Pulmonary Arterial Hypertension, November 2005

Susan Steinbis, RN, ACNP The Pulmonary Hypertension Journal Scan is the clinician's guide to the latest clinical research findings from JAMA, The New England Journal of Medicine, CHEST, and other journals of interest. Short summaries of feature articles include links to the article abstracts when available. (Access to full-text articles usually requires registration at the specific journal's Web site.)

FromHeart  ( Volume 91, Number 11 )

Effect of the Oral Endothelin Antagonist Bosentan on the Clinical, Exercise, and Haemodynamic Status of Patients With Pulmonary Arterial Hypertension Related to Congenital Heart DiseaseApostolopoulou SC, Manginas A, Cokkinos DV, Rammos S 
Heart.  2005;91(11):1447-1452

Congenital heart disease (CHD) with Eisenmenger's physiology is a condition that can cause pulmonary arterial hypertension (PAH). PAH is a progressive disease that, if left untreated, leads to early mortality. It is characterized by changes in the pulmonary vasculature that eventually lead to strain on the right ventricle, right ventricular failure, and, ultimately, death. Endothelin, a potent vasoconstrictor, is responsible for these changes.[1] Increased endothelin concentrations have been found in the pulmonary vasculature and actually correlate with disease severity.[2]

Bosentan is the only oral nonselective endothelin receptor antagonist (ERA) available for the treatment of PAH. Efficacy of this drug in the treatment of PAH has been shown in clinical trials.[3,4] Studies have shown benefit with regard to exercise tolerance, hemodynamic function, and improved oxygenation.

In this study, Apostolopoulou and colleagues set out to show the effects of bosentan on patients with PAH secondary to CHD. Twenty-one patients, World Health Organization (WHO) functional class II-IV, with PAH secondary to CHD (either repaired or uncorrected defects) and a fixed pulmonary vascular resistance (PVR) participated in this study. No treatment changes were allowed 1 month before entry or during the trial other than the addition of bosentan. Patients were not on therapy with epoprostenol in this study. The clinical trial was an open-label, noncontrolled study. Complete hemodynamic studies were done before enrollment and at 16 weeks of therapy, with baseline mean pulmonary artery pressures (mPAP) of approximately 92 mm Hg and median PVR index of 2048. WHO functional class was also evaluated at that time. Twelve patients were WHO functional class III, 5 (age < 12 years old) were class II, and the rest were functional class IV. Seventy-one percent of the patients had resting saturations of < 95%.

After 16 weeks of therapy, 13 of the 21 patients had shown improvement by 1 functional class. Also demonstrated was an increase in peak oxygen consumption and exercise capacity with a 42-m increase in distance on 6-minute walk test. Increased saturations before completion of exercise were also noted in the cyanotic group, from 64% to 69%. Improvement in hemodynamics such as PVR index, mean right atrial pressure, and pulmonary to systemic blood flow ratio was noted. Two patients died during the study from suspected arrhythmias but had noted improvement in 6-minute walk distance before death as well as improvement in WHO functional class. At 1.3 years post study, the remaining patients were still on therapy and stable.ReferencesWort SJ, Woods M, Warner TD, et al. Endogenously released endothelin-1 from human pulmonary artery smooth muscle promotes cellular proliferation: relevance to pathogenesis of pulmonary hypertension and vascular remodeling. Am J Respir Cell Mol Biol. 2001;25:104-110.Allen SW, Chatfield BA, Koppenhafer SA, et al. Circulating immunoreactive endothelin-1 in children with pulmonary hypertension: association with acute hypoxic pulmonary vasoreactivity. Am Rev Respir Dis. 1993;148:519-522.Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study. Lancet. 2001;358:1119-1123.Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.

Abstract

Supported by an independent educational grant from Actelion.

This is a part of article Pulmonary Arterial Hypertension, November 2005 Taken from "Erectile Disfunction Treatment" Information Blog