Hazards of using enoxaparin in patients with reduced creatinine clearance but above the threshold for dose adjustment

From a recent paper in JAMA Internal Medicine:

Methods Patients received enoxaparin sodium, 1 mg/kg, every 12 hours or 1.5 mg/kg once daily between June 1 and November 30, 2009. Moderate renal impairment was defined as creatinine clearance (CrCl) of 30 to 50 mL/min. Normal renal function was defined as CrCl greater than 80 mL/min. The primary outcome was major bleeding, defined as any bleeding resulting in death, hospital admission, lengthened hospital stay, or an emergency department visit. The secondary outcome was thromboembolism.

Results A total of 164 patients met the inclusion criteria: 105 with normal renal function and 59 with moderate renal impairment. The primary outcome occurred in 6 of 105 patients (5.7%) with normal renal function vs 13 of 59 patients (22.0%) with moderate renal impairment, representing an unadjusted odds ratio of 4.7 (95% CI, 1.7-13.0; P = .002).

That's rather concerning. FDA approved labeling calls for no adjustment until the clearance is below 30 ml/min. So the patients in the reduced renal function group all received the drug “appropriately” according to the approved labeling. Alternatives to address this situation might include the use of unfractionated heparin or enoxaparin dose adjustment based on antiXa monitoring.