CC BY-NC-ND 4.0 · Thromb Haemost 2019; 119(03): 461-466
DOI: 10.1055/s-0038-1676983
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Characteristics and Outcomes in Patients with Venous Thromboembolism Taking Concomitant Anti-Platelet Agents and Anticoagulants in the AMPLIFY Trial

Alexander T. Cohen
1  Department of Haematology, Guy’s and St Thomas' Hospitals, King's College London, London, United Kingdom
,
Giancarlo Agnelli
2  Internal, Vascular and Emergency Medicine, University of Perugia, Perugia, Italy
,
Harry R. Buller
3  Department of Vascular Medicine, Academic Medical Center, Universiteit van Amsterdam, Amsterdam, The Netherlands
,
Alexander Gallus
4  Department of Haematology, Flinders Medical Centre, Flinders University, Adelaide, Australia
,
Gary E. Raskob
5  Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, University of Oklahoma, Oklahoma, United States
,
Paul Sanders
6  Pfizer Ltd, Walton Oaks, Walton on the Hill, Tadworth, Surrey, United Kingdom
,
John Thompson
7  Pfizer Inc, Groton, Connecticut, United States
,
Jeffrey I. Weitz
8  McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
› Author Affiliations
Funding Pfizer and Bristol-Myers Squibb sponsored the AMPLIFY study and the analysis reported here. The steering committee, consisting of academic authors and authors who are employees of Pfizer, had final responsibility for the study design, oversight and data verification and analyses. The sponsors collected and maintained the data. All authors had full access to the data at all times and interpreted the data.
Further Information

Publication History

15 February 2018

21 November 2018

Publication Date:
16 January 2019 (eFirst)

Abstract

The double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0–3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676; enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%]; enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58–2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52–1.13); interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11–0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15–0.63); interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.

Authors' Contributions

A.T.C., G.A., H.R.B., A.G., G.E.R. and J.I.W. designed the study, and analysed and interpreted the data. P.S. and J.T. analysed and interpreted the data. All authors had full access to the data. A.T.C. prepared the first draft of the manuscript, and all authors revised it critically for important intellectual content. All authors gave their consent to the final version of the manuscript.


Supplementary Material