Bayer Pharma AG

Essence of this Article

Several major medical registries and non-interventional studies have been initiated to assess real-world outcomes in patients at risk of, or with, venous thromboembolism (VTE). These include: XAMOS – XArelto® in the prophylaxis of post-surgical venous thromboembolism after elective Major Orthopaedic Surgery of hip or knee; GLORY – Global Orthopaedic Registry; IMPROVE – International Medical Prevention Registry on Venous Thromboembolism; ENDORSE – Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting; RIETE – Computerized registry of patients with venous thromboembolism – Registro Informatizado de Pacientes con Enfermedad TromboEmbólica; GARFIELD-VTE – Global Anticoagulant Registry in the FIELD; XALIA – XArelto® for Long-term and Initial Anticoagulation in venous thromboembolism; and PREFER in VTE – Prevention of Thromboembolic Events – European Registry in Venous Thromboembolism.

Venous Thromboembolism (VTE)

  • XAMOS – XArelto® in the prophylaxis of post-surgical venous thromboembolism after elective Major Orthopaedic Surgery of hip or knee
  • GLORY – Global Orthopaedic Registry
  • IMPROVE – International Medical Prevention Registry on Venous Thromboembolism
  • ENDORSE – Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting
  • RIETE – Computerized registry of patients with venous thromboembolismRegistro Informatizado de Pacientes con Enfermedad TromboEmbólica
  • GARFIELD-VTEGlobal Anticoagulant Registry in the FIELD
  • XALIA – XArelto® for Long-term and Initial Anticoagulation in venous thromboembolism
  • PREFER in VTE – Prevention of Thromboembolic Events - European Registry in Venous Thromboembolism

XArelto® in the prophylaxis of post-surgical venous thromboembolism after elective Major Orthopaedic Surgery of hip or knee (XAMOS)

  • Objective: to provide additional information on the benefit–risk assessment of rivaroxaban compared with standard care treatment for VTE prophylaxis
  • This non-interventional study enrolled 17,701 patients in 37 countries between February 2009 and August 2011 from approximately 252 centres worldwide606
  • Enrolled patients were scheduled to undergo elective hip or knee replacement (or hip fracture surgery where indicated) and receive pharmacological VTE prophylaxis
  • During an observation period of 3 months, data was collected on the following outcomes reported as serious or non-serious adverse events:
    • Bleeding events
    • Symptomatic thromboembolic events (deep vein thrombosis [DVT], pulmonary embolism [PE])
    • Uncommon adverse events (incidence rate between 0.1% and 1.0%)
    • All-cause mortality
  • Compared with standard of care606
    • Rivaroxaban was associated with a significantly lower incidence of symptomatic thromboembolic events (odds ratio 0.65; 95% confidence interval 0.49–0.87)
    • Rates of any bleeding event were increased with rivaroxaban, but major bleeding was similar between the treatment arms (odds ratio 1.19; 95% confidence interval 0.73–1.95)
    • Similar incidences of serious adverse events were observed in both treatment arms, and all-cause mortality was ~0.1% in both treatment arms
  • The non-interventional study approach of XAMOS:
    • Confirmed the results of the RECORD clinical trial programme
    • Demonstrated that in routine clinical practice rivaroxaban has a favourable benefit–risk profile in comparison with current standard of care
    • Provided useful additional information additional to that obtained from the RECORD clinical trial programme

For more information visit:

Clinicaltrials.com. http://clinicaltrials.gov/ct2/show/NCT00831714

Related key publications

Turpie AGG, Haas S, Kreutz R et al. A non-interventional comparison of rivaroxaban with standard of care for thromboprophylaxis after major orthopaedic surgery in 17,701 patients with propensity score adjustment. Thromb Haemost 2014;111:94–102. [PubMed].
Turpie AGG, Schmidt AC, Kreutz R et al. Rationale and design of XAMOS: noninterventional study of rivaroxaban for prophylaxis of venous thromboembolism after major hip and knee surgery. Vasc Health Risk Manag. 2012;8:363-70. [PubMed].

Global Orthopaedic Registry (GLORY)

  • Objective: improving patient care through a better understanding of patient demographics, management, and in-hospital and post-discharge outcomes in patients who underwent elective primary total hip or total knee replacement362
  • Data was obtained from 15,020 prospectively enrolled patients from 100 participating hospitals across 13 countries worldwide between the years of 2001 and 2004, with follow­up visits at 3- and 12-months
  • The key findings of the study were:
    • Elective hip and knee replacement is a relatively safe surgical procedure, with very low mortality rates, and good outcomes for most patients – outcomes that were consistent across all 13 countries involved, despite wide practice variations
    • Rates of symptomatic VTE were higher in this real-world registry than in clinical trials
    • Almost all patients received VTE prophylaxis; however, guideline compliance was suboptimal, with thromboprophylaxis use falling over time, despite patients still having an elevated risk of VTE
    • Improved education regarding the nature and content of evidence-based guidelines for VTE prophylaxis in patients who undergo total hip or total knee replacement surgery is required

