It was stated in the article by Macie et al1 that previous randomized controlled trials (RCTs) have limitations in addressing practical issues that may impact on bleeding risk in the real-world population, because of the exclusion of patients weighing > 100 kg. First, the prespecified definition of obesity should use body mass index (BMI), because body weight alone is not always an accurate reflection of obesity. For example, the heaviest weight recorded in the Thrombolysis in Myocardial Infarction (TIMI) 11B10and Efficacy and Safety of Subcutaneous Enoxaparin in NonQ-Wave Coronary Events (ESSENCE)11 databases for a nonobese patient is 110 kg. Second, it is untrue that other studies have not researched patients weighing > 100 kg: in the meta-analysis of the TIMI 11B and ESSENCE trials comparing the safety and efficacy of a weight-adjusted dose of enoxaparin and unfractionated heparin (UFH) in obese patients (n = 7,081), approximately 26% of patients in the trial were obese (defined as BMI ≥ 30), thereby providing a large sample size for comparison.6 The maximum weight of patients treated with enoxaparin in this meta-analysis was 158.6 kg. Of these patients, 540 patients weighed > 100 kg (n = 275 UFH, n = 265 enoxaparin). Statistical analysis on this subgroup showed no significant difference between the UFH and enoxaparin groups in either the double or triple end points (incidence of death and myocardial infarction and/or urgent revascularization). Meanwhile, the maximum weight of patients in the Superior Yield of the New strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa inhibitors (SYNERGY) trial,12which evaluated the effect of enoxaparin and UFH on death and myocardial infarction in high-risk patients presenting with non–ST-segment elevation ACS (n = 10,027), was 175 kg in the UFH group and 196 kg in the enoxaparin group, while the interquartile range was 70 to 91 kg for both groups—the highest weights for any ACS trial to date. There were no inclusion/exclusion criteria related to weight, and dosing was 1 mg/kg for all patients. Recent preliminary results from the SYNERGY trial have shown no evidence of differing efficacy or safety between 1 mg/kg weight-adjusted enoxaparin and UFH in the obese subgroup (K.W. Mahaffey, MD; personal communication; September 24, 2004). To our knowledge, there has only been one clinical trial13 of enoxaparin in patients with ACS where there was a weight cutoff at 110 kg. Third, the studies referenced for this statement are a pharmacodynamic study of tinzaparin and a pharmacokinetic study on the effect of weight and LMWH in the treatment of venous thromboembolism (ie, no ACS patients).