Dosing accuracy of direct oral anticoagulants in an academic medical center
BACKGROUND/OBJECTIVE
Direct-acting oral anticoagulants (DOACs) are increasingly used to prevent or treat thromboembolism. We conducted a study to compare how well initial DOAC prescribing for adult inpatients adhered to dosing recommendations approved by the US Food and Drug Administration (FDA).
DESIGN
Retrospective analysis.
SETTING
Single academic medical center, July 1, 2014 to June 30, 2015.
PATIENTS
508 adult inpatients.
MEASUREMENTS
DOAC prescriptions were evaluated to determine whether they met FDA-recommended dosing and administration according to patient age, weight, sex, race, kidney function, diagnoses, and concomitant medications.
RESULTS
DOACs were prescribed in 635 admissions (247 apixaban, 97 dabigatran, 291 rivaroxaban). The indication was atrial fibrillation/flutter in 465 admissions (8% with bioprostheses or valve repair), chronic deep vein thrombosis (DVT) in 67, acute DVT in 32, chronic pulmonary embolism in 23, acute pulmonary embolism in 19, DVT prevention after hip or knee surgery in 19, and non-FDA-approved indications in 10. Sixteen percent of orders for venous thromboembolic disease were for patients with active malignancy. Dosages not concordant with recommendations were prescribed for apixaban in 18% of admissions, for rivaroxaban in 14%, and for dabigatran in 7% (P = 0.04). Lower than recommended dosing was more common than higher than recommended dosing (P < 0.05). Half the deviations were continuations of outpatient dosing. Atrial fibrillation/flutter and post-hip or -knee surgery dosing deviations were more common than venous thromboembolic disease deviations (P < 0.001) but were not related to prescriber specialty.
CONCLUSIONS
DOAC prescribing recommendation deviations that can affect clinical efficacy were identified. Education and point-of-care decision support tools for improving dosing are needed, as are outcome data for patients who receive DOACs at lower than recommended dosing or for off-label indications. Journal of Hospital Medicine 2017;12:544-550. © 2017 Society of Hospital Medicine
© 2017 Society of Hospital Medicine
Direct-acting oral anticoagulants (DOACs) have been introduced into clinical use for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), prevention of venous thrombosis after hip or knee surgery, and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).1-7 Advantages of DOACs over warfarin are often stated as fixed dosing, minor drug and food interactions, wider therapeutic index, and no need for laboratory test monitoring.1,8 Yet, recommended DOAC dosages vary by renal function and therapeutic indications. Dosing recommendations for prevention of stroke in patients with NVAF are based on estimated creatinine clearance (dabigatran, rivaroxaban, edoxaban), age (apixaban), weight (apixaban, edoxaban), serum creatinine level (apixaban, edoxaban), and presence of cirrhosis by Child-Pugh class9,10 (apixaban, edoxaban).4-6,11,12 Dosing recommendations based on coadministration of strong CYP34A and P-glycoprotein inhibitors or inducers vary by DOAC. In addition, dabigatran cannot be crushed and must be stored in its original packaging, and rivaroxaban should be taken with food when the dose is over 10 mg.
We studied DOAC prescribing in adults admitted to a large academic medical center by comparing initial prescribed dosing with FDA-approved prescribing information. We hypothesized that the complexity of DOAC dosing may not be recognized by prescribers.
METHODS
Our study protocol was approved by the Committee on Human Research (Institutional Review Board) of the University of California San Francisco.
Data Collection
We used electronic medical records (EMRs) to identify adult inpatients who were prescribed a DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) at the University of California San Francisco Medical Center, a large academic hospital, between July 1, 2014 and June 30, 2015. Demographic and medical information related to therapeutic indications, contraindications, and indications for dose adjustments were collected and included diagnoses classified by International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) for venous thromboses; phlebitis or thrombophlebitis; PE or venous embolism; atrial arrhythmias; surgical procedures; cirrhosis and/or ascites or liver disease; coagulopathies; artificial heart valves or implanted devices; prior use of medications including parenteral anticoagulants; and laboratory data obtained before the first DOAC order (serum creatinine level, estimated glomerular filtration rate [eGFR] determined by Chronic Kidney Disease Epidemiology Collaboration,13 international normalized ratio, or, if available, activated partial thromboplastin time and bilirubin level). Creatinine clearance was calculated with the Cockcroft-Gault method14 using total body weight, per drug label recommendation. Child-Pugh class was calculated if cirrhosis was diagnosed.10 DOAC dose, frequency, dosing directions, and prescriber medical specialty were determined.
