Enoxaparin vs Continuous Heparin for Periprocedural Bridging in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease
Methods
This study was a single-center, retrospective chart review of adult patients from January 2008 to September 2017. The review was conducted at MEDVAMC and was approved by the research and development committee and by the Baylor College of Medicine Institutional Review Board. Formal consent was not required.
Included patients were aged ≥ 18 years with diagnoses of AF or atrial flutter and ACKD as recognized by a glomerular filtration rate (eGFR) of < 30 mL/min/1.73 m2 as calculated by use of the Modification of Diet in Renal Disease Study (MDRD) equation.11 Patients must have previously been on warfarin and required temporary interruption of warfarin for an elective procedure. During the interruption of warfarin therapy, a requirement was set for patients to be on periprocedural anticoagulation with subcutaneous (SC) enoxaparin 1 mg/kg daily or continuous IV heparin per MEDVAMC heparin protocol. Patients were excluded if they had experienced major bleeding in the 6 weeks prior to the elective procedure, had current thrombocytopenia (platelet count < 100 × 109/L), or had a history of heparin-induced thrombocytopenia (HIT) or a heparin allergy.
This patient population was identified using TheraDoc Clinical Surveillance Software System (Charlotte, NC), which has prebuilt alert reviews for anticoagulation medications, including enoxaparin and heparin. An alert for patients on enoxaparin with serum creatinine (SCr) > 1.5 mg/dL was used to screen patients who met the inclusion criteria. A second alert identified patients on heparin. The VA Computerized Patient Record System (CPRS) was used to collect patient data.
Economic Analysis
An economic analysis was conducted using data from the VA Managerial Cost Accounting Reports. Data on the national average cost per bed day was used for the purpose of extrapolating this information to multiple VA institutions.12 National average cost per day was determined by dividing the total cost by the number of bed days for the identified treating specialty during the fiscal period of 2018. Average cost per day data included costs for bed day, surgery, radiology services, laboratory tests, pharmacy services, treatment location (ie, intensive care units [ICUs]) and all other costs associated with an inpatient stay. A cost analysis was performed using this average cost per bed day and the mean LOS between enoxaparin and UFH for each treating specialty. The major outcome of the cost analysis was the total cost per average inpatient stay. The national average cost per bed day for each treating specialty was multiplied by the average LOS found for each treating specialty in this study; the sum of all the average costs per inpatient stay for the treating specialties resulted in the total cost per average inpatient stay. Permission to use these data was granted by the Pharmacy and Critical Care Services at MEDVAMC.
Patient Demographics and Characteristics
Data were collected on patient demographics (Table 1). Nosocomial infections, stroke/transient ischemic attack, MI, VTE, major and minor bleeding, and death are defined in Table 2.
The primary outcome of the study was hospital LOS. The study was powered at 90% for α = .05, which gives a required study population of 114 (1:1 enrollment ratio) patients to determine a statistically significant difference in hospital stay. This sample size was calculated using the mean hospital LOS (the primary objective) in the REGIMEN registry for LMWH (4.6 days) and UFH (10.3 days).9 To our knowledge, the incidence of nosocomial infections (a secondary outcome) has not been studied in this patient population; therefore, there was no basis to assess an appropriate sample size to find a difference in this outcome. Furthermore, the goal was to collect as many patients as possible to best assess this variable. Because of an expected high exclusion rate, 504 patients were reviewed to target a sample size of 120 patients. Due to the single-center nature of this review, the secondary outcomes of thromboembolic complications and major and minor bleeding were expected to be underpowered.
The final analysis compared the enoxaparin arm with the UFH arm. Univariate differences between the treatment groups were compared using the Fisher exact test for categorical variables. Demographic data and other continuous variables were analyzed by an unpaired t test to compare means between the 2 arms. Outcomes and characteristics were deemed statistically significant when α (P value) was < .05. All P values reported were 2-tailed with a 95% CI. No statistical analysis was performed for the cost differences (based on LOS per treating specialty) in the 2 treatment arms. Statistical analyses were completed by utilizing GraphPad Software (San Diego, CA).
