Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism
Craig I. Coleman
1
University of Connecticut School of Pharmacy, Storrs, Connecticut, USA
,
Thomas J. Bunz
2
Crystal Run Healthcare, Middletown, New York, USA
,
Alexander G. G. Turpie
3
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
› InstitutsangabenFinancial support: This study was supported by Bayer AG, Berlin, Germany. The sponsor had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012–6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19% (95%CI=10–27%) reduction in recurrent VTE and a 21% (95%CI=4–35%) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients’ hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.
Supplementary Material to this article is available at www.thrombosis-online.com.
1
Heit JA,
Cohen AT,
Anderson Frederick AJ.
the VTE Impact Assessment Group.
Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. ASH Annu Meet Abstr 2005; 106: 910.
3
Limone BL,
Hernandez AV,
Michalak D.
et al. Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials. Thromb Res 2013; 132: 420-426.
4
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: 1513-1520.
5
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: 200-203.
7
EINSTEIN Investigators.
Bauersachs R,
Berkowitz SD.
et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
8
EINSTEIN-PE Investigators.
Büller HR,
Prins MH.
et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
9
Prins MH,
Lensing AW,
Bauersachs R.
et al.
EINSTEIN Investigators.
Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11: 21.
10
Mearns ES,
Kohn CG,
Song JS.
et al. Meta-analysis to assess the quality of international normalized ratio control and associated outcomes in venous thromboembolism patients. Thromb Res 2014; 134: 310-319.
11
Erkens PM,
ten Cate H,
Büller HR,
Prins MH.
Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS One 2012; 07: e42269.
13
von Elm E,
Altman DG,
Egger M.
et al. STROBE Initiative The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453-1457.
14
Gandhi SK,
Salmon W,
Kong SX,
Zhao SZ.
Administrative databases and outcomes assessment: An overview of issues and potential utility. J Manag Care Spec Pharm 1999; 05: 215-222.
17
Cunningham A,
Stein CM,
Chung CP.
et al. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 2011; 20: 560-566.
18
Austin PC.
An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46: 399-424.
19
Ageno W,
Mantovani LG,
Haas S.
et al. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol 2016; 03: e12-e21.
20
Gaertner S,
Cordeanu EM,
Nouri S.
et al. Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes. Int J Cardiol 2017; 226: 103-109.
21
Kucher N,
Aujesky D,
Beer JH.
et al. Rivaroxaban for the treatment of venous thromboembolism The SWIss Venous ThromboEmbolism Registry (SWIVTER). Thromb Haemost 2016; 116: 472-479.
22
Schmidt M,
Schmidt SA,
Sandegaard JL.
et al. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 07: 449-490.
24
Mantha S,
Laube E,
Miao Y.
et al. Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study. J Thromb Thrombolysis 2017; 43: 166-171.
25
Lee AY,
Levine MN,
Baker RI.
et al. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer Investigators Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
26
Hull RD,
Pineo GF,
Brant RF.
et al. LITE Trial Investigators Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 2006; 119: 1062-1072.
27
Graham DJ,
Reichman ME,
Wernecke M.
et al. Stroke, bleeding, and mortality risks in elderly medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med 2016; 176: 1662-1671.
