study outcome was the composite of recurrent
symptomatic VTE and major bleeding
complications (as assessed by an independent
committee unaware of the study arm) occurring
within 12 months of recruitment according to an
intention-to-treat analysis (thus, irrespective of
protocol violations and of drug discontinuation
after the first six months). It is worth mentioning
that patients randomised to edoxaban had, on
average, one more month of anticoagulation
compared with patients allocated to dalteparin.
A similar proportion of patients allocated to
the two study arms developed the main study
outcome: 67/522 patients (13.8%) randomised
to edoxaban and 71/524 (13.5%) allocated to
dalteparin. Of interest, symptomatic recurrent
VTE developed in 41 patients (7.9%) randomised
to edoxaban and in 59 (11.3%) allocated to
dalteparin; major bleeding complications
developed in 36 (6.9%) and 21 (4.0%), respectively
(not significant differences). Interestingly enough,
severe bleeding complications (including fatal
bleeding, intracranial, retroperitoneal or critical
bleeding) developed in similar proportions (12
patients) in each of the two treatment groups.
In addition, most major bleedings that developed
in the edoxaban group were gastrointestinal
bleedings in patients recruited because of
gastrointestinal cancer. Also the rate of clinically
symptomatic non-major bleeding was remarkably
lower in patients treated with dalteparin (11.1%)
than in those receiving edoxaban (14.6%).
In a second smaller clinical trial,
approximately 400 patients with a recent
(either symptomatic or asymptomatic) CAT
were randomised to receive from the beginning
(without an initial parenteral treatment) either
subcutaneous dalteparin (same schedule as the
Hokusai/K) or oral rivaroxaban (15mg tid for the
first three weeks, followed by 20mg oid
thereafter) for six months. 15
The results of the Select/D study are consistent
with those observed in the Hokusai/K. While the
benefit–risk profile of the two drugs was found
to be comparable, compared with dalteparin,
rivaroxaban was associated with a remarkable
reduction in the rate of symptomatic recurrent
VTE (3.9% compared with 8.9%), and a substantial
increase in the rate of major (5.4% vs 3.0%) as well
as non-major clinically relevant (12.3% vs 3.0%)
bleedings. Once again, the rate of severe bleeding
was low in each of the study groups; and what
accounted for the difference in the rate of major
bleedings between edoxaban and dalteparin
most was the occurrence of gastrointestinal
bleedings in those cancer patients with
gastrointestinal cancers who had been allocated
to the edoxaban group.
Conclusions
According to the findings of the first two
head-to-head comparisons between LMWH and
the DOACs for the treatment of CAT, the
following conclusions can be drawn: 1) the
benefit – risk profile of the two drugs categories is
comparable. As the novel drugs are less expensive
and result in a considerable reduction in the
burden and inconveniences for patients compared
with LMWHs, their use in place of heparins is
fully justified; 2) at least in patients who fulfil the
recruitment criteria of the two clinical trials, the
novel drugs are likely to be more effective; 3) they
are associated with a higher haemorrhagic risk,
particularly in patients with gastrointestinal
cancer. In these patients, their use should be
discouraged, as well as in patients who have
problems with intake and absorption of oral
drugs. Anyway, the risk of the most severe
bleeding complications does not seem to differ
between the two drug categories. In conclusion,
an outstanding achievement has been obtained
for the treatment of CAT, particularly desirable
for patients who may require months or years
of anticoagulation.
23
HHE 2018 | hospitalhealthcare.com
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