Reply

Pechlaner et al. suggest that our findings (1)of less rebound ischemia with enoxaparin as compared to unfractionated heparin (UFH) are simply due to the longer half-life of enoxaparin. However, the ischemic episodes (average number and duration) identified during continuous electrocardiographic monitoring were statistically significantly lower in the enoxaparin as compared to the UFH group not only during the first 12 h after drug discontinuation but also during the >12 to 24-h and even the >36 to 48-h time intervals. This suggests that the benefit seen with enoxaparin is not simply due to prolonged half-life and greater anti-Xa:IIa activity that “wanes” more slowly than UFH. Indeed, there is growing evidence supporting additional mechanisms of benefit of enoxaparin over UFH beyond the differences in pharmacokinetics; for example, the significant blunting of the rise of von Willebrand factor with enoxaparin in the first 48 h of treatment (2).

As we noted, our substudy (1)was stopped at the time of overall trial completion but prior to enrollment of an adequately powered sample size to confidently address the initial 48-h period of active treatment. Nonetheless, among the subgroup of patients who underwent monitoring during both the initial treatment and study drug discontinuation periods (n = 163), ischemia was less frequently observed during bothmonitoring periods in the enoxaparin group (18.4% vs. 32.2%, p = 0.045 and 25% vs. 46%, p = 0.005, respectively). Further, the time to first ischemic episode was significantly earlier among UFH-treated patients, consistent with a superior earlyantithrombotic effect of enoxaparin and a reduction in the composite clinical end point of death, myocardial infarction (MI), and need for urgent revascularization (3).

Therefore, we believe that enoxaparin has been shown to be superior to UFH based upon the consistent and statistically significant reductions in the composite and double (death/MI) end points in ESSENCE and TIMI 11B (4). In contrast, “extending the duration and slower weaning” of UFH is an unproven method of administration, and, in fact, the cost-savings realized with enoxaparin ultimately make it the lessexpensive option (5).

• American College of Cardiology