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ELIQUIS® (apixaban) is indicated for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥75 years, hypertension, diabetes mellitus, symptomatic heart failure (NYHA Class ≥II); treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults; and, prevention of venous thromboembolic events (VTE) in patients who have undergone elective hip or knee replacement surgery.


Real-World Data in VTE

The clinical trial programme for ELIQUIS® is supported by real-world data in patients treated for DVT / PE, including over 17,000 ELIQUIS patients from four US claims databases1,2

Real-world analyses provide a broader understanding of patient outcomes beyond the clinical trial setting, offering additional evidence for your prescribing decisions3

What does this mean?

Real-world data complement the results of RCTs by providing additional information for informed treatment decisions.3

Rationale and study overview

In the Weycker et al. 2018 USA retrospective, real-world analysis, investigators assessed the safety and effectiveness outcomes of ELIQUIS vs. parenteral anticoagulant / warfarin in 35,756 patients with acute DVT / PE, using pooled data from four geographically diverse US claims databases.2

Study endpoints included:2

  • Major bleeding
  • Clinically relevant non-major bleeding
  • Recurrent VTE during the 180-day (maximum) follow-up period

The propensity score-matched cohort design meant ELIQUIS patients were matched to parenteral anticoagulant / warfarin patients based on variables including age, gender, and comorbidities, as well as other factors.2

Confounding errors can be minimised using propensity score matching to account for differences in patient characteristics between treatment groups.

Limitations of real-world data include:3

  • Unable to determine causality: analyses of observational data study associations between variables, but are unable to determine causality
  • Potential selection bias: the results from non-randomised RWD analyses are limited by potential selection bias
  • Varying outcome definitions: outcome definitions may differ between RCTs and RWD studies
  • Potential coding and data errors: certain clinical parameters may not be present in observational data and these analyses are subject to potential coding errors and missing data
  • Limited ability to generalise: generalisability of findings may be limited to the source data population
  • Confounding factors: although comparative analyses are adjusted for patient baseline demographic and clinical characteristics, confounding errors may still be present

ELIQUIS has a superior major bleeding profile with comparable efficacy vs. enoxaparin / warfarin for treatment of VTE as demonstrated in the AMPLIFY RCT, and complemented by the results of a real-world analysis1,2*

The definitions of efficacy / effectiveness and safety endpoints, as well as the assessed patient populations, differed between the above studies.

FOOTNOTES

* In the AMPLIFY RCT, the primary efficacy outcome was recurrent symptomatic VTE or death related to VTE.1 In the Weycker et al. real-world analysis, the effectiveness outcome was recurrent VTE.2

ELIQUIS was compared with subcutaneous enoxaparin and warfarin. Enoxaparin was discontinued when an INR of 2 or more was achieved. The primary safety outcome was adjudicated major bleeding and the secondary safety outcome was the composite of major bleeding and CRNM bleeding. Bleeding was defined as major if it was overt and associated with a decrease in haemoglobin levels of 2 g/dl or more, required 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 study drug, or discomfort or impairment in carrying out activities of daily life.1 Primary efficacy outcome was recurrent symptomatic VTE or death related to VTE.1

AMPLIFY results are presented as RR (95% CI), whereas Weycker et al. 2018 real-world analysis results are presented as HR (using shared frailty models [an extension of the Cox proportional hazards model that adjusts for correlation from matching]).1,2

§ ELIQUIS 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.2 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.2 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 encounter – irrespective of care setting – were not considered as recurrent events.2

CI = Confidence Interval   CRNM = Clinically Relevant Non-Major   DOAC = Direct-acting Oral Anticoagulant   DVT = Deep Vein Thrombosis   
HR = Hazard Ratio   
ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification   ICD-10-CM = International Classification of Disease, Tenth Revision, Clinical Modification   INR = International Normalised Ratio   N = Total number of patients in the ELIQUIS group or the enoxaparin / warfarin group   n = Number of patients with event   PE = Pulmonary Embolism   RCT = Randomised Controlled Trial   RR = Relative Risk   RWD = Real-World Data   VTE = Venous Thromboembolism

REFERENCES

  1. Agnelli G et al. N Engl J Med 2013; 369: 799–808.
  2. Weycker D et al. Thromb Haemost 2018; 118: 1951–1961.
  3. Camm AJ, Fox KAA. Open Heart 2018; 5: e000788.
  4. ABPI. The vision for real-world data: harnessing the opportunities in the UK. September 2011.
  5. ABPI. Demonstrating value with real world data: a practical guide. May 2011.
  6. ELIQUIS® (apixaban) Summary of Product Characteristics. Available at www.medicines.org.uk.