This information is intended for healthcare professionals based in Ireland.

ADVANCE 3

ADVANCE-3: Phase III trial of efficacy and safety of ELIQUIS® vs. enoxaparin 40 mg OD for prevention of venous thromboembolic events (VTE) for patients undergoing total hip replacement (THR) surgery1

Overview

ADVANCE-3 was a phase III, randomised, double blind trial comparing the efficacy and safety of ELIQUIS® vs enoxaparin for the prevention of VTE in patients undergoing total hip replacement surgery.

ADVANCE-3 Study Design

In this multi-centre, randomised, double-blind trial, patients received either ELIQUIS® 2.5 mg BD, starting 12–24 hours after surgery, or enoxaparin 40 mg OD starting 12 hours (+/-3) before the procedure. 2708 patients were randomised to ELIQUIS®; 2699 were randomised to enoxaparin.

Subjects underwent either elective THR or revision of a previously inserted hip prosthesis. Treatment was continued for 32–38 days after surgery.

In hospital all patients were assessed daily for symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) as well as bleeding complications. Bilateral venographic studies were scheduled 32–38 days after surgery. All venograms were adjudicated by an independent central adjudication committee.

For primary efficacy analysis, 1949 patients in the ELIQUIS® (apixaban 2.5 mg tablets) group and 1917 in the enoxaparin 40 mg OD group were eligible.

The primary efficacy endpoint was Total VTE/all-cause death (composite of asymptomatic and symptomatic VTE, non-fatal PE and all-cause death), whereas the secondary efficacy endpoint was Major VTE (composite of asymptomatic and symptomatic proximal DVT, non-fatal PE and VTE-related death).

ADVANCE-3 Efficacy Results

ELIQUIS® demonstrated superior efficacy vs. enoxaparin 40 mg once daily in the prevention of VTE following THR.1

In ADVANCE-3 the incidence of symptomatic VTE and VTE-related death was low and similar to enoxaparin 40 mg OD12:4/2708 patients (0.1%) in the ELIQUIS® group vs. 10/2699 patients (0.4%) in the enoxaparin group (P=0.11).

ADVANCE-3 Trial: ELIQUIS® superior efficacy in Total VTE and Major VTE1

advance 3 eliquis (apixaban) trial superior efficacy in total vte and major vte image

Adapted from reference 1
Total VTE/all cause death measured at days 32-38 was a composite of asymptomatic or symptomatic DVT, non fatal PE and death from any cause.
Major VTE was a composite of asymptomatic and symptomatic proximal DVT, non fatal PE and VTE-related death.

ADVANCE-3 Safety Endpoints

ELIQUIS® resulted in no increased bleeding vs. enoxaparin 40 mg once daily following THR.1

Primary safety endpoint was bleeding during treatment (major; Clinically Relevant Non-Major [CRNM]; minor; composite of major and CRNM).1

ADVANCE-3 Trial: treatment period bleeding rates1

advance 3 eliquis (apixaban) trial treatment period bleeding rates image

Adapted from reference 1.
Results include all events occurring after the first dose of enoxaparin (pre-surgery).

ADVANCE-3 Surgical Site Bleeding

ELIQUIS® provided similar rates of surgical site bleeding vs. enoxaparin 40 mg once daily following THR.1

ELIQUIS® resulted in similar rates of surgical site bleeding vs. enoxaparin 40 mg OD following THR.1

Surgical site bleeding was included in the bleeding definition in the ELIQUIS® Phase III trials in major orthopaedic surgery.1

The occurrence of surgical bleeds may be associated with an increased risk of infection.3

Risk Minimisation Materials

The Eliquis (apixaban) Prescriber Guide and Patient Alert Card are risk minimisation materials developed for all indications as an aid to prescribing, in particular they are aimed at increasing awareness about the potential risk of bleeding during treatment with apixaban and providing guidance on how to manage that risk. Printed copies of these educational materials may be obtained by contacting the Bristol-Myers Squibb Medical Information Department (telephone: 1800 749 749; e-mail: medical.information@bms.com). Alternatively, electronic copies can be accessed via the HPRA website at http://www.hpra.ie/homepage/medicines/medicines-information/find-a-medicine.

References:

  1. Lassen MR, Gallus A, Raskob GE, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363:2487-2498.
  2. Lieberman JR, Hsu WK. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am. 2005;87(9):2097-2112.