Download PDF
CC BY-NC-ND 4.0 · Thromb Haemost 2018; 118(11): 1951-1961
DOI: 10.1055/s-0038-1673689
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice

Derek Weycker
1   Policy Analysis Inc. (PAI), Brookline, Massachusetts, United States
,
Xiaoyan Li
2   Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Gail DeVecchis Wygant
2   Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Theodore Lee
3   Pfizer Inc., New York, New York, United States
,
Melissa Hamilton
2   Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Xuemei Luo
4   Pfizer Inc., Groton, Connecticut, United States
,
Lien Vo
2   Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Jack Mardekian
3   Pfizer Inc., New York, New York, United States
,
Xianying Pan
5   Bristol-Myers Squibb, Wallingford, Connecticut, United States
,
Leah Burns
2   Bristol-Myers Squibb, Lawrenceville, New Jersey, United States
,
Mark Atwood
1   Policy Analysis Inc. (PAI), Brookline, Massachusetts, United States
,
Ahuva Hanau
1   Policy Analysis Inc. (PAI), Brookline, Massachusetts, United States
,
Alexander T. Cohen
6   Guy's and St. Thomas' Hospitals, London, United Kingdom
› Author Affiliations Funding Funding for this research was provided to Policy Analysis Inc. (PAI) by Bristol-Myers Squibb (BMS) and Pfizer Inc.
Further Information

Publication History

04 June 2018

29 August 2018

Publication Date:
24 October 2018 (online)

Also available at
   Permissions and Reprints

Corrected by:

Erratum: Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical PracticeThromb Haemost 2018; 118(11): e1-e2
DOI: 10.1055/s-0039-3400530

Abstract

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64–0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71–0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70–0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

Keywords

apixaban - warfarin - venous thromboembolism - bleeding

Note

Some aspects of this research were presented at the American College of Cardiology's 67th Annual Scientific Session (March 2018) in Orlando, Florida.


Supplementary Material

 

