Synthetic inhibitors of activated factor Xa prevent clot formation. To
assess whether the factor-Xa inhibitor fondaparinux is as safe and
effective as enoxaparin for patients with deep-vein thrombosis, these
authors conducted a multicenter, randomized, double-blind,
placebo-controlled, manufacturer-supported trial. Because fondaparinux
can be given once daily, its use would simplify DVT treatment.

Of 5141 consecutive adult patients with lower-extremity DVT, more than
half were excluded for reasons including pulmonary embolism,
therapeutic anticoagulation therapy for more than 24 hours,
thrombolytic therapy, and vena cava filter. A total of 2205 patients
were randomized to receive fondaparinux once daily (5.0, 7.5, or 10
mg, depending on body weight) or enoxaparin twice daily (1 mg/kg) for
5 days or until the international normalized ratio was at least 2.0.
To maintain blinding, patients received placebo injections once daily
(enoxaparin group) or twice daily (fondaparinux group). The primary
efficacy outcome was recurrence of venous thrombosis, including PE,
within 90 days. Safety outcomes were bleeding during initial treatment
and death within 90 days.

Outcomes were similar in the fondaparinux and enoxaparin groups, both
overall and in a subset of patients who were treated at home. Venous
thrombosis recurred in 3.9% of fondaparinux recipients and 4.1% of
enoxaparin recipients. During initial treatment, two patients in the
fondaparinux group and none in the enoxaparin group died, but the two
groups had similar 90-day mortality rates (3.8% and 3.0%). Major
bleeding during initial treatment occurred in 1.1% and 1.2% of the two
groups, respectively. Of note, unlike the availability of protamine
for reversing the effects of heparin, there is no specific antidote to
the synthetic coagulation inhibitors.

Comment: The availability of a once-daily-dose, effective
antithrombotic agent administered by prefilled syringe clearly would
simplify effective at-home treatment for DVT, reducing not only
hospital admissions but also the education portion of the emergency
department visit that variable doses require. Supervisory visits by
visiting nurses could also be reduced. The authors did not report
relative costs of the agents, and possible reductions in ED
length-of-stay; use of nursing and physician resources must still be
elucidated.

— J. Stephen Bohan, MS, MD, FACP, FACEP

Published in Journal Watch Emergency Medicine June 30, 2004

Source

Buller HR et al.. Fondaparinux or enoxaparin for the initial treatment
of symptomatic deep venous thrombosis: A randomized trial. Ann Intern
Med 2004 Jun 1; 140:867-73.
[Original article][Medline abstract][Download citation]