Characteristics and Outcomes in Patients with Venous Thromboembolism Taking Concomitant Anti-Platelet Agents and Anticoagulants in the AMPLIFY TrialFunding 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.
15 February 2018
21 November 2018
16 January 2019 (eFirst)
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.
Keywordsanti-platelet agents - venous thrombosis - clinical trials: oral anticoagulants - deep vein thrombosis - pulmonary embolism
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.
- 1 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
- 2 Prandoni P. Venous and arterial thrombosis: two aspects of the same disease?. Clin Epidemiol 2009; 1: 1-6
- 3 Prandoni P, Bilora F, Marchiori A. , et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348 (15) 1435-1441
- 4 Green D. Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism. Hematology (Am Soc Hematol Educ Program) 2009; 2009: 259-266
- 5 Cohen AT, Gitt AK, Bauersachs R. , et al. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry. Thromb Haemost 2017; 117 (07) 1326-1337
- 6 Klok FA, Hösel V, Clemens A. , et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J 2016; 48 (05) 1369-1376
- 7 Davidson BL, Verheijen S, Lensing AW. , et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014; 174 (06) 947-953
- 8 Alexander JH, Lopes RD, Thomas L. , et al. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2014; 35 (04) 224-232
- 9 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
- 10 Douketis JD. Combination warfarin-ASA therapy: which patients should receive it, which patients should not, and why?. Thromb Res 2011; 127 (06) 513-517