Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial.
OBJECTIVE
This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.


BACKGROUND
In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%.


METHODS
The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h.


RESULTS
Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding.


CONCLUSIONS
Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.
Mehta
Shamir R
SR
Department of Medicine, McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. smehta@mcmaster.ca
Granger
Christopher B
CB
Eikelboom
John W
JW
Bassand
Jean-Pierre
JP
Wallentin
Lars
L
Faxon
David P
DP
Peters
Ron J G
RJ
Budaj
Andrzej
A
Afzal
Rizwan
R
Chrolavicius
Susan
S
Fox
Keith A A
KA
Yusuf
Salim
S
D000789:Angina, Unstable / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000627:therapeutic use*; D015331:Cohort Studies; D004311:Double-Blind Method; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D011134:Polysaccharides / Q000627:therapeutic use*; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome
D000925:Anticoagulants; D017984:Enoxaparin; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux