A group of international pulmonary medical specialists have conducted a clinical trial to assess improvement in hospital based outcomes in patients with pulmonary arterial hypertension (PAH) when treated with macitentan, an endothelin receptor antagonist. The study team, led by Dr. Nazzareno Galiè, MD, head of the Pulmonary Hypertension Center at the Institute of Cardiology, Associate Professor of Cardiology, University of Bologna, published their findings in the latest edition of Heart Failure, a journal of the American College of Cardiologists.

Background Terminology:

• Endothelium: a layer of cells that line the heart and blood vessels.
• Endothelin: a molecule made by endothelium cells that constricts blood vessels and increases blood pressure.
• Endothelin receptor antagonist: drugs that limit the amount of endothelia produced in an effort to decrease high blood pressure.

About PAH

PAH, also known as pulmonary hypertension, defines a group of debilitating idiopathic (of unknown origin) or co-morbid conditions that cause breathlessness, loss of exercise capacity, and death due to elevated pulmonary artery pressure and subsequent right heart failure. It is a rare condition affecting 1 to 2 individuals for every 1 million in the US and Europe.  According to the CDC, PAH is more common among women, non-Hispanic blacks, and individuals 75 years or older.

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PAH is characterized by high blood pressure (BP) in the pulmonary arteries, which carry oxygen and blood from the heart to the lungs.  In healthy individuals, pulmonary arterial pressure should be approximately 25/10 millimeters of mercury (mmHg); for patients diagnosed with PAH this pressure consistently exceeds 40/20 mmHg. This elevated arterial pressure causes the right ventricle of the heart, which supplies blood to the pulmonary arteries, to pump ineffectively. This results in the right side of the heart working harder to pump blood around the body, leading to the condition’s debilitating effects and the eventual pre-mature death of the patient.

PAH and Endothelin Receptor Antagonists

In PAH there is a higher than normal concentration of endothelin found in the patient’s lungs that contributes to the increase in pulmonary arterial blood pressure. The endothelia receptor antagonists are used to decrease the concentration of endothelin, which leads to a decrease in a patient’s PAH symptoms.

The SERAPHIN Clinical Trial

This was a multi-center study that investigated the effects of macitentan on the risk, rate, and number of hospital days for both PAH-related and non-PAH related hospitalizations in comparison to a placebo. 742 patients who met the study criteria were randomly split into 3 different research groups as follows:

1. 250 received placebo.
2. 250 received 3 mg of macitentan.
3. 242 received 10 mg of macitentan.

The results showed that between the 2 treatment groups there were no differences found in the risk of being hospitalized for anything not related to PAH, but there were numerous important differences observed among the 2 groups that included:

• The risk for being admitted to the hospital for any reason was reduced by 18.9% in the macitentan 3mg group and 32.3% in the macitentan 10mg.
• The rates for being admitted to the hospital were reduced by 20.5% in the macitentan 3mg group and 33.1% in the macitentan 10mg.
• The number of days a patient stayed in the hospital after being admitted were reduced by 6% in the macitentan 3mg group and 31.0% in the macitentan 10mg group.
• The risk for being hospitalized for a reason related to PAH were reduced by 42.7% in the macitentan 3mg group and 51.6% in the macitentan 10mg group.
• The rate for being hospitalized for a reason related to PAH were reduced by 44.5% in the macitentan 3mg group and 49.8% in the macitentan 10mg.
• The number of days a patient stayed in the hospital after being admitted for a reason related to PAH were reduced by 53.3% in the macitentan 3mg group and 52.3% in the macitentan 10mg.

In response to the study’s findings the investigators stated, “Importantly, the reduction in PAH-related hospitalization was not offset by an increase in hospitalization for other causes. Overall, these findings provide further evidence of improved long-term outcomes in PAH patients treated with macitentan.”