Randomized, blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: Arixtra Study in Percutaneous Coronary Intervention: a Randomized Evaluation (ASPIRE) Pilot Trial.
BACKGROUND
Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting.


RESULTS
A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02).


CONCLUSIONS
In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.
Mehta
Shamir R
SR
McMaster University and the Population Health Research Institute, Hamilton Health Sciences, General Division, 237 Barton St E, Hamilton, Ontario, Canada L6K 1B8. smehta@mcmaster.ca
Steg
Philippe Gabriel
PG
Granger
Christopher B
CB
Bassand
Jean-Pierre
JP
Faxon
David P
DP
Weitz
Jeffrey I
JI
Afzal
Rizwan
R
Rush
Bonnie
B
Peters
Ron J G
RJ
Natarajan
Madhu K
MK
Velianou
James L
JL
Goodhart
David M
DM
Labinaz
Marino
M
Tanguay
Jean-Francois
JF
Fox
Keith A A
KA
Yusuf
Salim
S
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004630:Emergencies; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D005260:Female; D000077425:Fondaparinux; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D010865:Pilot Projects; D011134:Polysaccharides / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D015607:Stents; D016896:Treatment Outcome
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux