Hospital admissions for bleeding events associated with treatment with apixaban, dabigatran and rivaroxaban

Abstract

ObjectivesTo analyse the hospital admissions for bleeding events associated with treatment with direct oral anticoagulants (DOACs). To describe the characteristics and outcomes of those patients.MethodsA retrospective observational study was carried out in the framework of an integral risk management plan of drugs and proactive pharmacovigilance of hospital admissions for bleeding associated with apixaban, dabigatran and rivaroxaban from April 2015 through December 2016. Cases were identified using the information management tool of Orion Clinic (hospital electronic medical history) and by reviewing the hospital discharge reports. Various biometric, clinical and pharmacotherapeutic variables of each patient were registered.Results37 hospitalisation episodes for DOAC-induced bleeding in 32 patients (15 received rivaroxaban, 9 apixaban and 8 dabigatran) were detected, representing an incidence rate of 3.44 per 100 person-years (95% CI 2.35 to 4.86). The most common bleeding site was gastrointestinal (27 cases, 73.0%). Intracranial bleeding was rare (three cases, 8.1%). Four patients (12.5%) were receiving DOACs at full doses and had a ’dose reduction indication'. The mean (SD) length of stay was 8.4 (5.2) days. Three patients (8.1%) died during the hospitalisation. Among bleeding episodes without fatal outcome, DOACs were stopped in 14 cases, continued in 14 cases, switched for another DOAC in two cases and the dose was reduced in four cases.ConclusionsDOACs are associated with serious bleeding events that require hospitalisation. The risk/benefit ratio assessment considering patient preferences and an individualised follow-up, especially in patients who are elderly, polymedicated or have impaired renal function, can help to reinforce the safe use of DOACs.

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

“…2,9 Bleeding disorders are one of the most common causes of ADR-related hospitalizations. [10][11][12] Drug-induced bleeding disorders contribute to substantial morbidity, mortality, and cost to society. 13,14 Antithrombotic agents are the common drugs that cause unintended bleeding.…”

Elderly people are inherently sensitive to the pharmacological activity of rivaroxaban: implications for DOAC prescribing

“…The incidence rate of hospitalization for DOAC-related bleeding has been reported as 3.44 per 100 patient-years (95% CI 2.35–4.86) with 87% of the admissions being aged ≥75 years, reflecting both the age profile of those prescribed these drugs and their increased risk of bleeding due to age, renal insufficiency, comorbidities and concomitant medication. Of these patients, 19% were receiving the maximum therapeutic daily doses in spite of dose reduction recommendations [ 19 ]. Elderly people were not well represented in the major clinical trials evaluating the safety and efficacy of DOACs and this is of concern for clinicians prescribing these agents.…”

ROTEM Testing for Direct Oral Anticoagulants

“…Generally, the safety profile of these agents appears to be comparable to or even more favorable than VKA [10][11][12][13] ; however, anticoagulants of all types, including DOACs, can induce or contribute to bleeding. Marco Garbayo et al 14 recently reported an incidence rate of 3.44 per 100 person-years for hospitalizations for DOACs-associated bleeding in their retrospective observational study. The most common bleeding was gastrointestinal bleeding (73.0%), from which 8.1% of patients died during hospitalization.…”