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The ACCP group made the following recommendation
regarding the therapeutic approach to the class III patient
with PAH: Patients with PAH in functional class III who
are not candidates for, or who have failed, CCB therapy
are candidates for longterm therapy with: Endothelin-receptor
antagonists (bosentan). Level of evidence: good; benefit:
substantial; grade of recommendation: A. IV epoprostenol.
Level of evidence: good; benefit: substantial; grade of
recommendation: A. Subcutaneous treprostinil. Level of
evidence: fair; benefit: intermediate; grade of recommendation:
B. Inhaled iloprost. Level of evidence: fair; benefit:
intermediate; grade of recommendation: B. Beraprost. Level
of evidence: good; benefit: conflicting; grade of recommendation:
I.
Dr Hill, is your general approach the same as that
presented in the above recommendations? How do you decide
whether to use epoprostenol, treprostinil, or bosentan?
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Nicholas Hill, MD
Professor and Chief
Pulmonary, Critical Care, and Sleep Division
Tufts-New England Medical Center
Boston, Massachusetts
 Iona
Preston, MD
Codirector, Pulmonary Hypertension Center
Tufts-New England Medical Center
Boston, Massachusetts
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Iona Preston, MD, codirects our Pulmonary Hypertension
Center at Tufts-New England Medical Center, and I have
asked her to join me in answering. Although we agree in
principle with the ACCP guidelines for functional class
III PAH patients, we often don’t follow them. First,
we divide functional class III patients into two subcategories;
IIIA and IIIB. IIIA patients are limited in their activities
of daily living, but have been stable for at least several
months. IIIB patients have similar functional limitations,
but have had progressive symptoms over the previous several
months. We consider endothelin-receptor antagonists like
bosentan to be
the agents of first choice for class IIIA patients, but
don’t feel comfortable administering them to IIIB
patients (or class IV patients, for that matter) because
these patients aren’t sufficiently stable to wait
out the 2 to 3 months that can elapse before a substantial
favorable response occurs.
We prefer prostacyclins for IIIB patients, because in
our experience these provide the greatest chance of a
rapid, favorable response. We often start therapy in these
patients with subcutaneous treprostinil in preference
to intravenous epoprostenol because of the convenience
and safety advantages. If patients can’t tolerate
the infusion site pain, we convert treatment to intravenous
epoprostenol.
Our institution has a busy liver transplant center, and
we have a fair number of patients with portopulmonary
hypertension. Although there are case reports in the literature
of patients with portopulmonary hypertension successfully
treated with endothelin-receptor antagonists, we prefer
subcutaneous treprostinil for such patients in functional
class III, because we want to avoid adding potential liver
toxins to their medical regimen. Our experience is that
such patients respond very well to treprostinil.
Our center is also participating in multicenter trials
to evaluate the efficacy and safety of sitaxsentan and
ambrisentan. We enter some class IIIA patients into these
trials because we believe there is a great need for more
therapeutic choices and more efficacious medications.
Thus, class IIIA patients who wish to try promising new
investigational agents are entered into one of these trials.
Some of our class IIIA and IIIB patients have started
receiving sildenafil as a first-line therapy. Some were
enrolled in the Pfizer-supported multinational pivotal
phase III trial of sildenafil and continue to use the
drug as a sole therapy, now up to 2 years later. Others
had difficulty obtaining insurance coverage for other
agents (a patient with sarcoidosis, for example) and still
others requested sildenafil
after reading about it on the Internet or in the media,
deciding that they preferred it to other currently available
therapies. These patients were counseled that sildenafil
has not yet been proven to be safe and effective for the
treatment of PAH, nor has it been approved by the FDA
for this indication. In our experience, most private insurers
and Medicaid in the New England region will reimburse
for sildenafil to
treat PAH. As much as possible, we obtain free samples
for those who are unable to get insurance coverage. Our
anecdotal experience using sildenafil for class III PAH
patients has been favorable, and the preliminary results
of the pivotal trial support our experience.
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