title: Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient.
abstract: Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA) that has been shown in a large randomized placebo-controlled trial (BREATHE-1) to be effective at improving exercise tolerance in patients with PAH in functional class III and IV. Further studies have been conducted showing: benefit in smaller subgroups of PAH, eg, congenital heart disease, efficacy in combination with other PAH therapies, eg, sildenafil, improved long-term survival compared with historical controls. More recently, controlled trials of new ERAs have included patients with milder symptoms; those in functional class II. Analysis of the functional class II data is often limited by small numbers. These trials have generally shown a similar treatment effect to bosentan, but there are no controlled trials directly comparing these new ERAs. The EARLY trial exclusively enrolled functional class II patients and assessed hemodynamics at 6 months. Though significant, the reduction in pulmonary vascular resistance is merely a surrogate marker for the intended aim of delaying disease progression. Significant adverse effects associated with bosentan include edema, anemia and transaminase elevation. These may preclude a long duration of treatment. Further studies are required to determine optimum treatment strategy in mild disease.
authors.affiliation: Department of Cardiology, Royal Free Hospital, London, UK. cjvalerio@doctors.net.uk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Valerio
authors.forename: John G
authors.initials: JG
authors.lastname: Coghlan
mesh_terms: D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D065130:Endothelin A Receptor Antagonists; D017079:Exercise Tolerance / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan
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