This article summarizes a study that evaluated the efficacy and safety of bosentan for pulmonary arterial hypertension. The study found that patients treated with bosentan had improved exercise capacity and pulmonary function compared to placebo, as well as reduced clinical worsening. Bosentan was well tolerated at a dose of 125 mg twice daily and showed benefits for pulmonary arterial hypertension patients. Long-term experience with bosentan is still needed, but initial results suggest it is an effective oral therapy for pulmonary arterial hypertension.
Part I - Anticipatory Grief: Experiencing grief before the loss has happened
Study review (Bosentan)
1. Article Review
New England Journal of Medicine ,Vol. 346, No. 12 ·
March 21, 2002
27 centers in Europe, North America, Israel, and Australia.
Lewis J Rubin et al
BOSENTANTHERAPY FOR PULMONARY ARTERIAL
HYPERTENSION
By AYG
Ahm.Yehia@gmail.com
2. Introduction
• PAH is Debilitating DiseaseWhere PulmonaryVascular Résistance is increased that may lead to RightVentricular
Failure and Death 1
• Shortness of breath on exertion is one of the earliest manifestations of disease. PAH is further associated with
increasing fatigue and progressive deterioration in exercise capacity; significantly impacting on quality of life
• PAH represents diverse population groups that vary greatly in etiology, disease severity, speed of progression,
prognosis and response to treatment.
• There is increasing evidence that Endothelin-1 has a pathogenic role in pulmonary arterial hypertension and that
blockade of Endothelin receptors may be beneficial.
• Endothelin-1 is a potent endogenous vasoconstrictor & smooth-muscle mitogen that is overexpressed in the
plasma and lung tissue of patients with primary pulmonary hypertension and scleroderma .Its actions are
mediated by two receptors ,ETA and ETB .
5. Study design
1ry endpoint:Change in exercise capacity (walking distance)
2ry endpoint:Change in Borg Dyspnea Index, change inWHO
functional class, Time to the clinical worsening
6. Inclusion &
Exclusion
criteria
Symptomatic, severe pulmonary arterial
hypertension (WHO functional class III or IV)
Treatment with anticoagulant drugs,
vasodilators, diuretics, cardiac glycosides, or
supplemental oxygen
Either primary or associated with connective-
tissue disease (scleroderma or systemic lupus
erythematosus)
Base-line six minute walking distance between
150 - 450 m,
Resting mean pulmonary-artery pressure <25
mm Hg,
Pulmonary capillary wedge pressure of >15 mm
Hg, and pulmonary vascular resistance <240
dyn·sec·cm¡5
Exclusion
If started or stopped any therapy
for pulmonary arterial
hypertension within one month
before screening
If received or had been
scheduled to receive long-term
treatment with epoprostenol
within three months before
screening.
To avoid potential drug
interactions, patients were also
excluded if they were receiving
Glyburide (Glibenclamide) or
cyclosporine
N.B. For ethical reasons, eligible patients in class IV were also required to have a sufficiently stable clinical status to enable
them to participate in a placebo-controlled trial
Inclusion
7.
8. Results
• Patients treated with Bosentan had an improved six-minute walking
distance
• The mean difference between the placebo group and the combined
Bosentan groups was 44 m (95 percent confidence interval; P<0.001)
• Bosentan also improved the Borg dyspnea index andWHO functional
class and increased the time to clinical worsening
(atWeak 16)
Conclusion
• The endothelin-receptor antagonist Bosentan is beneficial in patients
with PAH and is well tolerated at a dose of 125 mg twice daily
• Endothelin-receptor antagonism with oral Bosentan is an effective
approach to therapy for PAH.
Results &
Conclusions
9. Discussion
In a preliminary study of patients with PAH, Bosentan improved exercise
capacity and cardiopulmonary hemodynamics.4
In this study Bosentan was found to reduce significantly the risk of clinical
worsening and improved exercise capacity in patients with severe PAH
Treatment with 125 mg of Bosentan twice daily was not associated with a
significant increase in adverse events when compared with placebo.
However, increasing the dose to 250 mg twice daily led to a greater
frequency of increased aminotransferase levels.
Cases of elevated aminotransferase levels observed with Bosentan
treatment are dose-Dependent in incidence and severity
125 mg twice daily is the clinically preferable dose.
limitations of the present study
is that patients with PAH secondary to other diseases, such as portal
hypertension or infection with the HIV , were not included.
long-term clinical experience is still needed.
