• Interventional Techniques & Devices Cardiology Clinical Trials
• Thrombotic Disorders

The addition of a standard-dose regimen of unfractionated heparin (UFH) to fondaparinux (FONDA) during percutaneous coronary intervention (PCI) preserves the bleeding reduction benefit of fondaparinux therapy while minimizing associated catheter thrombosis risk in patients with acute coronary syndromes (ACS). However, a low-dose UFH regimen did not reduce the rate of major peri-PCI bleeding or major vascular access site complications compared with standard-dose UFH when added to FONDA treatment in this cohort. Sanjit S. Jolly, MD, McMaster University, Hamilton, Ontario, Canada, presented findings from the Fondaparinux Trial with Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA)/Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-8 Study (NCT00790907).

FONDA was determined to reduce major bleeding and improve long-term morbidity and mortality rates compared with enoxaparin in OASIS-5. However, catheter thrombosis was more common among patients who were treated with FONDA compared with enoxaparin alone, and this risk appeared to be attenuated by adjunct UFH during PCI [OASIS-5 Investigators. N Engl J Med 2006; Mehta SR et al. J Am Coll Cardiol 2007]. FUTURA/OASIS-8 was designed to compare the safety of 2 UFH regimens in patients who were undergoing PCI (within 72 hours) who had non-ST-segment elevation ACS and had been treated with FONDA.

Patients were randomized to receive either intravenous low-dose (50 U/kg; n=1024) or standard-dose (85 U/kg or 60 U/kg if taking glycoprotein IIb/IIIa inhibitors; n=1002) UFH, adjusted by blinded activated clotting time. The primary outcome was the composite of major bleeding, minor bleeding, or major vascular access site complications within 48 hours of PCI (Table 1). Key secondary outcomes included the composite of major bleeding within 48 hours of PCI with death, myocardial infarction (MI), or target vessel revascularization (TVR) within 30 days.

The rates that were associated with the composite primary outcome were similar for both UFH groups. Analysis of individual primary outcome components revealed similar rates between the two groups, with the exception of minor bleeds, which was lower in the low-dose UFH group (0.7% vs 1.7% in the standard group; p=0.04). The secondary composite outcome of peri-PCI major bleeding with death, MI, or TVR at 30 days favored the standard UFH regimen over low-dose UFH (3.9% for standard vs 5.8% for low-dose; OR, 1.51; 95% CI, 1.00 to 2.28; p=0.05). The rate of death, MI, or TVR at 30 days was also lower in the standard-dose group (2.9%) than in the low-dose group (4.5%; p=0.06). Catheter thrombus rates were low in both treatment groups (0.5% vs 0.1% in the standard-dose group).

The FUTURA/OASIS-8 results confirm the strength of current guidelines that recommend the standard-dose regimen of UFH during PCI. There was no significant difference in major bleeding or vascular complication between the two doses of UFH. The use of UFH in patients with ACS who are treated with FONDA who are undergoing PCI appears to be safe, but current UFH dose recommendations should be followed. It is important to note that patients who required urgent (<120 minutes) coronary angiography were excluded from participation in this study, which may have resulted in a lower-risk study population. Additionally, the study was not powered to fully compare the doses with regard to ischemic events alone, which influences the bleeding-versus-thrombotic risk assessment. Therefore, caution should be used when interpreting these data.

FUTURA/OASIS-8 was published online ahead of print JAMA August 31, 2010.

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