ADVANCE-2 was a phase III, randomised, double-blind study comparing the efficacy and safety of ELIQUIS® vs enoxaparin for the prevention of VTE in patients undergoing total knee replacement surgery.
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 (+/-3) hours before the procedure. 1528 patients were randomised to ELIQUIS®; 1529 were randomised to enoxaparin.
Subjects underwent either unilateral or same-day bilateral elective knee replacement. Treatment was continued for 10–14 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 10–14 days after surgery. All venograms were adjudicated by an independent central adjudication committee.
For primary efficacy analysis, 976 patients in the ELIQUIS group and 997 in the enoxaparin 40 mg OD dosing group were eligible.
The primary efficacy endpoint was the Total VTE/all-cause death (composite of asymptomatic and symptomatic VTE, non-fatal PE and all-cause death), whereas the secondary efficacy endpoint was the major VTE (composite of asymptomatic and symptomatic proximal DVT, non-fatal PE and VTE-related death).
ELIQUIS® demonstrated superior efficacy vs. enoxaparin 40 mg OD following total knee replacement1
In ADVANCE-2, the incidence of symptomatic VTE or VTE-related death with ELIQUIS® was low and similar to enoxaparin1:
RRR: relative risk reduction
ARR: absolute risk reduction
NNT: number needed to treat
Total VTE/all cause death measured at days 10-14 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
ELIQUIS® provided no increased bleeding vs. enoxaparin 40 mg once daily following total knee replacement.1
Primary Safety Endpoint—Bleeding during treatment (major; clinically relevant non-major [CRNM]; minor; composite of major and CRNM).1
Adapted from reference 1
Results include all events occurring after the first dose of enoxaparin (pre-surgery).
ELIQUIS® provided similar rates of surgical site bleeding vs. enoxaparin 40 mg OD following total knee replacement.1
Surgical site bleeding was included in the bleeding definition in the ELIQUIS® Phase III trials in major orthopaedic surgery.1,2
The occurrence of surgical bleeds may be associated with an increased risk of infection.3
Adapted from reference 1
Results were based on investigator reports. Not powered to detect statistically significant differences.