FEATURE
recurrence, the practical approach is to simply switch
to a less burdensome treatment after the initial six
months of LMWH. Again, we don’t have a definitive
answer as to what that treatment should be – whether
it is warfarin or one of the direct oral agents – at
this juncture, but simply switching to some lessburdensome treatment for the patient would be
beneficial. The patient also needs to be aware
and vigilant for signs and symptoms of recurrent
thrombosis. If a recurrent thrombosis occurs, the
threshold to initiate LMWH would certainly be lower.
The one aspect we can’t ignore in this decision is
the financial and lifestyle burden of injectable LMWH
therapy. Both are substantial. Without clear-cut
proof that extending LMWH therapy is better than
switching to an oral agent – say, warfarin or one of the
direct oral anticoagulants – after six months, it is hard
to make the argument to a patient who is weary of
injecting a needle into his or her abdomen every day
that he or she needs to continue to do that.
Dr. Lee: Yes, no one likes injections and they are
expensive. Personally, when I see patients at that
six-month time point, I have a frank conversation
with them about their treatment options. I tell them:
“We have no evidence to tell us which agent to use
at this point. The decision is up to you and how
you feel about continuing injections or switching to
something else.” That’s the point when I review the
available evidence with them.
Surprisingly, many patients choose to remain on
LMWH, even if I give them the option to switch. If
the alternative is warfarin, many would rather not
have to go to a lab for more blood work or have to
closely monitor their diet and drug interactions.
From a quality-of-life and convenience standpoint,
some patients do prefer to just get their daily injection
over with and go about their daily activities – without
having to constantly worry about going to the lab,
what to eat or drink, when their doctor will call with
more dosing instructions.
Patient preference is definitely very important
– especially with the lack of data to guide treatment
decisions. So, I strongly support whatever the patient
decides. A higher-risk patient – for instance, a patient
with metastatic pancreatic cancer or a patient with
progressive tumors unresponsive to chemotherapy
– needs no convincing to stick with the LMWH
injections. Usually, his or her life is complicated
enough without having to get accustomed to a new
treatment regimen and more blood tests.
I tell my patients to think about it this way: “I cannot
tell you what risk you want to bear, but it is my job
to tell you about the risks. As long as you are aware
that you might have another clot if you switch to
oral therapy and you accept that as a potential
consequence, then I support your decision.”
Dr. Garcia: Now, we actually do have quite a bit
of evidence showing that LMWH is superior to
warfarin, but it has not been compared head-to-head
with a direct oral agent. So, while it’s reasonable
to consider patient preference after six months of
therapy, you would need to be sure that the patient
understood that using LMWH injections (rather than
any other anticoagulant) for the first six months is the
preferred, strong recommendation.
Dr. Lee: Unfortunately, though, the guideline panels
don’t ask patients for their opinions. There has always
been an assumption that people would prefer an
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oral therapy over an injectable therapy, but there are
actually good data about the effect on quality of life
to show that cancer patients actually do not mind
injections – especially when weighed against the
downsides of warfarin therapy.6
In my experience, many patients are hesitant to
use one of the newer direct oral anticoagulants when
I present the evidence to them. They are concerned
about the lack of comparative data. Subgroup analyses
from the large, registration trials have shown some
promising evidence against warfarin in highlyselected cancer patients, but it is premature to use
these agents in most patients with cancer-associated
thrombosis. There are now ongoing trials comparing
direct oral anticoagulants with LMWH, but it will be
several years before we have the results.
Many of my patients have said, “I don’t want
to take the risk of dying from a blood clot. I have
accepted that I am struggling with my cancer and I
might die from that. I’ve lost my hair, I am nauseated,
I look like hell, but I put up with all that because I
want the best therapy for my cancer. If I have to inject
myself once a day to avoid having another clot, that
is not such a big deal in the whole scheme of things.”
We should never assume we know what our patients’
preferences are.
“We can all agree that
– even in the absence
of a clinical trial –
anticoagulation would
be the choice over no
anticoagulation at the
six-month point. The
million-dollar question is, though, after
those six months,
how should we treat
these patients?”
—AGNES Y. LEE, MD
Dr. Garcia: That’s a great point. But what about one
exception: the patient who has a thrombosis in the
setting of an imminently curable malignancy? For
instance, diffuse large B-cell lymphoma in a relatively
youn