Antithrombotic Strategies in Patients With Acute Coronary Syndromes Undergoing Early Invasive Management - ACUITY: 1-Year Results

Dec 12, 2007
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
The Medicines Company; Nycomed
Date Presented:
01/01/2007
Date Published:
01/01/2007
Date Updated:
12/12/2007
Original Posted Date:
12/12/2007
References

Description:

The goal of this study was to report long-term follow-up from the use of one of three antithrombotic regimens in the management of acute coronary syndromes (ACS): 1) heparin and a glycoprotein (GP) IIb/IIIa inhibitor, 2) bivalirudin and a GP IIb/IIIa inhibitor, or 3) bivalirudin alone.

Hypothesis:

Bivalirudin, with or without a GP IIb/IIIa inhibitor, produces similar long-term results to heparin and a GP IIb/IIIa inhibitor in the management of ACS patients.

Study Design

  • Factorial
  • Stratified

Mean Follow Up: 335-395 days
Mean Patient Age: 63 years
Female: 30

Patient Populations:

Patients were considered for the randomization if they were at least 18 years of age and had an episode of an acute coronary syndrome that lasted at least 10 minutes within the preceding 24 hours. An acute coronary syndrome was defined by at least one of the following Thrombolysis in Myocardial Infarction (TIMI) risk score variables: 1) dynamic electrocardiographic changes such as ST-depression or transient ST-elevation, 2) elevated cardiac biomarkers such as troponin (I or T) or creatine kinase-MB isoenzyme, or 3) history of coronary artery disease. The presence of all four of the remaining variables of the TIMI risk score was also considered an ACS.

Exclusions:

Patients were excluded if they were younger than 18 years, presented with ST-elevation myocardial infarction, cardiogenic shock, recent bleed, bleeding abnormality or thrombocytopenia, renal insufficiency, or the use of Coumadin, fibrinolytics, abciximab, or fondaparinux during the index hospitalization. Patients were also excluded if they received at least two doses of low molecular weight heparin or bivalirudin within 6 hours of randomization.

Primary Endpoints:

The primary endpoint was a composite of death, myocardial infarction, or unplanned revascularization at 1 year of follow-up.

Drug/Procedures Used:

Patients who presented within 24 hours from the onset of an ACS were randomized to: 1) heparin and a GP IIb/IIIa inhibitor (n = 4,603), 2) bivalirudin and a GP IIb/IIIa inhibitor (n = 4,604), or 3) bivalirudin alone (n = 4,612).

Principal Findings:

The incidence of the primary outcome at 1 year was 15.4% in the heparin and GP IIb/IIIa inhibitor group, 16.0% in the bivalirudin and GP IIb/IIIa inhibitor group, and 16.2% in the bivalirudin alone group. The hazard ratio (HR) (95% confidence interval) for bivalirudin and a GP IIb/IIIa inhibitor, compared with heparin and a GP IIb/IIIa inhibitor, was 1.05 (0.95-1.16) and 1.06 (0.95-1.17) for the bivalirudin alone group. The incidences of the individual components of the composite outcome were all similar, except for non-Q-wave myocardial infarction, where the incidence was 6.4% in the bivalirudin alone group, compared with 5.4% in the heparin and a GP IIb/IIIa inhibitor group (HR 1.18 [0.99-1.40]).

Prespecified subgroup analyses for the primary composite outcome were all nonsignificant; however, they tended to favor heparin and a GP IIb/IIIa inhibitor. Subgroup analyses for mortality were also nonsignificant; however, they generally tended to favor bivalirudin alone. Considering the timing of a GP IIb/IIIa inhibitor, the incidence of composite ischemia was 16.3% with deferred use, compared to 15.2% with routine upstream use (HR 1.08 [0.97-1.20]). The incidence of mortality was 4.0% with deferred use and 3.8% with routine upstream use (HR 1.05 [0.85-1.29]).

Interpretation:

This study builds on the results of the 30-day ACUITY trial, which showed that bivalirudin with or without a GP IIb/IIIa inhibitor was noninferior to heparin and a GP IIb/IIIa inhibitor in reducing ischemic events. That study also showed that bivaluridin alone significantly reduced major bleeding, compared with the regimens that included a GP IIb/IIIa inhibitor. Although the present study was not specifically designed to show noninferiority, it does confirm the similarity of these three regimens in the incidence of composite ischemia at 1 year. Long-term bleeding was not assessed in the present study.

Despite the benefit afforded from bivalirudin alone in reducing major bleeding within 30 days, this did not translate into a survival advantage by 1 year. One hypothesis is that bivalirudin alone results in less bleeding, although this might be offset by slightly more ischemic events, in particular periprocedural myocardial infarction. When a GP IIb/IIIa inhibitor is used, deferred use after coronary angiography is performed appears to produce similar results to routine upstream use. This finding may not apply to patients with recurrent/refractory ischemia or when there is a long delay to cardiac catheterization. Overall, bivalirudin with provisional use of a GP IIb/IIIa inhibitor results in similar long-term ischemic efficacy compared with heparin and a GP IIb/IIIa inhibitor.

References:

Stone GW, et al. Antithrombotic strategies in patients With acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial. JAMA 2007;298:2497-2506.

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Coronary Artery Disease, Cardiac Catheterization, Creatine Kinase, MB Form, Heparin, Platelet Membrane Glycoprotein IIb, Hirudins, Coronary Angiography, Troponin I, Recombinant Proteins, Peptide Fragments, Platelet Glycoprotein GPIIb-IIIa Complex


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