The dual endothelin receptor antagonist caused early fluid retention.
A recent study found that a dual endothelin receptor antagonist creates early fluid retention in patients with severe chronic heart failure.
Bosentan, a receptor antagonist used to treat pulmonary artery hypertension, was tested for its long-term effect on severe chronic heart failure patients’ morbidity and mortality in a double-blind trial study led by Dr. Milton Packer (pictured), distinguished scholar in Cardiovascular Science at Baylor University Medical Center.
Researchers sought to provide a long-term trial to better understand an endothelin receptor antagonist’s role in combating endothelin-1 (ET-1). ET-1 has been linked to various cardiovascular conditions, such as heart failure, systemic and pulmonary hypertension, and renal failure.
Bosentan was the endothelin receptor subtypes A and B blocker approved by the Food and Drug Administration. It is used commonly to treat pulmonary arterial hypertension (PAH). The research study noted that endothelin receptor antagonists have had “disappointing results” in short-term clinical trials involving heart failure patients.
Using 2 identical double-blind trials and 1,613 New Yok Heart Association functional class III-B to IV heart failure patients, researchers conducted a study of bosentan’s role. Patients were assigned at random to receive either a twice-daily 125mg dose of bosentan or placebo for a median of 18 months.
The primary outcome for each trial was clinical status at 9 months — as assessed by the hierarchical clinical composite – and the outcome across the 2 trials was death, or hospitalization for heart failure, according to the study.
Bosentan did not influence clinical status at 9 months in either trial, and 633 patients died or were hospitalized for heart failure — 49% being bosentan patients.
The treatment patients also reported a stronger rate of fluid retention in the trial’s first 2-4 weeks, according to the study. This was proven in patients’ increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure — despite intensified background diuretics.
The study actually reported a slightly greater percentage of placebo patients without heart failure related event than bosentan patients through the first year of the trial, before leveling out and falling just beneath the bosentan patient percentage by week 117. Both patient groups reported a steady decline in percentage of patients without an event over the entire trial.
During the study’s follow-up phase, 173 patients died in the placebo group and 160 died in the bosetan group. Though 10% of the bosentan group showed “meaningful increases” in hepatic transaminases, no patients suffered acute or chronic liver failure.
The study concluded that bosentan does not improve severe chronic heart failure patients’ clinical courses or natural history, but caused “early and important” fluid retention.
The study, “Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure,” was published in a May issue of the Journal of American College of Cardiology.