Association of Bleeding Events with the Administration of Doac Following >36 Hours of Inpatient Anticoagulation

For patients diagnosed with venous thromboembolisms (VTE) in the form of Deep Vein Thromboses (DVT) or Pulmonary Embolisms (PE) while in the hospital, intravenous unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are most commonly used as anticoagulation treatment. In the outpatient setting, patients who are able to tolerate oral anticoagulation are most commonly given apixaban or rivaroxaban, Factor Xa inhibitors that decrease clot strength and generation, and require a higher dose upon initiation followed by a smaller maintenance dose for the length of treatment time, usually 3-6 months.

In 2014, G. Agnelli et al. studied the efficacy of apixaban for anticoagulation compared to the standard therapy of enoxaparin dosed concurrently with warfarin until the international normalized ratio (INR) reached 2.0-3.0. The primary efficacy outcome compared recurrence of VTE or PE or death due to thromboembolism in either the apixaban or standard regimen, and the secondary outcome was concerned with recurrence or death due to thromboembolism, plus death from all other causes. In the results, apixaban was non-inferior to warfarin in terms of efficacy and also showed a 69% reduction in major bleeding events. However, the exclusion criteria included those that received two doses LMWH dosed daily, or more than three doses of a LMWH dosed daily, or continuous infusion of unfractionated heparin for more than 36 hours before the first administration of apixaban. In the hospital setting, many patients are placed on LMWH or UFH for more than the exclusion criteria range would allow, and are subsequently discharged on oral anticoagulation such as apixaban or rivaroxaban to finish a 3-6 month

treatment regimen.

In this regional retrospective study encompassing 8 hospitals between 1/1/2017 - 12/31/2023, data was retrieved on the amount of bleeding events, return ER visits or readmissions, and deaths after initial admission where VTE was diagnosed and >36 hours of UFH or LMWH given. The number of events occurring after initial admit was compared between patients who received apixaban or rivaroxaban on discharge with the higher initial dose on discharge than patients who did not receive the higher initial dose. Patients included in the study were 18 years or older who were diagnosed with a DVT and/or PE while inpatient and received ≥36 hours of IV anticoagulation with UFH or LMWH, then were prescribed oral anticoagulation with apixaban or rivaroxaban for treatment after discharge. Those who were excluded had apixaban or rivaroxaban on their medication reconciliation, or did not receive a VTE diagnosis while inpatient. We controlled for other variables such as demographics, alcohol use, and renal failure. The results of this study can help standardize prescribing practices by providing data on the safety of prescribing oral anticoagulation after >36 hours of anticoagulation inpatient. 3209 total patients were included, and of these, 1107 were readmitted or returned to the ER within 60 days. Of the 1107 patients, 78 patients had officially been diagnosed with bleeding events, 166

required transfusions, 491 were readmitted with VTE, and 76 patients expired. It was noted that of the 166 patients who received a transfusion, only 29 received the full initial dose of DOAC. The likelihood of having a bleeding event, receiving a transfusion, having an additional VTE diagnosis, or death was not significantly associated in those receiving the full loading dose of DOAC versus those who did not after the 36 hours of inpatient anticoagulation. However, when completing this study there were limitations. Most notable was that patients may have sought care at a facility other than where the initial VTE was diagnosed, and would go unaccounted for, or patients may not have had bleeding events significant enough to warrant an ER visit. Our data suggests prescribing the higher initial dose of apixaban or rivaroxaban after receiving 36 hours of therapeutic LMWH or continuous UFH in addition to the lower maintenance dose does not lead to an increase in bleeding events with or without transfusions, readmissions, new clot diagnoses, or death.

No relevant conflicts of interest to declare.