Aug. 8, 2025
Caution on a Hypertension Drug
Despite enthusiasm around the potential benefits of the drug sotatercept for patients with pulmonary hypertension, Pitt experts and colleagues observed a significant rate of new or worsening pericardial effusions in PAH patients treated with it.
TOPICS: Chronic Disease | Research
Designs on Aging-Ready
By Strategic Communications
Back in 1995, when Stephen Chan, Vitalant Professor of Vascular Medicine and professor of medicine (Division of Cardiology) at the University of Pittsburgh, was a medical student, pulmonary arterial hypertension (PAH) was a death sentence—100% of patients died within two years of their diagnosis. Now, 30 years later, there are more than 20 approved drugs for PAH that can improve symptoms and increased the survival rate to 50% within five to seven years of a diagnosis. Unfortunately, there is still no cure for PAH.
Following the 2024 Food and Drug Administration approval of sotatercept, a drug that showed dramatic improvements in shortness of breath and pressures in the lungs and heart in patients with an inherited form of PAH, there was a sense of increased promise for treating PAH and achieving a cure.
However, caution may still lie in that promise.
In a research letter, published on Aug. 8, 2025, in the European Respiratory Journal, Stephen Y. Chan—also director of the UPMC Comprehensive Pulmonary Hypertension (PH) Program and of the Vascular Medicine Institute—along with colleagues from five other U.S. PH centers of excellence, reported a significant rate of new or worsening pericardial effusions in PAH patients treated with sotatercept.
This Q&A has been lightly edited.
“This evolving clinical scenario calls for heightened vigilance for how we use this drug as well as for timely intervention from treating clinicians.”
Stephen Chan, Vitalant Professor of Vascular Medicine
Q: What is sotatercept and how does it work?
SC: Sotatercept works by inhibiting a pathway (activin signaling) that controls an inherited form of PAH. Some believe this is the first “disease-modifying” drug for pulmonary hypertension and is a “game-changer” in the treatment of PAH and the quest for a cure.
Q: What did you learn from your research that led to this research letter?
SC: While some side effects were found in the clinical trials leading to sotatercept approval, other important side effects are now being recognized as associated with the use of this drug, such as GI bleeding, skin lesions and aberrant blood vessel formation that causes worsened oxygen levels. However, one important condition that, to a large extent, was not observed in the sotatercept clinical trials was the development of new or worsening pericardial effusion (collection of fluid around the heart). When that fluid accumulates, it can compromise heart function and reduce the ability of the heart to pump blood around the body. Untreated pericardial effusion, when large enough, can lead to hemodynamic collapse and major complications and even death.
Q: What were the findings that were reported?
SC: Namely, in more than 400 PAH adults who were consecutively treated with sotatercept as add-on therapy at six comprehensive care centers in the South, Midwest and Northeast United States, approximately 5% of these patients developed new or worsening pericardial effusions, some of whom had to undergo surgical drainage procedures. Historically, this is a much higher rate of effusions than what we have seen in our PAH patients, with more severe consequences.
Q: How will this report help patients?
SC: These findings are directly important to PAH patients being treated or considering treatment with sotatercept. We are very enthusiastic about the positive benefits that sotatercept could bring to our patients. But, this evolving clinical scenario calls for heightened vigilance for how we use this drug as well as for timely intervention from treating clinicians. Further research will be essential to determine if this drug is directly responsible for these pericardial effusions and to better define the mechanism and risk factors for this condition.