  • References

  • 1 Coleman CI, Baugh C, Crivera C. , et al. Healthcare costs associated with rivaroxaban or warfarin use for the treatment of venous thromboembolism. J Med Econ 2017; 20 (02) 200-203
    CrossrefPubMedGoogle Scholar
  • 2 Pendergraft T, Liu X, Edelsberg J. , et al. Prophylaxis against venous thromboembolism in hospitalized medically ill patients. Circ Cardiovasc Qual Outcomes 2013; 6 (01) 75-82
    CrossrefPubMedGoogle Scholar
  • 3 Edelsberg J, Hagiwara M, Taneja C, Oster G. Risk of venous thromboembolism among hospitalized medically ill patients. Am J Health Syst Pharm 2006; 63 (20) (Suppl. 06) S16-S22
    CrossrefPubMedGoogle Scholar
  • 4 Oster G, Ollendorf DA, Vera-Llonch M, Hagiwara M, Berger A, Edelsberg J. Economic consequences of venous thromboembolism following major orthopedic surgery. Ann Pharmacother 2004; 38 (03) 377-382
    CrossrefPubMedGoogle Scholar
  • 5 Anderson Jr FA, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I9-I16
    PubMedGoogle Scholar
  • 6 Cohen AT, Alikhan R, Arcelus JI. , et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94 (04) 750-759
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Heit JA, O'Fallon WM, Petterson TM. , et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162 (11) 1245-1248
    CrossrefPubMedGoogle Scholar
  • 8 Spencer FA, Lessard D, Emery C, Reed G, Goldberg RJ. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007; 167 (14) 1471-1475
    CrossrefPubMedGoogle Scholar
  • 9 Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med 2010; 38 (4, Suppl): S495-S501
    CrossrefPubMedGoogle Scholar
  • 10 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guidelines and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedGoogle Scholar
  • 11 Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017. Available at: http://packageinserts.bms.com/pi/pi_eliquis.pdf . Accessed August 8, 2017
    PubMedGoogle Scholar
  • 12 Pradaxa [package insert]. Ridgefield, CT: Boehringer-Ingelheim Pharmaceuticals Inc.; 2017. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf . Accessed August 8, 2017
    PubMedGoogle Scholar
  • 13 Savaysa [package insert]. Tokyo, Japan: Daiichi Sankyo Inc; 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf . Accessed August 8, 2017
    PubMedGoogle Scholar
  • 14 Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2017. Available at: https://www.xareltohcp.com/shared/product/xarelto/prescribing-information.pdf . Accessed August 8, 2017
    PubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
    CrossrefPubMedGoogle Scholar
  • 17 Büller HR, Prins MH, Lensin AW. , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
    CrossrefPubMedGoogle Scholar
  • 18 Schulman S, Kearon C, Kakkar AK. , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
    CrossrefPubMedGoogle Scholar
  • 19 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
    CrossrefPubMedGoogle Scholar
  • 20 Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017 . Available at: https://packageinserts.bms.com/pi/pi_coumadin.pdf . Accessed August 8, 2017
    PubMed
  • 21 Kearon C, Akl EA, Comerota AJ. , et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9thed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e419S-e496S
    CrossrefPubMedGoogle Scholar
  • 22 Lee LH. DOACs - advances and limitations in real world. Thromb J 2016; 14 (Suppl. 01) 17
    CrossrefPubMedGoogle Scholar
  • 23 Merli GJ, Hollander JE, Lefebvre P. , et al. Costs of hospital visits among patients with deep vein thrombosis treated with rivaroxaban and LMWH/warfarin. J Med Econ 2016; 19 (01) 84-90
    CrossrefPubMedGoogle Scholar
  • 24 Coleman CI, Turpie AGG, Bunz TJ, Beyer-Westendorf J. Effectiveness and safety of rivaroxaban versus warfarin in patients with provoked venous thromboembolism. J Thromb Thrombolysis 2018; 46 (03) 339-345
    CrossrefPubMedGoogle Scholar
  • 25 Coleman CI, Peacock WF, Bunz TJ, Beyer-Westendorf J. Effectiveness and safety of rivaroxaban versus warfarin in patients with unprovoked venous thromboembolism: a propensity-score weighted administrative claims cohort study. Thromb Res 2018; 168: 31-36
    CrossrefPubMedGoogle Scholar
  • 26 Coleman CI, Bunz TJ, Turpie AGG. Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism. Thromb Haemost 2017; 117 (10) 1841-1847
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Larsen TB, Skjøth F, Kjældgaard JN, Lip GYH, Nielsen PB, Søgaard M. Effectiveness and safety of rivaroxaban and warfarin in patients with unprovoked venous thromboembolism: a propensity-matched nationwide cohort study. Lancet Haematol 2017; 4 (05) e237-e244
    PubMedGoogle Scholar
  • 28 Sindet-Pedersen C, Langtved Pallisgaard J, Staerk L. , et al. Comparative safety and effectiveness of rivaroxaban versus VKAs in patients with venous thromboembolism. A Danish nationwide registry-based study. Thromb Haemost 2017; 117 (06) 1182-1191
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46 (03) 399-424
    CrossrefPubMedGoogle Scholar
  • 30 Normand ST, Landrum MB, Guadagnoli E. , et al. Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores. J Clin Epidemiol 2001; 54 (04) 387-398
    CrossrefPubMedGoogle Scholar
  • 31 Allison PD. . Survival Analysis Using SAS: A Practical Guide. 2nd ed. North Carolina: SAS Institute Inc.; 2010
  • 32 Pencina MJ, D'Agostino Sr RB, D'Agostino Jr RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27 (02) 157-172
    CrossrefPubMedGoogle Scholar
  • 33 Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 2011; 20 (06) 560-566
    CrossrefPubMedGoogle Scholar
  • 34 Thigpen JL, Dillon C, Forster KB. , et al. Validity of international classification of disease codes to identify ischemic stroke and intracranial hemorrhage among individuals with associated diagnosis of atrial fibrillation. Circ Cardiovasc Qual Outcomes 2015; 8 (01) 8-14
    CrossrefPubMedGoogle Scholar
  • 35 Granger CB, Alexander JH, McMurray JJV. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
    CrossrefPubMedGoogle Scholar
  • 36 Li XS, Deitelzweig S, Keshishian A. , et al. Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice. A propensity-matched analysis of 76,940 patients. Thromb Haemost 2017; 117 (06) 1072-1082
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Deitelzweig S, Luo X, Gupta K. , et al. Effect of apixaban versus warfarin use on healthcare resource utilization and costs among elderly patients with nonvalvular atrial fibrillation. J Manag Care Spec Pharm 2017; 23 (11) 1191-1201
    PubMedGoogle Scholar
  • 38 Cai J, Preblick R, Zhang Q, Kwong WJ. Utilization of parenteral anticoagulants and warfarin: impact on the risk of venous thromboembolism recurrence in the outpatient setting. Am Health Drug Benefits 2014; 7 (08) 444-451
    PubMedGoogle Scholar
  • 39 Laliberté F, Coleman CI, Bookhart B. , et al. Weekly risk of venous thromboembolism recurrence in patients receiving oral anticoagulants. Curr Med Res Opin 2014; 30 (08) 1513-1520
    CrossrefPubMedGoogle Scholar
  • 40 Lin J, Lingohr-Smith M, Kwong WJ. Incremental health care resource utilization and economic burden of venous thromboembolism recurrence from a U.S. payer perspective. J Manag Care Pharm 2014; 20 (02) 174-186
    PubMedGoogle Scholar
  • 41 Deitelzweig SB, Lin J, Kreilick C, Hussein M, Battleman D. Warfarin therapy in patients with venous thromboembolism: patterns of use and predictors of clinical outcomes. Adv Ther 2010; 27 (09) 623-633
    CrossrefPubMedGoogle Scholar
  • 42 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. ; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
    CrossrefPubMedGoogle Scholar
  • 43 Broder MS, Neary MP, Chang E, Cherepanov D, Katznelson L. Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases. Pituitary 2014; 17 (04) 333-341
    CrossrefPubMedGoogle Scholar
  • 44 Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation 2016; 133 (06) 601-609
    CrossrefPubMedGoogle Scholar