March 22, 2006|
Jennifer Tartaglia MS and Asher Kimchi M.D.
Ontario, Canada -
Anticoagulants, antiplatelet agents, and invasive
coronary procedures reduce ischemic coronary events
in patients with acute coronary syndromes, but
increase bleeding. Enoxaparin is a low molecular
weight heparin commonly used in patients with acute
coronary syndromes that reduces their risk of death
or myocardial infarction (MI). A trial conducted by
the Fifth Organization to Assess Strategies in Acute
Ischemic Syndromes Investigators (OASIS-5) in
Ontario, Canada compared the efficacy and safety of
fondaparinux (Arixtra) and enoxaparin (Lovenox). The
trial found that fondaparinux is similar to
enoxaparin in reducing the risk of ischemic coronary
events and it significantly decreases major
bleeding. These results were published in the March
14, 2006 issue of The New England Journal of
The study was randomized, double-blind, and double-dummy. It
enrolled 20,078 patients with unstable angina or myocardial
infarctions (MIs) without ST segment elevation. These
participants were randomly assigned to receive fondaparinux
2.5mg daily and placebo enoxaparin bid or to receive enoxaparin
1mg per kg of body weight bid and placebo fondaparinux daily.
Patients were followed for 90-180 days.
The primary study finding was that death, MI, or refractory
ischemia at 9 days (primary outcome events) was not
significantly different between fondaparinux (5.8%) and
enoxaparin (5.7%; Hazard ratio (HR), 1.01; 95% confidence
interval (CI), 0.90-1.13). In addition, fondaparinux was more
effective at decreasing mortality after 30 days (2.9%) when
compared with enoxaparin (3.5%; HR, 0.83; 95% CI, 0.71-0.97;
P=0.02). Fondaparinux also substantially decreased the rate of
major bleeding at 9 days (2.2%) when compared with enoxaparin
(4.1%; HR, 0.52; 95% CI, 0.44-0.61; P<0.001). The investigators
found the composite of death, MI, refractory ischemia, or major
bleeding at 9 days in 7.3% of patients in the fondaparinux
group, as compared with 9.0% of patients in the enoxaparin group
(HR, 0.81; 95% CI, 0.73-0.89; P<0.001).
These findings suggest that fondaparinux, while having a
similar efficacy to enoxaparin, has significantly less bleeding,
which is associated with lower long-term mortality and
morbidity. This increased bleeding seen with enoxaparin is
thought to be due to the drug’s intrinsic properties associated
with the inhibition of thrombin in combination with a current
recommended dose of enoxaparin that may be too high.
Consequently, the authors recommend using fondaparinux as an
alternative to enoxaparin in the short-term care of patients
with acute coronary syndromes.
Authors (The Writing Committee): Salim Yusuf, D.Phil., M.B.,
B.S., Shamir R. Mehta, M.D., Susan Chrolavicius, B.A., Rizwan
Afzal, M.Sc., Janice Pogue, M.Sc., Christopher B. Granger, M.D.,
Andrzej Budaj, Ph.D., Ron J.G. Peters, M.D., Jean-Pierre Bassand,
M.D., Lars Wallentin, Ph.D., Campbell Joyner, M.D., and Keith
A.A. Fox, F.R.C.P.