Original Research

Enoxaparin vs Continuous Heparin for Periprocedural Bridging in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease

Bridging with enoxaparin rather than heparin has the potential to reduce the length of hospital stay, incidence of nosocomial infections, and cost of hospitalization.

Fed Pract. 2019 July;36(7):306-315

Author(s):

Chandler David Schexnayder, PharmD, BCPS

Christine Aguilar, PharmD, BCPS

Kathleen Morneau, PharmD, BCPS

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References

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3. Hammerstingl C, Schmitz A, Fimmers R, Omran H. Bridging of chronic oral anticoagulation with enoxaparin in patients with atrial fibrillation: results from the prospective BRAVE registry. Cardiovasc Ther. 2009;27(4):230-238.

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There has been a long-standing controversy in the use of parenteral anticoagulation for perioperative bridging in patients with atrial fibrillation (AF) pursuing elective surgery.¹ The decision to bridge is dependent on the patient’s risk of thromboembolic complications and susceptibility to bleed.¹ The BRIDGE trial showed noninferiority in rate of stroke and embolism events between low molecular weight heparins (LMWHs) and no perioperative bridging.² However, according to the American College of Chest Physicians (CHEST) 2012 guidelines, patients in the BRIDGE trial would be deemed low risk for thromboembolic events displayed by a mean CHADS₂ (congestive heart failure [CHF], hypertension, age, diabetes mellitus, and stroke/transient ischemic attack) score of 2.3. Also, the BRIDGE study and many others excluded patients with advanced forms of chronic kidney disease (CKD).^2,3

Similar to patients with AF, patients with advanced CKD (ACKD, stage 4 and 5 CKD) have an increased risk of stroke and venous thromboembolism (VTE).^4,5 Patients with AF and ACKD have not been adequately studied for perioperative anticoagulation bridging outcomes. Although unfractionated heparin (UFH) is preferred over LMWH in ACKD patients,enoxaparin can be used in this population.^1,6 Enoxaparin 1 mg/kg once daily is approved by the US Food and Drug Administration (FDA) for use in patients with severe renal insufficiency defined as creatinine clearance (CrCl) < 30 mL/min. This dosage adjustment is subsequent to studies with enoxaparin 1 mg/kg twice daily that showed a significant increase in major and minor bleeding in severe renal-insufficient patients with CrCl < 30 mL/min vs patients with CrCl > 30 mL/min.⁷ When comparing the myocardial infarction (MI) outcomes of severe renal-insufficient patients in the ExTRACT-TIMI 25 trial, enoxaparin 1 mg/kg once daily had no significant difference in nonfatal major bleeding vs UFH.⁸ In patients without renal impairment (no documentation of kidney disease), bridging therapy with LMWH was completed more than UFH in < 24 hours of hospital stay and with similar rates of VTEs and major bleeding.⁹ In addition to its ability to be administered outpatient, enoxaparin has a more predictable pharmacokinetic profile, allowing for less monitoring and a lower incidence of heparin-induced thrombocytopenia (HIT) vs that of UFH.⁶

The Michael E. DeBakey Veteran Affairs Medical Center (MEDVAMC) in Houston, Texas, is one of the largest US Department of Veterans Affairs (VA) hospitals in the US, managing > 150,000 veterans in Southeast Texas and other southern states. As a referral center for traveling patients, it is crucial that MEDVAMC decrease hospital length of stay (LOS) to increase space for incoming patients. Reducing LOS also reduces costs and may have a correlation with decreasing the incidence of nosocomial infections. Because of its significance to this facility, hospital LOS is an appropriate primary outcome for this study.

To our knowledge, bridging outcomes between LMWH and UFH in patients with AF and ACKD have never been studied. We hypothesized that using enoxaparin instead of heparin for periprocedural management would result in decreased hospital LOS, leading to a lower economic burden and lower incidence of nosocomial infections with no significant differences in major and minor bleeding and thromboembolic complications.¹⁰