Apixaban for the prevention of venous thromboembolism in people ...

Comment
– The discount rates and perspective are in line with the NICE reference case.
– Since patients are 65 to 68 years of age when they enter the model, a 35 year time horizon
seems to reflect lifetime. After 35 years 98% of the cohort had died.
5.2.6 Treatment effectiveness
Efficacy and safety of the treatments is modelled in line with the corresponding endpoints in
the ADVANCE, 16, 18 RECORD, 25, 27 RE-MODEL and RE-NOVATE 21, 23 trials:
‘total VTEs and all deaths’ (all adjudicated VTE and all cause death and adjudicated,
symptomatic or asymptomatic DVT, non-fatal PE and death from any cause)
‘total bleeds’ (bleeding at the surgical site, non-surgical bleeding events, clinically
relevant non-major bleeding and minor bleeding events).
It should be noted that this approach to model the efficacy and safety of the comparators does
not allow for differences between types of bleed (major, minor) and types of VTE
(symptomatic, asymptomatic) for each comparator individually.
Enoxaparin was the reference treatment in the model. In the MS it was stated that both the
reference treatment rates and the apixaban relative risk were taken from the ADVANCE-2 16
for TKR patients, and from the ADVANCE-3 18 for THR. In the absence of head to head RCT
evidence for apixaban 2.5 mg bd versus rivaroxaban 10 mg od, and dabigatran 220 mg od, an
adjusted indirect comparison approach was adopted. It was stated that because data for an
indirect comparison with fondaparinux 2.5 mg od was not available, apixaban could not be
compared with fondaparinux in the model. A primary efficacy population was used for ‘total
VTEs and all deaths’, as the asymptomatic DVT outcome can only be detected via an
evaluable venogram.
Table 5.3 Composite VTE and bleed rates (indirect comparison Group 1) (Table 58 MSpage
133)
THR:
TKR:
THR:
TKR:
All VTE & All All VTE & All Any bleeding Any bleeding
cause death cause death (95% CI) (95% CI)
(95% CI) (95% CI)
Primary efficacy population
analysis ITT analysis
Baseline risk
(Enoxaparin 40mg OD) 4.58% 26.29% 9.39% 8.75%
0.359
0.618
0.93
0.83
Apixaban RR
(0.232–0.555) (0.514–0.743) (0.81–1.08) (0.64–1.06)
0.3
0.507
1.02
1.02
Rivaroxaban RR
(0.18–0.51) (0.395–0.651) (0.81–1.29) (0.72–1.44)
0.887
0.965
1.07
0.96
Dabigatran RR
(0.696–1.131) (0.822–1.133) (0.86–1.34) (0.76–1.22)
42
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