Enoxaparin Outcomes in Patients With Moderate Renal Impairment

Abstract

Background: Enoxaparin sodium has predictable pharmacokinetics that allow for simplified dosing without laboratory monitoring. Reliance on renal function for excretion may lead to accumulation of enoxaparin in patients with moderate renal impairment. However, there is no dose adjustment recommended for these patients. We conducted a review to compare bleeding events in patients with moderate renal impairment compared with those with normal renal function.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). The odds ratio using multivariable logistic regression adjusting for differences in risk was 3.9 (95% CI, 0.97-15.6; P=.055). There was no recurrent thromboembolism in either group. Conclusions:Our results suggest an increased risk of major bleeding in patients with moderate renal impairment who receive enoxaparin. Because enoxaparin is frequently used and outcomes can be life saving or life threatening, we encourage further study of the appropriate dose in patients with moderate renal impairment.

Clinical Outcomes and Adherence to Guideline Recommendations During the Initial Treatment of Acute Venous Thromboembolism

“…Another study in 164 patients treated with enoxaparin reported a 5.7% incidence of major bleeding within 14 days of completing enoxaparin therapy in patients with CrCl ≥80 mL/min as compared with a 22.0% incidence in patients with a CrCl between 30 and 50 mL/min (P = 0.002). 15 Notably, this population differed from ours, in that 62% of patients were chronic warfarin users receiving parenteral anticoagulants for bridge therapy, and only 27% of patients were treated for acute VTE. The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively).…”

“…The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively). 15 The lower bleeding rate in our study suggests that adjusting parenteral anticoagulant therapy based on renal function (enoxaparin 1 mg/kg once daily or unfractionated heparin) may be associated with a lower risk of major bleeding without increasing the risk of recurrent VTE.…”

Clinical Outcomes and Adherence to Guideline Recommendations During the Initial Treatment of Acute Venous Thromboembolism

“…Another study in 164 patients treated with enoxaparin reported a 5.7% incidence of major bleeding within 14 days of completing enoxaparin therapy in patients with CrCl ≥80 mL/min as compared with a 22.0% incidence in patients with a CrCl between 30 and 50 mL/min (P = 0.002). 15 Notably, this population differed from ours, in that 62% of patients were chronic warfarin users receiving parenteral anticoagulants for bridge therapy, and only 27% of patients were treated for acute VTE. The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively).…”

“…The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively). 15 The lower bleeding rate in our study suggests that adjusting parenteral anticoagulant therapy based on renal function (enoxaparin 1 mg/kg once daily or unfractionated heparin) may be associated with a lower risk of major bleeding without increasing the risk of recurrent VTE.…”

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

“…14 DeCarolis et al reported a greater incidence of major bleeding in those with renal impairment who received therapeutic enoxaparin compared to healthy volunteers who received the same drug. 15 Chow et al also found a tight linear relationship between creatinine clearance and antiXa concentrations with enoxaparin. 16 In contrast, TrujilloSantos et al showed no difference in fatal bleeding between the two groups and reported a twofold mortality increase in the group receiving UFH versus those receiving any LMWH with CrCl less than 30 mL/min.…”

Risk Factors for Bleeding Events with Enoxaparin, Dabigatran and Fondaparinux in Hospitalized Patients with Varying Levels of Renal Impairment

“…Interestingly, patients presenting with bleeding episodes with moderate renal impairment were more likely to be female (78%) and greater than 75 years of age. While advanced age was previously recognized as a potential risk factor, gender has not been implicated [22]. Of note, the mean BMI for all enoxaparin patients was 31.7, classifying these patients as obese.…”

Clinical Outcomes and Adherence to Guideline Recommendations During the Initial Treatment of Acute Venous Thromboembolism

“…Another study in 164 patients treated with enoxaparin reported a 5.7% incidence of major bleeding within 14 days of completing enoxaparin therapy in patients with CrCl ≥80 mL/min as compared with a 22.0% incidence in patients with a CrCl between 30 and 50 mL/min (P = 0.002). 15 Notably, this population differed from ours, in that 62% of patients were chronic warfarin users receiving parenteral anticoagulants for bridge therapy, and only 27% of patients were treated for acute VTE. The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively).…”

“…The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively). 15 The lower bleeding rate in our study suggests that adjusting parenteral anticoagulant therapy based on renal function (enoxaparin 1 mg/kg once daily or unfractionated heparin) may be associated with a lower risk of major bleeding without increasing the risk of recurrent VTE.…”

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

“…14 DeCarolis et al reported a greater incidence of major bleeding in those with renal impairment who received therapeutic enoxaparin compared to healthy volunteers who received the same drug. 15 Chow et al also found a tight linear relationship between creatinine clearance and antiXa concentrations with enoxaparin. 16 In contrast, TrujilloSantos et al showed no difference in fatal bleeding between the two groups and reported a twofold mortality increase in the group receiving UFH versus those receiving any LMWH with CrCl less than 30 mL/min.…”

Risk Factors for Bleeding Events with Enoxaparin, Dabigatran and Fondaparinux in Hospitalized Patients with Varying Levels of Renal Impairment

“…Interestingly, patients presenting with bleeding episodes with moderate renal impairment were more likely to be female (78%) and greater than 75 years of age. While advanced age was previously recognized as a potential risk factor, gender has not been implicated [22]. Of note, the mean BMI for all enoxaparin patients was 31.7, classifying these patients as obese.…”

Clinical Outcomes and Adherence to Guideline Recommendations During the Initial Treatment of Acute Venous Thromboembolism

“…Another study in 164 patients treated with enoxaparin reported a 5.7% incidence of major bleeding within 14 days of completing enoxaparin therapy in patients with CrCl ≥80 mL/min as compared with a 22.0% incidence in patients with a CrCl between 30 and 50 mL/min (P = 0.002). 15 Notably, this population differed from ours, in that 62% of patients were chronic warfarin users receiving parenteral anticoagulants for bridge therapy, and only 27% of patients were treated for acute VTE. The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively).…”

“…The subset of patients who had newly initiated anticoagulation therapy had lower major bleeding rates compared with chronic warfarin users (8.1% vs 13.7%, respectively). 15 The lower bleeding rate in our study suggests that adjusting parenteral anticoagulant therapy based on renal function (enoxaparin 1 mg/kg once daily or unfractionated heparin) may be associated with a lower risk of major bleeding without increasing the risk of recurrent VTE.…”

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

“…14 DeCarolis et al reported a greater incidence of major bleeding in those with renal impairment who received therapeutic enoxaparin compared to healthy volunteers who received the same drug. 15 Chow et al also found a tight linear relationship between creatinine clearance and antiXa concentrations with enoxaparin. 16 In contrast, TrujilloSantos et al showed no difference in fatal bleeding between the two groups and reported a twofold mortality increase in the group receiving UFH versus those receiving any LMWH with CrCl less than 30 mL/min.…”

Risk Factors for Bleeding Events with Enoxaparin, Dabigatran and Fondaparinux in Hospitalized Patients with Varying Levels of Renal Impairment

“…Interestingly, patients presenting with bleeding episodes with moderate renal impairment were more likely to be female (78%) and greater than 75 years of age. While advanced age was previously recognized as a potential risk factor, gender has not been implicated [22]. Of note, the mean BMI for all enoxaparin patients was 31.7, classifying these patients as obese.…”