Acute Catheterization and Urgent Intervention Triage Strategy Trial - ACUITY

Description:

The goal of the trial was to evaluate treatment with heparin plus glycoprotein (GP) IIb/IIIa inhibition compared with bivalirudin with or without GP IIb/IIIa inhibition among patients with acute coronary syndromes.

Hypothesis:

1) Bivalirudin with routine GPIIb/IIIa inhibition will be non-inferior to heparin with routine GPIIb/IIIa inhibition and 2) Bivalirudin reduces major bleeding compared with heparin with routine GPIIb/IIIa inhibition while being not inferior for ischemic complications.

Study Design

  • Randomized

Patients Enrolled: 13819
Mean Follow Up: One year (30 days reported to date)
Mean Patient Age: Median age 63 years
Female: 30

Patient Populations:

Unstable angina or non ST-segment elevation MI with 10 minutes of cardiac chest pain within 24 hours, plus one of the following: troponin or CK-MB elevation, dynamic EKG changes, documented prior coronary artery disease, or all of the following four features: 1) age ≥65 years; 2) aspirin taken in prior 7 days; 3) ≥2 episodes of angina in the prior 24 hours; 4) ≥3 of the following risk factors: hypertension, hypercholesterolemia, family history or coronary artery disease, diabetes, current smoker.

Exclusions:

Anticipated inability to perform angiography within 72 hours of randomization, or indicated revascularization within the index hospitalization; acute ST elevation MI; cardiogenic shock; bleeding diathesis or history of intracerebral mass, aneurysm, arteriovenous malformation, hemorrhagic stroke, or gastrointestinal or genitourinary bleeding within the preceding 2 weeks; platelet count <100,000/mm3 at baseline or history of heparin induced thrombocytopenia; baseline INR >1.5 times control; treatment with bivalirudin, thrombolytic therapy, fondaparinux, abciximab, another GP IIb/IIIa inhibitor that cannot be
discontinued, or ≥2 doses of LMWH for the current admission; calculated creatinine clearance <30 ml/min; absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast or to any of the study medications.

Primary Endpoints:

1) Composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days; 2) Composite of death, myocardial infarction, and unplanned revascularization for ischemia at 30 days; 3) Major bleeding at 30 days

Drug/Procedures Used:

Patients were randomized to unfractionated heparin (UFH) or enoxaparin plus a GP IIb/IIIa inhibitor (n=4603), bivalirudin plus a GP IIb/IIIa inhibitor (n=4604), or bivalirudin alone (n=4612). In the last arm, GP IIb/IIIa inhibitors could be used when needed for "bailout" with sub-optimal results. In the first two arms, patients underwent a second randomization to either GP IIb/IIIa inhibitor administration upstream prior to angiography or during PCI. Patients then underwent cardiac catheterization within 72 hours with either percutaneous coronary intervention (PCI), surgical revascularization or medical therapy.

Concomitant Medications:

Aspirin; clopidogrel was recommended but not mandated

Principal Findings:

Cardiac enzymes (troponin or CKMB) were elevated at baseline in 59% of patients. Diabetes was present in 28% of patients. Management strategy following catheterization was largely PCI (56%) followed by medical therapy (33%) and CABG (11%). Median time from start of study drug to angiography was ~4 hours.

The primary net clinical benefit was significantly improved in the bivalirudin alone group compared with the UFH / Enox plus GP IIb/IIIa group (10.1% vs 11.7%, p=0.015 for superiority). The bivalirudin plus GP IIb/IIIa inhibitor group met the criteria for non-inferiority compared with the UFH / Enox plus GP IIb/IIIa group (11.8% vs 11.7%, p<0.001 for non-inferiority). Compared with the heparin plus GP IIb/IIIa group (7.3%), the composite ischemic endpoint was non-inferior for the bivalirudin alone group (7.8%, p=0.01) and the bivalirudin plus GP IIb/IIIa group (7.7%, p=0.007) but did not reach superiority for any comparison. Major bleeding was significantly lower in the bivalirudin alone group compared with the heparin plus GP IIb/IIIa group (3.0% vs 5.7%, p<0.001 for superiority), and was non-inferior but not superior for the comparison of bivalirudin plus GP IIb/IIIa inhibitor with the UFH / Enox plus GP IIb/IIIa group (5.3% vs 5.7%, p=0.001 for non-inferiority). Results were similar when using the TIMI major bleeding criteria (1.9% for UFH / Enox plus GP IIb/IIIa, 1.7% for bivalirudin plus GP IIb/IIIa, 0.9% for bivalirudin alone, p<0.001 for superiority of bivalirudin vs UFH / Enox plus GP IIb/IIIa.

Interpretation:

Among patients with acute coronary syndromes, treatment with bivalirudin alone was associated with a reduction in the net clinical benefit endpoint compared with UFH/Enox plus GP IIb/IIIa inhibitors, driven primarily by a reduction in bleeding. Additionally, bivalirudin plus a GP IIb/IIIa inhibitor was shown to be non-inferior for the net clinical benefit endpoint compared with UFH/Enox plus GP IIb/IIIa inhibitor.

References:

Stone GW, et al. Bivalirudin for Patients with Acute Coronary Syndromes. N Engl J Med 2006;355:2203-16.

Presented by Dr. Gregg W. Stone at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Homozygous Familial Hypercholesterolemia, Heart Failure and Cardiac Biomarkers, Interventions and ACS, Interventions and Coronary Artery Disease, Hypertension

Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Cardiac Catheterization, Heparin, Hypercholesterolemia, Hirudins, Platelet Membrane Glycoprotein IIb, Percutaneous Coronary Intervention, Enoxaparin, Recombinant Proteins, Peptide Fragments, Hypertension, Diabetes Mellitus, Troponin, Platelet Glycoprotein GPIIb-IIIa Complex


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