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Thromb Haemost 2016; 115(04): 809-816
DOI: 10.1160/TH15-09-0752
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Early time courses of recurrent thromboembolism and bleeding during apixaban or enoxaparin/warfarin therapy

A sub-analysis of the AMPLIFY trial
Gary E. Raskob
1   College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
,
Alex S. Gallus
2   Department of Haematology, SA Pathology at Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia
,
Paul Sanders
3   Pfizer Ltd., Walton Oaks, Walton on the Hill, Tadworth, Surrey, UK
,
John R. Thompson
4   Pfizer Inc., Groton, Conneticut, USA
,
Giancarlo Agnelli
5   Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy
,
Harry R. Buller
6   Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands
,
Alexander T. Cohen
7   Department of Haematological Medicine, Guys and St. Thomas Hospital, London, UK
,
Eduardo Ramacciotti
8   Vascular Surgery, Hospital Israelita Albert Einstein, Säo Paulo, Brazil
,
Jeffrey I. Weitz
9   Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
› Author Affiliations Financial support: This study was funded by Pfizer Inc. and Bristol-Myers Squibb Company.
Further Information

Publication History

Received: 24 September 2015

Accepted after minor revision: 13 November 2015

Publication Date:
11 November 2017 (online)

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Summary

Risks of recurrence and bleeding are highest during the first weeks of anticoagulant therapy for venous thromboembolism (VTE). We therefore examined the early time course of recurrence and major bleeding in a pre-specified sub-analysis of the AMPLIFY trial, a randomised, double-blind, six-month comparison of oral apixaban with conventional therapy (enoxaparin followed by warfarin) in 5,395 patients with symptomatic proximal deep-vein thrombosis or pulmonary embolism. Early events were of particular interest because apixaban was given without initial heparin treatment. The primary efficacy and safety outcomes were the incidences of the adjudicated composite of recurrent symptomatic VTE or death related to VTE, and of adjudicated major bleeding, respectively. This analysis reports on recurrence and bleeding after 7, 21, and 90 days of therapy, in addition to the previously reported end-of-study results. These were the times specified before statistical analysis. Recurrent VTE after 7, 21, and 90 days, and six months had occurred in 18 (0.7%), 29 (1.1%), 46 (1.8%), and 59 patients (2.3%), respectively, given apixaban, and in 23 (0.9%), 35 (1.3%), 58 (2.2%), and 71 patients (2.7%), respectively, given conventional therapy. Major bleeding had occurred during these time intervals in 3 (0.1%), 5 (0.2%), 11 (0.4%), and 15 patients (0.6%), respectively, who received apixaban, and in 16 (0.6%), 26 (1.0%), 38 (1.4%), and 49 patients (1.8%), respectively, given conventional therapy. Efficacy of apixaban was non-inferior at each time point, with no excess of early recurrences. The reduced bleeding risk associated with apixaban began early during the course of treatment.

Keywords

Venous thrombosis - pulmonary embolism - anticoagulant therapy
 

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