Kirsten K Viktil1,2, Ina Lehre1,2, Anette H Ranhoff3,4, Espen Molden5,6. 1. Diakonhjemmet Hospital Pharmacy, Oslo, Norway. 2. School of Pharmacy, University of Oslo, Oslo, Norway. 3. Departments of Medicine and Surgery, Diakonhjemmet Hospital, Oslo, Norway. 4. Department of Clinical Science, University of Bergen, Bergen, Norway. 5. School of Pharmacy, University of Oslo, Oslo, Norway. espen.molden@farmasi.uio.no. 6. Therapeutic Drug Monitoring Unit, Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 23, Vinderen, 0319, Oslo, Norway. espen.molden@farmasi.uio.no.
Abstract
BACKGROUND: Use of direct-acting oral anticoagulants (DOACs) is increasing, but knowledge about pharmacokinetics and safety in frail patients is lacking. OBJECTIVE: The aim was to determine serum concentrations and elimination rates of DOACs in older hip fracture patients hospitalized for surgery. METHODS: The study included patients ≥ 65 years of age hospitalized for acute hip fracture surgery over a period of 6 months. Use of antithrombotic drugs was registered and serum samples collected for analysis of DOACs (apixaban, dabigatran and rivaroxaban) at admission and surgery. Measured concentrations were assessed in relation to reference (therapeutic) ranges of the respective drugs and applied for half-life calculations. Furthermore, waiting time for surgery was compared between DOAC and warfarin users. RESULTS: Of 167 patients included (median age 84 years), 11 and 14 used DOACs and warfarin, respectively. Seven of the DOAC-treated patients had concentrations above the upper reference range (> 300 nM) at admission, and concentrations were still in the reference range for five of these at surgery. Elimination half-lives could be estimated in eight patients and ranged between 14.6 and 59.7 h (median 21.6). The observed waiting time for surgery was longer for patients using DOACs than warfarin (median 44 vs. 25 h). CONCLUSION: This pilot study indicates that older patients prone to hip fracture are at risk of being exposed to therapeutic serum concentrations of DOACs during surgery due to reduced drug elimination rates. The observation that almost 50% of the patients had therapeutic concentrations at surgery should be investigated further regarding safety of DOAC use in this frail elderly population.
BACKGROUND: Use of direct-acting oral anticoagulants (DOACs) is increasing, but knowledge about pharmacokinetics and safety in frail patients is lacking. OBJECTIVE: The aim was to determine serum concentrations and elimination rates of DOACs in older hip fracturepatients hospitalized for surgery. METHODS: The study included patients ≥ 65 years of age hospitalized for acute hip fracture surgery over a period of 6 months. Use of antithrombotic drugs was registered and serum samples collected for analysis of DOACs (apixaban, dabigatran and rivaroxaban) at admission and surgery. Measured concentrations were assessed in relation to reference (therapeutic) ranges of the respective drugs and applied for half-life calculations. Furthermore, waiting time for surgery was compared between DOAC and warfarin users. RESULTS: Of 167 patients included (median age 84 years), 11 and 14 used DOACs and warfarin, respectively. Seven of the DOAC-treated patients had concentrations above the upper reference range (> 300 nM) at admission, and concentrations were still in the reference range for five of these at surgery. Elimination half-lives could be estimated in eight patients and ranged between 14.6 and 59.7 h (median 21.6). The observed waiting time for surgery was longer for patients using DOACs than warfarin (median 44 vs. 25 h). CONCLUSION: This pilot study indicates that older patients prone to hip fracture are at risk of being exposed to therapeutic serum concentrations of DOACs during surgery due to reduced drug elimination rates. The observation that almost 50% of the patients had therapeutic concentrations at surgery should be investigated further regarding safety of DOAC use in this frail elderly population.
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