The Fondaparinux Trial With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes/OASIS-8 - FUTURA/OASIS-8

Aug 31, 2010
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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:
GlaxoSmithKline
Date Presented:
01/01/2010
Date Published:
01/01/2010
Date Updated:
08/31/2010
Original Posted Date:
08/31/2010
References

Description:

The goal of the trial was to evaluate treatment with low-dose unfractionated heparin (UFH) compared with standard-dose UFH among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) treated on a background of fondaparinux therapy.

Hypothesis:

Low-dose heparin will prevent major/minor bleeding/access site complications.

Study Design

  • Blinded
  • Parallel
  • Randomized

Patient Populations:

  • Patients with NSTE-ACS and two of the following:
    Age >60 years
    Elevated biomarkers
    Electrocardiogram changes

    Number of enrollees: 2,026
    Duration of follow-up: 30 days
    Mean patient age: 65 years
    Percentage female: 33%

Exclusions:

  • Clinical instability

Primary Endpoints:

  • Major bleeding, minor bleeding, or major vascular access site complication at 48 hours

  • Major bleeding defined per OASIS 5:
    Fatal bleed
    Intracranial hemorrhage
    Retroperitoneal hemorrhage
    Intraoccular hemorrhage
    Bleed requiring surgical intervention
    Hemoglobin drop ≥3 g/dl
    Blood transfusion ≥2 units packed red blood cells

  • Minor bleeding defined per OASIS 5:
    Any other bleed that results in 1 unit packed red blood cell transfusion or discontinuation of antithrombotic therapy

  • Major vascular access site complication defined as:
    Large hematoma (5 cm)
    Pseudoaneurysm
    Arteriovenous fistula
    Other vascular surgery related to access site

Secondary Endpoints:

  • Major bleeding, death, MI, or revascularization at 30 days

Drug/Procedures Used:

Patients with NSTE-ACS treated on a background of subcutaneous fondaparinux 2.5 mg were randomized to low-dose UFH 50 U/kg regardless of glycoprotein inhibitor IIb/IIIa use (n = 1,024) versus standard-dose UFH 60 U/kg with glycoprotein IIb/IIIa inhibitor or 85 U/kg without glycoprotein inhibitor IIb/IIIa (n = 1,002).

Concomitant Medications:

At baseline in the low-dose heparin group, the use of aspirin was 95%, and clopidogrel was 95%.

Principal Findings:

Overall, 2,026 patients were randomized. In the low-dose heparin group, the mean age was 65 years, 33% were women, 26% had diabetes, 81% had an elevated troponin T or I, femoral access was used in 64% of cases, duration of fondaparinux was 3 days, and time from last dose of fondaparinux to percutaneous coronary intervention (PCI) was 4 hours and 26 minutes.

At 48 hours, the primary outcome of major bleeds/minor bleeds/vascular access site complications occurred in 4.7% of the low-dose heparin group versus 5.8% of the standard-dose heparin group (p = 0.27). Major bleeds were 1.4% versus 1.2%, minor bleeds were 0.7% versus 1.7% (p = 0.04), and major vascular access site complications were 3.2% versus 4.3% (p = 0.21), respectively.

At 30 days, major bleeding, death, myocardial infarction (MI), or revascularization occurred in 5.8% versus 3.9% (p = 0.05), death, MI, or revascularization occurred in 4.5% versus 2.9% (p = 0.06), death occurred in 0.8% versus 0.6%, MI occurred in 3.0% versus 2.5%, revascularization occurred in 0.9% versus 0.3%, stent thrombosis occurred in 1.2% versus 0.5% (p = 0.11), and catheter thrombosis occurred in 0.5% versus 0.1% (p = 0.15), respectively.

Interpretation:

Among ACS patients initially treated with fondaparinux, PCI can be safely performed with the addition of UFH. Low-dose and standard-dose heparin had the same frequency of bleeding events (and similar to the frequency in the initial OASIS 5 trial); however, low-dose heparin therapy was associated with a marginally significant increase in ischemic events. While data support that ischemic events are increased with reduced dosage of heparin, the optimal target that will result in the lowest ischemic/bleeding events is unknown.

References:

The FUTURA/OASIS-8 Trial Group. Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux: The FUTURA/OASIS-8 Randomized Trial. JAMA 2010;Aug 31:[Epub ahead of print]. 

 Presented by Dr. Sanjit Jolly at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

Keywords: Polysaccharides, Myocardial Infarction, Acute Coronary Syndrome, Thrombosis, Heparin, Troponin T, Electrocardiography, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention


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