|
Dr. Fagan, the ACCP group could not make a specific
recommendation on the use of combination therapy for PAH
patients because we don’t have an extensive evidence base
to guide us. What is your general approach to combination
therapy? Do you use epoprostenol together with bosentan?
How about sildenafil? How do you decide?
|
 Karen
Fagan, MD
Assistant Professor
Division of Pulmonary Sciences/Critical Care Medicine
University of Colorado Health Sciences Center
Denver, Colorado
|
The potential for combination therapy in PAH is very
appealing but to date the data supporting this are limited.
Broadly speaking, we consider combination therapy in two
general groups of patients. First, for patients who have
been receiving treatment with aggressive therapy (ie,
epoprostenol) and who have had a very good clinical response,
we consider adding additional therapy with the goal of
withdrawing epoprostenol and using a less complicated,
less risky therapy. Second, when patients have evidence
of significant clinical worsening while receiving aggressive
treatment, usually with epoprostenol, we will consider
combination therapy with the hope of stabilizing or reversing
disease progression.
Thus far we have the most experience with the addition
of bosentan to treatment with epoprostenol. As was suggested
by the BREATHE-2 trial, the combination appears to be
safe and we have not experienced significant adverse events
with this
combination.1 Occasionally we decrease
the dose of epoprostenol with the initiation of bosentan
to lessen the possibility of side effects, especially
hypotension. As to the success of combination treatment,
we have had a few patients who have
discontinued epoprostenol with addition of bosentan who
have remained clinically stable. It is less clear if we
have achieved additional benefit in very ill patients
in whom we have added bosentan to epoprostenol. Some patients
seem to have some improvement while others do not.
In patients who were treated initially with bosentan
and who demonstrate clinical worsening, we have generally
added epoprostenol as the next therapy. The decision on
whether to continue bosentan is difficult, but we generally
continue both
until the patient has initiated and tolerated epoprostenol
for several weeks and then consider whether to continue
bosentan or not.
Our experience with other combinations such as addition
of sildenafil to other therapy is very limited at present.
A large clinical trial recently evaluated the use of sildenafil
in patients with PAH and preliminary results suggest benefit.
This will
likely open the doors to further exploration of combination
therapy.
Reference
1. Humbert M, Barst RJ, Robbins IM, Channick
RN, Galie N, Boonstra A, et al. Combination of bosentan
with epoprostenol in pulmonary arterial hypertension:
BREATHE-2. Eur Respir J. 2004;24(3):353-9.
|
