Comparative effectiveness research in action: enoxaparin versus fondaparinux for acute coronary syndrome

From a recent systematic review:

Results

Seven studies with a total number of 9618 patients (mainly composed of non-ST elevated myocardial infarction/NSTEMI) were included. This analysis showed mortality to be similarly observed between enoxaparin and fondaparinux with OR: 1.05, 95% CI: 0.67–1.63; P = 0.84. Myocardial infarction (MI) and stroke were also not significantly different throughout different follow up periods. However, minor, major and total bleeding were significantly lower with fondaparinux (OR: 0.40, 95% CI: 0.27–0.58; P = 0.00001), (OR: 0.46, 95% CI: 0.32–0.66; P = 0.0001) and (OR: 0.47, 95% CI: 0.37–0.60; P = 0.00001) respectively during the 10-day follow up period. Even during a follow up period of 30 days or a midterm follow up, major and minor bleeding still significantly favored fondaparinux in comparison to enoxaparin.

Conclusion

In patients who were treated for ACS, fondaparinux might be a better choice when compared to enoxaparin in terms of short to midterm bleeding events. This result was mainly applicable to patients with NSTEMI. However, due to a limited number of patients analyzed, further larger randomized trials should be able to confirm this hypothesis.

The reduced bleeding risk likely has to do with dosing, as I once explained here:

It would appear that the improved outcome was driven by a reduction in bleeding with fondaparinux. I think this relates to the fact that for acute coronary syndrome fondaparinux is administered in the same dose as is used for VTE prophylaxis rather than in a full therapeutic anticoagulation dose.

And, depending on the patient’s body weight, that ACS dose could amount to half, one third or even a quarter the VTE treatment dose. This usage for ACS, while validated in clinical trials, remains off label in the US. This indication based difference in dosing for fondaparinux is similar to that with unfractionated heparin where the ACS dose is lower than the VTE treatment dose. Though enoxaparin is used in the same dose for VTE and ACS treatment, for all we know it might be effective for ACS at a lower dose but as far as I know it has not been studied in that manner.