title: Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin. Results from the AMPLIFY trial.
abstract: Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using pre-designed classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5 % of apixaban versus 44.9 % of enoxaparin/warfarin related recipients (OR 0.49, 95 % confidence interval [CI] 0.14-1.78). A severe clinical course was observed in 14.3 % and in 12.2 %, respectively (OR 1.19, 95 %CI 0.21-6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25 % of apixaban recipients compared to 22.7 % in the enoxaparin/warfarin group (OR 1.13, 95 %CI 0.65-1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.
authors: Suzanne M. Bleker, Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands, Tel.: +31 20 5668274, Fax: +31 20 5669434, E-mail: s.m.bleker@amc.uva.nl.
authors: Suzanne M
authors: SM
authors: Bleker
authors: Alexander T
authors: AT
authors: Cohen
authors: Harry R
authors: HR
authors: Büller
authors: Giancarlo
authors: G
authors: Agnelli
authors: Alexander S
authors: AS
authors: Gallus
authors: Gary E
authors: GE
authors: Raskob
authors: Jeffrey I
authors: JI
authors: Weitz
authors: Madelyn
authors: M
authors: Curto
authors: Melanie
authors: M
authors: Sisson
authors: Saskia
authors: S
authors: Middeldorp
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D017984:Enoxaparin / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000145:classification; D006801:Humans; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D011728:Pyridones / Q000009:adverse effects* / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000150:complications* / Q000188:drug therapy; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: Anticoagulants; apixaban; coumarins; haemorrhage; venous thromboembolism