Encouraging results of a randomised trial in this week’s issue of THE LANCET suggest that the drug bosentan could play an important future role in the treatment of pulmonary hypertension.
Pulmonary hypertension (raised pressure in the blood vessels supplying the lungs) causes thickening of the right ventricle of the heart and can be associated with chest pain and heart failure. Primary pulmonary hypertension is rare (affecting around 1 in 2 million people), but secondary disease is thought to affect tens of thousands of people every year. Treatment with conventional blood-pressure-lowering drugs is not effective. Endothelin 1, a powerful endogenous vasoconstrictor, is thought to be a possible cause of the disorder. Richard Channick and colleagues from the University of California San Diego, USA, investigated whether bosentan, a dual endothelin-receptor antagonist that can be taken orally, was effective in treating patients with severe pulmonary hypertension.
32 patients were randomly assigned either bosentan (62.5 mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. Patients given bosentan did better in a six-minute walking test at 12-week follow-up (average increase of 70 metres) compared with patients given placebo (average decrease of six metres). Treatment with bosentan substantially improved cardiopulmonary haemodynamics from baseline to week 12 compared with placebo: pulmonary vascular resistance fell substantially from baseline in patients given bosentan, and rose in those given placebo; treatment with bosentan decreased the average pulmonary artery pressure, the pulmonary capillary wedge pressure, and the average right-atrial pressure. All three measures increased in the placebo group.
Richard Channick comments: "Our results suggest that endothelin plays an important part in the pathogenesis and evolution of pulmonary hypertension. Oral use of a dual endothelin-receptor antagonist, such as bosentan, which blocks both ETA and ETB receptors, could be a new therapeutic approach for this disease."
In an accompanying Commentary (p 1113), Jocelyn Dupuis from the Montreal Heart Institute, Canada, concludes: "Future trials should help clinicians better define the place of these agents [endothelin-receptor antagonists] in the therapy of pulmonary hypertension. They should also be designed to answer other important issues, such as improvement in survival, and the role of these agents in class IV patients with or without concomitant epoprostenol therapy."
Contact: Kate Deely Smith, UCSD Health Sciences Communications, 200 West Arbor Drive, San Diego, CA 92103-8230 T) 1-619-543-6163; F) 1-619-543-5423 ; E) kdeely@ucsd.edu
Dr Jocelyn Dupuis, Montreal Heart Institute and University of Montreal, Montreal, Quebec H1T 1C8, Canada; T) 1-514-376-3330 ext. 3542 ; F) 1-514-376-1355 ; E) dupuisj@icm.umontreal.ca
Journal
The Lancet