For more information visit:

The Global Orthopaedic Registry. http://www.outcomes-umassmed.org/GLORY/

Related key publications

Anderson FA, Jr, Agnelli G, FitzGerald G et al. Overview of the Global Orthopaedic Registry (GLORY). Am J Orthop 2010;39:2–4. [PDF].
Waddell J, Johnson K, Hein W et al. Orthopedic practice in total hip arthroplasty and Total knee arthroplasty: results from the Global Orthopaedic Registry (GLORY) Am J Orthop 2010;39:5–13. [PubMed].
Friedman RJ, Gallus A, Gil-Garay E et al. Practice patterns in the use of venous thromboembolism prophylaxis after total joint arthroplasty–insights from the Multinational Global Orthopaedic Registry (GLORY). Am J Orthop 2010;39:14–21. [PDF].
Cushner F, Agnelli G, FitzGerald G et al. Complications and functional outcomes after total hip arthroplasty and total knee arthroplasty: results from the Global Orthopaedic Registry (GLORY). Am J Orthop 2010;39:22–28. [PDF].
Warwick D, Agnelli G, Cushner F et al. Lessons learned from the Global Orthopaedic Registry (GLORY): study design, current practice patterns, and future directions. Am J Orthop 2010;39:29–31. [PDF].
Friedman RJ, Gallus AS, Cushner FD et al. Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty. Curr Med Res Opin 2008;24:87–97. [PubMed].

International Medical Prevention Registry on Venous Thromboembolism (IMPROVE)

  • Objective: to assess physician practices in the provision of prophylaxis against VTE in acutely ill hospitalized medical patients
  • Prospective cohort study in a population of over 15,000 hospitalized acutely ill medical patients from 52 hospitals in 12 countries364
  • Between July 2002 and September 2006, IMPROVE collected, analysed and published data on:
    • Clinical incidence and risk factors for the development of VTE364, 365
    • Provision of VTE prophylaxis364, 365
    • Bleeding event incidence and risk factors for bleeding363
  • Key endpoints include:
    • Prophylaxis type and duration
    • Death
    • Clinically apparent VTE
    • Bleeding within 3 months of hospital discharge
  • Key findings
    • Only 60% of patients who should have received guideline-recommended VTE prophylaxis actually received it, which is suboptimal
    • Practices varied considerably, with intermittent pneumatic compression being the most commonly used form of VTE prophylaxis in the US (22% of patients), whereas this was rarely used (0.2%) in other countries
    • Unfractionated heparin was the most commonly used drug for VTE prophylaxis in the US (21% of patients), whereas in other countries, this was low molecular weight heparin (40%)

For more information visit:

International Medical Prevention Registry on Venous Thromboembolism. http://www.outcomes-umassmed.org/IMPROVE/
In-hospital VTE and bleeding risk model calculator: http://www.outcomes-umassmed.org/IMPROVE/risk_score/index.html

Related key publications

Spyropoulos AC, Anderson FA Jr, Fitzgerald G et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011;140:706–714. [PubMed].
Decousus H, Tapson VF, Bergmann JF et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011;139:69–79. [PDF].
Tapson VF, Decousus H, Pini M et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007;132:936–945. [PDF].

Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE)

  • Objective: to evaluate the prevalence of VTE risk and thromboprophylaxis practices in the acute hospital care setting
  • ENDORSE was a cross-sectional observational registry involving 358 acute care hospitals in 32 countries between August 2006 and January 2007366, 367
  • Of the 68,183 patients enrolled into ENDORSE, 45% were admitted to a surgical ward, and the remaining 55% admitted to a medical ward
  • 64.4% of surgical patients, and 41.5% of medical patients were at risk of VTE368
    • Of these patients, only 58.5% of surgical patients, and 39.5% of medical patients received guideline-recommended VTE prophylaxis
  • 92.5% of patients who underwent major surgery were at risk of VTE – use of prophylaxis varied according to major surgery type, ranging from:
    • 86.0% for orthopaedic surgery
    • 53.8% in urologic/gynaecologic procedures
    • 53.6% in other procedures
  • In real-world clinical practice, VTE prophylaxis for surgical and medical patients is not always compliant with guidelines and could be improved

For more information visit:

Epidemiologic international day for the evaluation of patients at risk for venous thromboembolism in the acute hospital care setting. http://www.outcomes-umassmed.org/ENDORSE/

Related key publications

Bergmann JF, Cohen AT, Tapson VF et al. Venous thromboembolism risk and prophylaxis in hospitalized medically ill patients: the ENDORSE global survey. Thromb Haemost 2010;103:736–748. [PubMed].
Kakkar AK, Cohen AT, Tapson VF et al. Venous thromboembolism risk and prophylaxis in the acute care hospital setting (ENDORSE survey): findings in surgical patients. Ann Surg 2010;251:330–338. [PubMed].
Anderson FA Jr, Goldhaber SZ, Tapson VF et al. Improving practices in US hospitals to prevent venous thromboembolism: lessons from ENDORSE. Am J Med 2010;123:1099–1106.e8. [PubMed].
Cohen AT, Tapson VF, Bergmann JF et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008;371:387–394. [PubMed].

