoursAbciximab 48 hours

*

*

**

GUSTO IV: Bleeding RiskGUSTO IV: Bleeding Risk

* P < 0.05

Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

8.0

5.3

8.2

5.9

9.1

6.0

0

2

4

6

8

10

TroponinPositive

TroponinNegative

%

Placebo

Abciximab 24 hours

Abciximab 48 hours

• Troponin-positive patients were a subgroup with particular benefit in previous 2b/3a trials

• They represent a higher-risk group

• Troponin results were obtained from bedside assays

• No benefit observed among these high risk patients

GUSTO IV ACS Trial: Results in Troponin + PatientsGUSTO IV ACS Trial: Results in Troponin + Patients

Preliminary Results of GUSTO IV presented at European Society of Cardiology August 2000

GUSTO IV ACS Trial: Discussion of Negative Trial ResultsGUSTO IV ACS Trial: Discussion of Negative Trial Results

•Fewer interventions than in previous trials of GP 2b/3a inhibitors

– Fewer than 5% of patients underwent PCI during intervention

•The maintenance dose of abciximab may have been insufficient