Real-world-data

VTE-DVT / PE Real-World Data

The clinical trial programme for ELIQUIS® is now supported by real-world data in patients treated for DVT / PE, including over 17,000 ELIQUIS patients from four US claims databases^1,2

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

What does this mean?

Real-world data complement the results of RCTs by providing additional information for informed treatment decisions.⁵

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 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.

Real-world data provide a broader understanding of patient outcomes beyond the clinical trial setting, offering additional evidence for prescribing decisions.⁵

Limitations of real-world data include:⁵

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 dosing 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 a RCT and complemented by results shown in real-world analyses^1,2*

Study results

In the AMPLIFY trial, ELIQUIS demonstrated a superior major bleeding proﬁle vs. enoxaparin / warfarin.¹ In the Weycker et al. 2018 real-world analysis, the major bleeding proﬁle of ELIQUIS complemented that from the clinical trial.²

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

^*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 (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 VTE in adult patients who have undergone elective hip or knee replacement surgery.⁶

Footnotes:

^† ELIQUIS was compared with subcutaneous enoxaparin and warfarin. Enoxaparin was discontinued when an INR of 2 or more was achieved. Primary safety outcome was adjudicated major bleeding the secondary safety outcome was the composite of major 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 the incidence of the adjudicated composite of 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 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
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:

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

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance at www.hpra.ie

Adverse reactions should also be reported to Bristol-Myers Squibb Medical Information on 1 800 749 749 or medical.information@bms.com