Computerized registry of patients with venous thromboembolism – Registro Informatizado de Pacientes con Enfermedad TromboEmbólica (RIETE)

  • Objective: to provide an evaluation of treatment options to aid physicians’ treatment decisions to specifically reduce mortality, VTE recurrence and bleeding complications
  • Initiated in March 2001, RIETE is an ongoing multidisciplinary project aimed at obtaining an extensive data registry of consecutive patients with symptomatic acute DVT or PE607 – more than 45,000 patients have been enrolled to date
  • The registry includes details of each patient's:
    • Clinical status, including any coexisting or underlying conditions
    • Type, dose, duration and outcome (during the first 3 months of therapy) of antithrombotic treatment
  • Study endpoints:
    • Clinically recognized (and objectively confirmed) recurrences of VTE
    • Major and minor bleeding complications
    • Death
  • Over 80 manuscripts have been published reporting data from the RIETE registry, or have used RIETE data for decision analysis or pharmacoeconomic modelling. Key insights include:
    • Patients with intermediate/high probabilities of PE will benefit from pre-emptive (i.e. before diagnosis is confirmed) anticoagulation608
    • The presence of silent PE in patients presenting with DVT is associated with an increased incidence of symptomatic PE in the first 15 days of anticoagulant therapy609
    • Patients who present with acute symptomatic PE and have concomitant DVT are twice as likely to die than patients presenting with symptomatic PE without concomitant DVT610
    • Patients who develop VTE as a hospital inpatient have a significantly higher risk of death from PE than patients who develop VTE as an outpatient611
    • RIETE data has been used to determine predictive variables for major bleeding events in patients who present with acute VTE612

For more information visit:

Computerized registry of patients with venous thromboembolism. https://www.riete.org/info/general/index.php

Related key publications
Tzoran I, Brenner B, Papadakis M et al. VTE registry: what can be learned from RIETE? Rambam Maimonides Med J 2014;5:e0037. [PubMed].
Blondon M, Righini M, Aujesky D et al. Usefulness of preemptive anticoagulation in patients with suspected pulmonary embolism: a decision analysis. Chest 2012;142:697–703. [PubMed].
Tzoran I, Saharov G, Brenner B et al. Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs. J Thromb Haemost 2012;10:564–571. [PubMed].
Jiménez D, Aujesky D, Díaz G et al. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2010;181:983–991. [PubMed].
Maestre A, Sánchez R, Rosa V et al. Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry. Eur J Intern Med 2010;21:377–382. [PubMed].
Ruíz-Giménez N, Suárez C, González R et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008;100:26–31. [PubMed].

Global Anticoagulant Registry in the FIELD (GARFIELD-VTE)

  • Objective: to describe patterns of acute and long-term treatment and outcomes in global VTE patient populations that are representative of those encountered in daily clinical practice in more than 20 countries worldwide
  • The registry was launched in 2013 and is designed to describe:
    • Treatment duration and reasons for cessation of therapy
    • The incidence of complications, practical aspects of patient management, healthcare resource use and treatment satisfaction
    • Incidences of VTE recurrence, major bleeding, post-thrombotic syndrome, venous ulcers and chronic thromboembolic pulmonary hypertension

For more information visit:
Global Anticoagulant Registry in the FIELD (GARFIELD-VTE). [Link].

XArelto® for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA)

  • Objective: prospective, non-interventional, observational clinical study to investigate the incidence of recurrent of VTE, major bleeding and mortality, as well as other cardiac and symptomatic thromboembolic events, treatment satisfaction and adherence, in adult patients with a diagnosis of acute DVT treated with rivaroxaban or traditional standard of care613
  • Patients from Canada and Europe with an indication for anticoagulation for at least 12 weeks are eligible for inclusion and the planned enrolment is 4800613
  • The study duration is 12 months after the end of enrolment613

Related key publications
Ageno W, Mantovani LG, Haas S et al. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J 2014;12:16. [PubMed].

For more information visit:
Clinicaltrials.gov. http://www.clinicaltrials.gov/ct2/show/NCT01619007?term=NCT01619007&rank=1

PREvention oF thromboembolic events – European Registry in Venous ThromboEmbolism (PREFER in VTE)

  • Objectives are to:
    • Collect data on the quality of life and treatment satisfaction of patients with VTE
    • Gather insights into patient management in the acute phase and the prevention of recurrent thromboembolic events
    • Investigate the economic burden of VTE treatment
  • PREFER in VTE is a multi-centre, prospective registry with a one-year follow-up
  • The registry will collect real-life data from more than 4000 patients with VTE across seven European countries

For more information visit:

PR Newswire. European patient registry in venous thromboembolism (VTE) - PREFER in VTE - enrols first patient. 2013. Available at: http://www.prnewswire.com/news-releases/european-patient-registry-in-venous-thromboembolism-vte---prefer-in-vte---enrols-first-patient-190028131.html. Accessed 09 January 2015.


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