Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes.
BACKGROUND
A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding.


OBJECTIVE
To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial.


METHODS
Subgroup analysis of a randomized, controlled trial.


METHODS
Patients presenting to the hospital with non-ST-segment elevation ACS.


METHODS
19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline.


METHODS
Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula.


RESULTS
The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2.


CONCLUSIONS
Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States.


CONCLUSIONS
The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.
Fox
Keith A A
KA
Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom. k.a.a.fox@ed.ac.uk
Bassand
Jean-Pierre
JP
Mehta
Shamir R
SR
Wallentin
Lars
L
Theroux
Pierre
P
Piegas
Leopoldo Soares
LS
Valentin
Vicent
V
Moccetti
Tiziano
T
Chrolavicius
Susan
S
Afzal
Rizwan
R
Yusuf
Salim
S
D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000209:etiology; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004311:Double-Blind Method; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077425:Fondaparinux; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D011134:Polysaccharides / Q000009:adverse effects / Q000627:therapeutic use*; D013577:Syndrome