Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.
BACKGROUND
The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin).


OBJECTIVE
To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis.


METHODS
Randomized, double-blind study.


METHODS
154 centers worldwide.


METHODS
2205 patients with acute symptomatic deep venous thrombosis.


METHODS
Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0.


METHODS
The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes.


RESULTS
43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.


CONCLUSIONS
Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients.


CONCLUSIONS
Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.
Büller
Harry R
HR
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Davidson
Bruce L
BL
Decousus
Hervé
H
Gallus
Alexander
A
Gent
Michael
M
Piovella
Franco
F
Prins
Martin H
MH
Raskob
Gary
G
Segers
Annelise E M
AE
Cariou
Roger
R
Leeuwenkamp
Oscar
O
Lensing
Anthonie W A
AW
D000368:Aged; D001835:Body Weight; D002423:Cause of Death; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012008:Recurrence; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000401:mortality; D014812:Vitamin K / Q000037:antagonists & inhibitors
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D014812:Vitamin K; D000077425:Fondaparinux