We thank Drs. Famularo and Minisola for their comments, but it is important to note that the dose of enoxaparin used in our study was the dose approved by regulatory agencies and recommended by acute coronary syndrome guidelines. To optimize both safety and efficacy, we chose the dose of fondaparinux on the basis of the PENTUA (Pentasaccharide in Unstable Angina) trial, a phase II study in patients with acute coronary syndromes, and other data. Using the "full dose" of an experimental drug may not be appropriate when the goal is to minimize bleeding risk yet provide appropriate efficacy. Our findings suggest that similar considerations need to be applied to the dose selection of enoxaparin, and that, especially in patients with moderate or more severe renal dysfunction, a lower dose may provide a better balance between efficacy and safety. This is speculative, however, and has yet to be proven in randomized trials.

In addition to renal function and patient risk features, age and many other factors, such as direct antithrombin activity or the binding to endothelial cells and plasma proteins, should be considered in relation to bleeding risk. In the OASIS-6 trial (1), the lack of an increase in cases of bleeding with fondaparinux versus placebo (in stratum 1) or unfractionated heparin (in stratum 2) is noteworthy, because a significant reduction in mortality and re-infarction and a trend toward fewer strokes occurred. The results of both OASIS-5 and OASIS-6 reinforce the concept that efficacy benefits can be achieved without compromising patient safety.