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New Guidelines Include Bosentan as a Recommended Treatment for Pulmonary Arterial Hypertension

LONDON, June 21/PRNewswire/ -- The Taskforce of the 3rd World Symposium on Pulmonary Arterial Hypertension today published new evidence-based guidance for the classification, diagnosis and treatment of patients with Pulmonary Arterial Hypertension (PAH). The guidelines, published in the Journal of the American College of Cardiology(1), graded Tracleer(R) (bosentan), the first oral dual ERA, with the highest "level of evidence", (grade A; see editors notes), for the treatment of patients with IPAH (idiopathic pulmonary arterial hypertension) class III and PAH related to connective tissue disease.

The World Symposium provided leading experts in the field of PAH with the opportunity to formally update the previously existing 1998 WHO guidelines, based on new evidence based research, clinical experience and improvements in knowledge of the disease and the treatments available. The new insights reflect major advances over the last five years in the understanding of mechanisms of PAH disease development, diagnostic processes involved and in approaches to treatment for PAH, and clearly show the extent of progress within this disease area since the previous WHO statement. The following two key changes were made:

New PAH nomenclature and treatment algorithm
Specific changes included replacing the term Primary Pulmonary Hypertension (PPH) with the term Idiopathic Pulmonary Hypertension (IPAH), to avoid the widespread and potentially confusing use of the term secondary PAH to describe conditions related to Pulmonary Hypertension (PH).

In addition, an evidence-based treatment algorithm has been proposed, based on recent advances in controlled clinical trials illustrating the strength of evidence for each of the treatments available for PAH. The algorithm proposes that treatments are categorised from A (indicating a strong evidence base) to C (indicating a weaker evidence base) according to the number of favourable randomized clinical trials. The Taskforce noted that Tracleer(R) (bosentan), the only orally available endothelin receptor antagonist (ERA), has been successfully tested in two randomised controlled clinical trials, and as such was awarded a grade of A for the treatment of patients with Class III IPAH and PAH related to connective tissue disease.

About the 3rd World Symposium on PAH
The 3rd World Symposium on Pulmonary Arterial Hypertension (PAH) was a forum for the presentation and discussion of overviews on a number of aspects of this devastating condition, including Pathology and Pathobiology, Genetics, Epidemiology, Nomenclature and Classification, Diagnosis and Assessment, Medical Treatments, Interventional and Surgical Treatments and Future Directions.

About the Proposed Treatment Algorithm for PAH class III and IV patients
The revised PAH treatment algorithm is restricted to patients in NYHA functional class III and IV, as currently insufficient data exists for class I and II patients. The treatment algorithm may change with the availability of new data from clinical trials.

Level of Evidence is based on the number of favourable randomised clinical trials as follows:
Grade A: Data derived from multiple randomised clinical trials or meta-analyses;

Grade B: Data derived from a single randomised clinical trial or from multiple randomised clinical trials with heterogeneous results;

Grade C: Data derived from small nonrandomised studies and or consensus opinion of experts.

About PAH
Around 100,000 people in Europe and the US currently suffer from pulmonary arterial hypertension, which includes IPAH and PAH related to other diseases such as scleroderma(2). Early detection and diagnosis is extremely important in order to provide appropriate treatment that may significantly improve patients' lives. Unfortunately, diagnosis can often be delayed because initial symptoms are unspecific (i.e. breathlessness) and therefore go undetected or are attributed to other diseases.

About Tracleer(R)
Tracleer(R), the first oral dual endothelin receptor antagonist, has demonstrated its efficacy in two pivotal, placebo-controlled studies(3,4). Tracleer(R) has shown statistically significant improvements in the primary efficacy endpoint of exercise capacity with patients achieving a significantly greater, and clinically meaningful increase in walking distance compared to placebo.

Clinical trials have also demonstrated Tracleer(R)'s efficacy in significantly decreasing dyspnea (shortness of breath), one of the most debilitating symptoms for people with PAH. Additionally, treatment with Tracleer(R) is also associated with a significant delay in disease progression (the time to clinical worsening)(4). Clinical worsening is defined as combined endpoint of death, hospitalization or discontinuation due to worsening PAH.

In clinical trials leading to the marketing approval of the drug, approximately 11% of PAH patients receiving Tracleer(R) experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take Tracleer(R).

Tracleer(R) is currently approved and available in the United States, the European Union, Canada, Australia, Israel and Switzerland for the treatment of Pulmonary Arterial Hypertension (PAH).

References:
(1). Galiè N and Rubin L. Pulmonary Arterial Hypertension Epidemiology, Pathobiology, Assessment and Therapy. JACC 2004;43:12(supplement S)

(2). Zaret BL et al. Yale University School of Medicine Heart Book. New York: Hearst Books, 1992. p.178.

(3). Channick R et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo controlled study. Lancet 2001; 358:1119-23

(4). 5 Rubin LJ, Badesch DB, Barst RJ, Galie N, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002:346:896-903

Source: Actelion Ltd.

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