Global Use of Strategies To Open Occluded Coronary Arteries IV-Acute Coronary Syndrome - GUSTO IV-ACS One Year Follow-up

Description:

The goal of this trial was to evaluate the efficacy of Abciximab in NSTEMI/UA patients not planned to undergo PCI

Hypothesis:

IV administration of the GP IIb/IIIa inhibitor abciximab will reduce the composite endpoint of death or MI in patients with high-risk acute coronary syndromes not undergoing early revascularization.

Study Design

Study Design:

Patients Enrolled: 7,800
Mean Follow Up: 1 year
Mean Patient Age: mean age 65
Female: 37%

Patient Populations:

Age >=21 years; >=1 episodes of angina lasting >5 minutes within 24 hours before admission; either an abnormal cardiac troponin T or I test or >=0.5 mm of transient or persistent ST-segment depression

Exclusions:

Myocardial ischemia precipitated by a disorder other than atherosclerotic coronary artery disease, persistent ST-segment-elevation MI, or new LBBB; PCI within previous 14 days; planned PCI or CABG within 30 days after enrollment; active internal bleeding or history of hemorrhagic diathesis; major surgery, serious trauma or gastrointestinal or genitourinary bleeding of clinical significance within the previous 6 weeks; intracranial neoplasm or aneurysm, atrioventricular malformation, history of stroke within 2 years, or prior stroke with a residual neurological deficit; oral anticoagulation within the previous 7 days unless the INR was <=1.4; platelet count <100,000/uL; confirmed hypertension (SBP>180 or DBP mm Hg); history of vasculitis; puncture of non-compressible vessel within 24 h before enrollment; allergy to abciximab or other murine proteins; weight >120 kg; a coexisting disorder associated with limited life expectancy; and participation in another investigational trial within 7 days

Primary Endpoints:

All-cause mortality or MI by day 30

Secondary Endpoints:

1) death or MI within 30 days in patients with a troponin T >0.1 ug/L 2) death, MI, revascularization, or cardiac catheterization at 48 h, 7 days, and 30 days 3) death by 1 year

Drug/Procedures Used:

Patients were randomized to one of the following: 1) Abciximab therapy for 24 h (0.25 mg/kg bolus followed by a 0.125 ug/kg/min infusion up to a maximum of 10 ug/min for 24 h) followed by 24 h placebo infusion; 2) Abciximab therapy for 48 h (same bolus and infusion for total duration of 48 h); 3) Matching placebo (bolus and 48 h infusion).

Concomitant Medications:

ASA 150–325 mg as soon as possible after randomization, plus 75–325 mg daily for at least 30 days. 70 U/kg UFH bolus (maximum of 5000 U) plus continuous infusion of 10 U/kg/h (maximum of 800 U/h) titrated to maintain the APTT 50-70s for 48 h after starting the study drug.

Principal Findings:

Coronary revascularization was performed in 30% of patients by 30 days with no difference by treatment arm. Only 2% of patients underwent revascularisation within 48 hours while on study therapy. There was no significant difference in the primary endpoint of death or MI at 30 days by treatment group (8.0% placebo arm vs 8.2% 24-hour abciximab arm [odds ratio 1.0, p=NS] vs 9.1% in 48-hour arm [OR=1.1, p=NS]). Likewise, the composite of death/MI did not differ at 48 hours (1.5% vs 1.9% vs 2.2%, p=0.07) or 7 days (4.5% vs 4.0% vs 4.1%, p=0.426). The individual components of the composite did not differ at any timepoint with the exception of mortality at 48 hours (0.3% vs 0.7% vs 0.9%, p=0.008). No difference in mortality occurred by 1 year (7.8% placebo arm vs 8.2% 24-hour arm [hazard ratio 1.1, p=NS] vs 9.0% 48-hour arm [HR=1.2, p=NS]). There was no benefit associated with abciximab therapy at 30 days or 1 year observed in any of the subgroups studied.

Interpretation:

Among patients with NSTEMI/UA not planned for early revascularization, treatment with abciximab was not associated with a benefit in death or MI at 30 days, in fact there was a mortality hazard. Likewise, no mortality benefit with abciximab was observed at 1 year. Based on these findings, use of the GP IIb/IIIa inhibitor abciximab in NSTEMI/UA patients without planned PCI is contraindicated in the current AHA/ACC guidelines. However, use of a GP IIb/IIIa inhibitor with planned PCI has been shown to be beneficial in many trials and is recomended therapy in the AHA/ACC guidelines.

References:

Primary results: Lancet 2001; 357: 1915–1924. 1 year follow-up: Circulation 2003;107:437-442.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Troponin T, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Platelet Glycoprotein GPIIb-IIIa Complex


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