Apixaban Reduces Hospitalizations in Patients With Venous Thromboembolism: An Analysis of the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) Trial

Xianchen Liu, Margot Johnson, Jack Mardekian, Hemant Phatak, John Thompson, Alexander T Cohen, Xianchen Liu, Margot Johnson, Jack Mardekian, Hemant Phatak, John Thompson, Alexander T Cohen

Abstract

Background: In the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial, apixaban was noninferior to enoxaparin/warfarin in preventing recurrent symptomatic venous thromboembolism (VTE) or venous thromboembolism-related death, with significantly less bleeding. This analysis evaluated the effects of apixaban versus enoxaparin/warfarin on all-cause hospitalizations during AMPLIFY.

Methods and results: Of the 5365 patients included, 2676 received apixaban and 2689 received enoxaparin/warfarin. All-cause hospitalizations during the treatment period after the index event were captured using dedicated case report forms. Outcomes included all-cause hospitalizations and time from randomization to first hospitalization. Patients were censored at death, loss to follow-up, or end of study, whichever came first. Treatment effects were assessed using Cox proportional hazards regression models. During the treatment period after the index event, 343 patients were hospitalized at least once: 153 (5.72%) in the apixaban group and 190 (7.07%) in the enoxaparin/warfarin group. Compared with enoxaparin/warfarin, apixaban significantly reduced all-cause hospitalizations (hazard ratio 0.804, 95% CI=0.650-0.995, P=0.045). All-cause hospitalization rates within the first 30 days after the index event were 2.28% and 3.35% in the apixaban and enoxaparin/warfarin groups, respectively (hazard ratio 0.676, 95% CI=0.488-0.935, P=0.018). For all patients, the average per-patient estimated mean length of hospital stay was also shorter with apixaban than enoxaparin/warfarin (0.57 days versus 1.01 days, P<0.0001).

Conclusions: Apixaban significantly reduced all-cause hospitalizations versus enoxaparin/warfarin, and shortened the length of hospital stay in patients with acute venous thromboembolism.

Clinical trial registration: URL: https://Clinicaltrials.Gov/. Unique identifier: NCT00643201.

Keywords: anticoagulants; hemorrhage; mortality; prevention; thrombosis.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Time to first hospitalization by treatment group (A) during the trial after an index event and (B) during the first 30 days after an index event.
Figure 2
Figure 2
Comparison of the treatment effect of apixaban vs warfarin for time to first hospitalization in key subgroups. DVT indicates deep‐vein thrombosis; PE, pulmonary embolism.

References

    1. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama MM, Spannagl M; VTE Impact Assessment Group in Europe (VITAE) . Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756–764.
    1. Goldhaber SZ. Preventing pulmonary embolism and deep vein thrombosis: a ‘call to action’ for vascular medicine specialists. J Thromb Haemost. 2007;5:1607–1609.
    1. Heit J, Cohen A, Anderson FJ. Estimated annual number of incident and recurrent, non‐fatal and fatal venous thromboembolism (VTE) events in the US. Blood (ASH Annual Meeting Abstracts). 2005;106:Abstract 910.
    1. Lloyd‐Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, de Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, Wasserthiel‐Smoller S, Wong ND, Wylie‐Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Heart disease and stroke statistics‐2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215.
    1. Nieto JA, Camara T, Gonzalez‐Higueras E, Ruiz‐Gimenez N, Guijarro R, Marchena PJ, Monreal M; RIETE Investigators . Clinical outcome of patients with major bleeding after venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost. 2008;100:789–796.
    1. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141:e44S–e88S.
    1. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR; American College of Chest Physicians . Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141:e419S–e494S.
    1. Van EJ, Eerenberg ES, Kamphuisen PW, Buller HR. How to prevent, treat, and overcome current clinical challenges of VTE. J Thromb Haemost. 2011;9(suppl 1):265–274.
    1. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–198S.
    1. Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda‐Garcia R, Reeves RA, LaCreta F. Apixaban, an oral, direct factor Xa inhibitor: single‐dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol. 2013;75:476–487.
    1. Frost C, Nepal S, Wang J, Schuster A, Byon W, Boyd RA, Yu Z, Shenker A, Barrett YC, Mosqueda‐Garcia R, Lacreta F. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol. 2013;76:776–786.
    1. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators . Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799–808.
    1. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY‐EXT Investigators . Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699–708.
    1. Liu X, Thompson J, Phatak H, Mardekian J, Porcari AR, Johnson M. Apixaban reduces hospitalization in patients with venous thromboembolism: an analysis of the AMPLIFY‐EXT trial. Thromb Haemost. 2015 Oct 8;115(1). [Epub ahead of print].
    1. Clafin AB, Mitchell CR, Liu X, Phatak H, Mitchell SA. Economic burden of venous thromboembolism across patient populations: a literature review. Presentation at ISPOR Annual European Congress 2013; Dublin, Ireland.
    1. Khorana AA, Dalal MR, Lin J, Connolly GC. Health care costs associated with venous thromboembolism in selected high‐risk ambulatory patients with solid tumors undergoing chemotherapy in the United States. Clinicoecon Outcomes Res. 2013;5:101–108.
    1. van den Belt AG, Bossuyt PM, Prins MH, Gallus AS, Buller HR. Replacing inpatient care by outpatient care in the treatment of deep venous thrombosis–an economic evaluation. TASMAN Study Group. Thromb Haemost. 1998;79:259–263.
    1. Lanitis T, Leipold R, Hamilton M, Rublee D, Quon P, Browne C, Cohen A. Cost‐effectiveness of apixaban compared to other anticoagulants for the acute (6‐month) treatment of venous thromboembolism. Eur Heart J. 2014;35(abstract suppl):1064.
    1. Aujesky D, Stone RA, Kim S, Crick EJ, Fine MJ. Length of hospital stay and post discharge mortality in patients with pulmonary embolism: a statewide perspective. Arch Intern Med. 2008;168:706–712.

Source: PubMed

3
Předplatit