Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.
OBJECTIVE
This study sought to evaluate the relative safety and efficacy of fondaparinux and enoxaparin in patients with acute coronary syndromes (ACS) treated with glycoprotein (GP) IIb/IIIa inhibitors or thienopyridines.


BACKGROUND
The OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial showed that fondaparinux reduced major bleeding by 50% compared with enoxaparin while preserving similar efficacy. Whether this benefit is consistent in the presence or absence of concurrent antiplatelet therapy with clopidogrel and GP IIb/IIIa inhibitors is unknown.


METHODS
Patients with ACS (n = 20,078) were randomized as a part of the OASIS 5 trial to receive either fondaparinux or enoxaparin. The use of GP IIb/IIIa inhibitors or thienopyridines was at the discretion of the treating physician. A Cox proportional hazard model was used to compare outcomes.


RESULTS
Of the 20,078 patients randomized, 3,630 patients received GP IIb/IIIa and 13,531 received thienopyridines. There was a 40% reduction in major bleeding with fondaparinux compared with enoxaparin in those treated with GP IIb/IIIa (5.2% vs. 8.3%, hazard ratio [HR]: 0.61, p < 0.001). A similar reduction was found in those treated with thienopyridines (3.4% vs. 5.4%, HR: 0.62, p < 0.001). Ischemic events were similar between the groups, resulting in a superior net clinical outcome (death, myocardial infarction, refractory ischemia, or major bleeding) favoring fondaparinux (GP IIb/IIIa subgroup 14.8% vs. 18.9%, HR: 0.77, p = 0.001 and thienopyridines subgroup 11.0% vs. 13.2%, HR: 0.82, p < 0.001).


CONCLUSIONS
In patients receiving GP IIb/IIIa inhibitors or thienopyridines, fondaparinux reduces major bleeding and improves net clinical outcome compared with enoxaparin.
Jolly
Sanjit S
SS
Department of Medicine, Hamilton Health Sciences, Population Health Research Institute, McMaster University, McMaster Clinic Room 630, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada. jollyss@mcmaster.ca
Faxon
David P
DP
Fox
Keith A A
KA
Afzal
Rizwan
R
Boden
William E
WE
Widimsky
Petr
P
Steg
P Gabriel
PG
Valentin
Vicent
V
Budaj
Andrez
A
Granger
Christopher B
CB
Joyner
Campbell D
CD
Chrolavicius
Susan
S
Yusuf
Salim
S
Mehta
Shamir R
SR
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000077425:Fondaparinux; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000925:Anticoagulants; D017984:Enoxaparin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011134:Polysaccharides; D011725:Pyridines; C446540:thienopyridine; D000077425:Fondaparinux