Apixaban supported by real-world data

Results from the AMPLIFY clinical trial are now complemented by real-world data in almost 36,000 patients with acute DVT / PE from four demographically diverse USA claims databases.1,2 Watch the video below for a breakdown of the results by Dr Ander Cohen, Guy’s and St Thomas’ Hospital, King’s College London, UK.

Real-world analyses provide a broader understanding of patient outcomes beyond clinical trial settings, offering additional evidence for your prescribing decisions.3,4 However, limitations exist:

  • Unable to determine causality
  • Potential selection bias
  • Varying outcome definitions
  • Potential dosing and data errors
  • Limited ability to generalise
  • Confounding errors
  • Confounding errors can be minimised using propensity score matching to account for differences in patient characteristics between treatment groups.

The investigators assessed the safety and effectiveness of apixaban vs. parenteral anticoagulant / warfarin, including major bleeding, clinically relevant non-major bleeding, and recurrent VTE.2

RWD complementing results from a randomised controlled trial

In the AMPLIFY trial, apixaban demonstrated a superior major bleeding profile vs. enoxaparin / warfarin.2 In the Weycker et al. real-world analysis, the major bleeding profile of apixaban complemented that from the clinical trial.

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* Apixaban was compared with subcutaneous enoxaparin, followed by warfarin. The primary efficacy outcome was recurrent symptomatic VTE or death related to VTE. The principal safety outcomes were major bleeding alone and major bleeding plus CRNM bleeding. Bleeding was defined as major if it was overt and associated with a decrease in the haemoglobin level of 2 g/dl or more, required the transfusion of two or more units of blood, occurred into a critical site, or contributed to death. CRNM bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, contact with a physician, interruption of the study drug, or discomfort or impairment in carrying out activities of daily life.1
AMPLIFY results are presented as relative risk (95% CI) whereas Weycker et al. real-world analysis results are hazard ratios (95% CI; using shared frailty models [an extension of the Cox proportional hazards model that adjusts for correlation from matching]).1,2
Apixaban was compared with warfarin plus parenteral anticoagulant bridge therapy (which includes enoxaparin). Major bleeding was defined as an acute-care inpatient admission with a principal or first-listed ICD-9-CM / ICD-10-CM diagnosis code for gastrointestinal bleeding, intracranial haemorrhage or other selected types / sites of bleeding, or an ICD-9-CM / ICD-10-CM procedure code for the treatment of bleeding. CRNM bleeding was defined as an acute-care inpatient admission with a secondary diagnosis code or an ambulatory care encounter with a diagnosis code for gastrointestinal bleeding or other non-critical care types / sites of bleeding. Events that met the definitions for both major bleeding and CRNM bleeding were classified as major bleeding; CRNM bleeding events that followed major bleeding events were not considered in analyses of CRNM bleeding. Recurrent VTE was defined as a subsequent acute-care inpatient admission with a corresponding principal / first-listed diagnosis. Admissions occurring within 7 days of the index VTE encounted – irrespective of care setting – were not considered as recurrent events.2

Abbreviations

  • CI = Confidence Interval
  • CRNM = Clinically Relevant Non-Major
  • DVT = Deep Vein Thrombosis
  • HR = Hazard Ratio
  • ICD-9-CM / ICD-10-CM = International Classification of Diseases, 9th / 10th revision, Clinical Modification
  • PE = Pulmonary Embolism
  • RR = Relative Risk
  • VTE = Venous Thromboembolic Events

  1. Agnelli G, Büller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;369:799–808. https://doi.org/10.1056/NEJMoa1302507; PMID: 23808982.
  2. Weycker D, Li X, Wygant GD, et al. Effectiveness and safety of apixaban versus warfarin as outpatient treatment of venous thromboembolism in U.S. clinical practice. Thromb Haemost 2018;118:1951–61. https://doi.org/10.1055/s-0038-1673689; PMID: 30357780.
  3. The Vision for Real World Data – harnessing the opportunities in the UK. Available at www.abpi.org.uk/publications/vision-for-real-world-data.
  4. ABPI. Demonstrating Value with Real World Data. Available at: www.abpi.org.uk/publications/real-world-data.

December 2019
PP-ELI-GBR-6094