Global Use of Strategies To Open Occluded Coronary Arteries IV-Acute Coronary Syndrome

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Global Use of Strategies To Open Occluded
Coronary Arteries IV-Acute Coronary Syndrome

• GUSTO IV-ACS

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GUSTO-IV ACS Objective

• To determine the effect of upstream
  administration of abciximab in patients with ACS
  who experience a delay to the cath lab.

GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO-IV ACS Study Design
7800 Patients with Non-ST-Elevation ACS (? 0.5 mm
ST ?, Troponin T or I)
Aspirin UF Heparin/Dalteparin No cath expected
for 48 hours
Abciximab x 48 hrs n 2612
Placebo n 2598
Abciximab x 24 hrs n 2590
Primary Endpoint Death or MI at 30 days after
randomization.
Superiority trial
GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO-IV ACS Inclusion Criteria

• ACS without persistent ST-segment elevation from
  one or more episodes of angina lasting at least 5
  min within the preceding 24 hours with
• Either
• Positive cTnT or cTnI test (above the ULN for the
  local qualitative or quantitative assay) or at
  least 05 mm of transient, or
• Persistent ST-segment depression not known to be
  preexisting and not attributable to coexisting
  disorders (eg, left-ventricular hypertrophy) or
  medication (eg, digoxin).
• Patients with a history of STEMI distinct from
  the presenting event within 10 days before
  enrolment were required to have new ST-segment
  depression and CKMB concentrations below the
  upper limits

GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO-IV ACS Endpoints

• Primary Death (from any cause) or MI within 30
  days after randomization.
• Secondary
• Death or MI within 30 days in patients with a
  cTnT greater than 01 g/L as measured by the
  central laboratory at baseline sample
• Death, MI, revascularisation, or cardiac
  catheterisation at 48 h, 7 days, and 30 days
• Death or MImwithin 30 days, and various
  combinations of these endpoints.

GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO-IV Drug Regimens
Regimen Study Drug Dose Heparin Dose ASA Dose
24 hour Abciximab Bolus 025 mg/kg followed by a 0125 µg/kg/min infusion up to a maximum of 10 µg/min for 24 hours UFH 70 U/kg bolus (to maximum of 5000 U) followed by infusion of 10 U/kg per h (to maximum of 800 U/h) titrated to aPTT between 50 and 70 s for 48 h after starting the study drug Dalteparin 120 IU/kg (to a maximum of 10 000 IU) subcutaneously every 12 h instead of UFH for 57 days or until a revascularization procedure or discharge 150325 mg orally or 250500 mg IV immediately after randomization, 75325 mg daily for at least 30 days
48 hour Abciximab Bolus 025 mg/kg followed by a 0125 µg/kg per min infusion up to a maximum of 10 µg/min for 48 hours UFH 70 U/kg bolus (to maximum of 5000 U) followed by infusion of 10 U/kg per h (to maximum of 800 U/h) titrated to aPTT between 50 and 70 s for 48 h after starting the study drug Dalteparin 120 IU/kg (to a maximum of 10 000 IU) subcutaneously every 12 h instead of UFH for 57 days or until a revascularization procedure or discharge 150325 mg orally or 250500 mg IV immediately after randomization, 75325 mg daily for at least 30 days
Placebo N/A UFH 70 U/kg bolus (to maximum of 5000 U) followed by infusion of 10 U/kg per h (to maximum of 800 U/h) titrated to aPTT between 50 and 70 s for 48 h after starting the study drug Dalteparin 120 IU/kg (to a maximum of 10 000 IU) subcutaneously every 12 h instead of UFH for 57 days or until a revascularization procedure or discharge 150325 mg orally or 250500 mg IV immediately after randomization, 75325 mg daily for at least 30 days
GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO-IV Patient Characteristics
Characteristic Placebo (n2598) 24-h Abciximab (n2590) 48-h Abciximab (n2612)
Age, years 65.2 65.1 65.3
Previous MI () 30 3 32
Diabetes () 22 21 22
ST depression () 80 81 80
Raised troponin () 31 34 32
Both ST depression and raised troponin () 31 34 32

• Age, is mean (SD).
• Cardiac troponin T or I above the upper limit
  of normal for local qualitative or quantitative
  assay.

GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO IV Death/MI at 30 Days
PNS
PNS
Patients
(Primary Endpoint)
GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO IV Safety
Plt.05
Plt.05
Patients
Plt.05
Plt.05
vs. placebo
GUSTO IV-ACS Investigators. Lancet.
20013571915-24
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GUSTO IV Mortality through 1 Year
PNS
Patients
PNS
PNS
P.008
Ottervanger JP et al. Circulation.
2003107437-442.
vs. placebo
GUSTO IV-ACS Investigators. Lancet.
20013571915-24