Rivaroxaban for the treatment of deep vein thrombosis and ...

o It is clear that bleed events were taken from the 3 month measure for Hull et al 2006 42
as this data is not available at 12 months.
o It is unclear whether the Hazard Ratios (Table 20 in the MS) 1 used in the MTC
Primary analysis came from the same time points, or different time points, as the
ERG were unable to identify these in the relevant publications.
The specific LMWH used and dose used. As discussed previously in section 3.3.1, there is
debate about whether to assess efficacy of LMWHs as a class of drugs or to treat each
separately. The ERG was previously satisfied that enoxaparin was a reasonable proxy for
LMWH use in England and Wales, in the absence of other direct comparison data. This meta
analysis pools data from trials using three different LMWHs. The doses used appear to be
roughly equivalent to UK doses and it could therefore be argued that they should be of a
largely comparable therapeutic nature. However, the discussion of possible heterogeneity
between these drugs is partial and clinical opinion has not been sought by the manufacturer on
this matter. The MS provides a comparison of Lee 2003, 43 which focussed on dalteparin, with
the results of the Akl et al 31 meta analysis, to show that there is little heterogeneity between
results on the basis of the LMWH used. This analysis is provided in Table 16 (reproduced
from MS), and shows very similar results between the Cochrane review and the Lee 2003 43
study on its own for VTE recurrence. The lack of heterogeneity is not entirely surprising, as
Lee 2003 43 data contributes 672/1018 (66%) of the patient data, and will therefore have
strongly influenced the analysis. In addition, the difference between minor and major
bleeding, which are important factors in this assessment, do look different. The ERG is not
entirely convinced by this test for heterogeneity, and would have liked to see a discussion of
the results of formal heterogeneity tests.
Table 16: Relative effectiveness of long-term LMWH vs LMWH/VKA dual therapy in
VTE patients with cancer. Reproduction of Table 24, page 74 of MS. 1
Cochrane meta-
analysis 31
72
Lee 2003 43
Point
estimate
(95% CI) Point estimate (95% CI)
Recurrence of VTE HR=0.47 (0.32 to
0.71)
HR=0.48 (0.30 to 0.77)
Incidence of minor RR=0.85 (0.53 to RR=0.54 (0.35 to 0.84)
bleeding
1.35)
Incidence of major RR=1.05 (0.53 to RR=1.57 (0.77 to 3.18)
bleeding
2.10)
Notes: The Cochrane meta-analysis was conducted under a random effects model.
HR = hazard ratio, RR = risk ratio.
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