Bosentan reduces decline of patients with early stage pulmonary arterial hypertension (early study)

June 19, 2008

Patients in the early stages of pulmonary arterial hypertension (PAH) treated with the drug bosentan show reduced clinical decline compared with patients given placebo, and thus the drug could be beneficial in this group of patients. These are the conclusions of authors of an Article published in this week's edition of The Lancet.

PAH is a devastating, progressive disease with increasingly debilitating symptoms. The idiopathic form of the condition (ie, with no underlying cause) affects mainly young women but it can be associated with many other diseases in patients of both sexes and all ages. The resulting increased pulmonary vascular resistance in the lungs leads to structural damage to the heart, limiting patients' exercise capacity, and eventually, leads to heart failure and death. The protein endothelin plays a key role in PAH by binding to two receptor sites in the vascular smooth muscle cells in the lungs -- the endothelin A and B receptors. Bosentan is an orally active dual endothelin receptor antagonist, which means it competes with endothelin at both A and B receptor sites. Studies have shown that bosentan improves exercise capacity and pulmonary vascular resistance (PVR), and slows clinical decline; but these studies have focused mainly on patients with the later stages of the disease, ie, WHO functional classes III and IV. Professor Nazzareno Galiè, Institute of Cardiology, University of Bologna, Italy, and colleagues did a randomised controlled trial to assess the effects of bosentan on patients with earlier stage PAH, ie, WHO functional class II.

The trial enrolled 185 PAH patients aged 12 years or over with PAH, of whom 93 were randomised to received bosentan and 92 to placebo. The PVR of each patient was measured by right heart catheterisation*, and also the distance walked in six minutes at the start of the trial. Measurements were taken at the start of the trial (baseline) and at six months. Analyses were done with 168 patients: 80 bosentan, 88 placebo for PVR; and 177 (86 bosentan, 91 placebo) for 6 minute walk distance.

The researchers found that after six months, the mean PVR was 83.2% of baseline in the bosentan group and 107.5% in the placebo group --giving a statistically significant treatment effect of -22.6% for the bosentan patients. Mean 6 minute walk distance increased 11.2m in the bosentan group from 438m at baseline to 449m, while in the placebo group the walk distance decreased from 431m at baseline to 423m; however, the changes in walk distance were not statistically significant. Fewer bosentan-treated patients (3%) experienced clinical worsening events (death, hospitalisation, and symptomatic progression of PAH) than in the placebo group (14%) -- this finding was statistically significant. A total of 12 (13%) patients in the bosentan group and eight (9%) in the placebo group reported serious adverse events, the most common of which were fainting in the bosentan group and right ventricular failure in the placebo group.

The authors conclude: "The EARLY study shows that, if left untreated, mildly symptomatic pulmonary arterial hypertension can progressively deteriorate both clinically and in terms of pulmonary vascular resistance, despite the maintenance of exercise capacity. Bosentan treatment in this patient population is associated with improvements in pulmonary vascular resistance and prevention of clinical deterioration. These findings indicate that treatment with bosentan might be of benefit to patients with WHO FC II pulmonary arterial hypertension."

In an accompanying Comment, Dr Neeraj Dhaun and Professor David Webb, Queen's Medical Research Institute, University of Edinburgh, UK, say: "This study broadens the potential for bosentan as a treatment in pulmonary arterial hypertension, and the evidence presented by Galiè and colleagues should soon be translated into clinical practice. The scope of endothelin-receptor antagonism as a treatment option continues to extend beyond pulmonary arterial hypertension and includes chronic kidney disease, diastolic heart failure, resistant hypertension, and cancer."
Notes to editors: *right heart catheterisation: the insertion of a small catheter through a peripheral vein into the pulmonary artery.

Professor Nazzareno Galiè, Institute of Cardiology, University of Bologna, Italy T) +39-338-6721805 E)

Dr Neeraj Dhaun and Professor David Webb, Queen's Medical Research Institute, University of Edinburgh, UK T) + 44 (0) 131 242 9210 E)


Related Heart Failure Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Machining the heart: New predictor for helping to beat chronic heart failure
Researchers from Kanazawa University have used machine learning to predict which classes of chronic heart failure patients are most likely to experience heart failure death, and which are most likely to develop an arrhythmic death or sudden cardiac death.

Heart attacks, heart failure, stroke: COVID-19's dangerous cardiovascular complications
A new guide from emergency medicine doctors details the potentially deadly cardiovascular complications COVID-19 can cause.

Autoimmunity-associated heart dilation tied to heart-failure risk in type 1 diabetes
In people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population

Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.

Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.

Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.

How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.

Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.

Read More: Heart Failure News and Heart Failure Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to