Patients with acute coronary syndrome and on Fondaparinux: safety of two intravenous Heparin doses as adjunct to PCI


Results from the FUTURA/OASIS 8 study provide initial evidence that a low dose of unfractionated Heparin does not reduce the incidence of bleeding or vascular complications in PCI ( percutaneous coronary intervention ) patients treated with the anticoagulant Fondaparinux ( Arixtra ). Findings showed that the rates of peri-PCI major bleeding were 1.4% in those given low dose Heparin and 1.2% the standard dose.

An earlier trial, OASIS 5 had shown that anticoagulation with Fondaparinux was more effective in reducing mortality and serious bleeding rates in post-MI patients than with Enoxaparin ( Lovenox ). However, rates of catheter thrombosis during angioplasty with Fondaparinux were found to be higher than with Enoxaparin, which prompted the adjunctive use of unfractionated Heparin to prevent clotting in patients treated with Fondaparinux. However there was uncertainty about the optimal dose.

FUTURA/OASIS 8, designed to resolve that uncertainty, was a phase 3, multicentre, randomised trial in 2026 patients undergoing PCI within 72 hours of hospital admission for unstable angina or myocardial infarction. As soon as possible after arrival, they received Fondaparinux 2.5 mg daily, and those requiring PCI were randomised to low fixed dose Heparin ( 50 U/kg ) or standard dose Heparin ( 85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors ).

The primary outcome was a composite of peri-PCI major bleeding, minor bleeding or major vascular complications, and results showed there was no difference between the two dose regimes in this endpoint. However, while the low dose regimen did not lower the risk of major bleeding, it did lower minor bleeding rates by 60%. And there was also a trend towards higher risk of death, myocardial infarction or target vessel revascularisation ( secondary endpoint ) with the lower dose. The rates of catheter thrombosis were very low in both groups ( 0.5% and 0.1% in the low and standard dose respectively ).

It was also noted that the rates of major bleeding in FUTURA-OASIS 8 ( 1.4% low dose and 1.2% standard dose ) were not significantly different from that observed in the Fondaparinux arm of the OASIS 5 trial ( 1.5% ) but lower than in the Enoxaparin arm ( 3.6% ).

In conclusion, the standard dose of unfractionated Heparin may be the optimal treatment strategy in PCI patients on Fondaparinux, while maintaining the major advantage of Fondaparinux which is a low rate of major bleeding.

Source: European Society of Cardiology Meeting, 2010

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