Patients with heart failure with preserved ejection fraction (HFpEF) and high blood pressure in the lungs (pulmonary hypertension) had significant improvements in blood pressure and vascular health after taking sotatercept, according to a study presented at the American College of Cardiology’s Annual Scientific Meeting (ACC.26).
Group 2 pulmonary hypertension is caused by abnormalities in the left side of the heart. This study is the first to test sotatercept in a specific subset of patients with Group 2 pulmonary hypertension, including HPpEF and severe combined post-precapillary pulmonary hypertension (CpcPH).
CpcPH occurs when high pressure caused by heart problems flows back into the lungs, damaging blood vessels in the lungs over time, making breathing difficult and limiting daily activities. HFpEF is a type of heart failure in which the left ventricle of the heart does not relax completely and may become stiff. This reduces the body’s ability to properly fill with blood between each heartbeat, causing a variety of symptoms such as fatigue, shortness of breath, and swelling.
Sotatercept is a first-in-class drug designed to inhibit the abnormal growth of cells in blood vessel walls. It is approved for Group 1 pulmonary hypertension, which affects the pulmonary arteries and can be caused by genes, toxins, and some systemic diseases. Although multiple therapies are available for the treatment of group 1 pulmonary hypertension, no drug to date, including CpcPH-HFpEF, has been proven effective for group 2 pulmonary hypertension.
Patients and the scientific community have long awaited an effective treatment for CpcPH associated with HFpEF, as previous trials have failed and there is no approved treatment. Although we have seen recent improvements in HFpEF treatment, none were specific to the distinct clinical condition of CpcPH-HFpEF. These patients still have severe heart failure symptoms. ”
Mardi Gomberg, MD, MSc, cardiologist and professor of medicine at the George Washington School of Medicine and Health Sciences in Washington, D.C., and lead author of the study
Researchers enrolled 164 patients with CpcPH-HFpEF in the phase 2 trial. The mean patient age was 75 years and 70% were female, reflecting the typical patient population of CpcPH-HFpEF. Participants were randomly assigned 1:1:1 to either 0.3 mg/kg sotatercept, 0.7 mg/kg sotatercept, or placebo. At week 24, researchers assessed hemodynamic and clinical outcome measures of pulmonary hypertension.
Sotatercept treatment improved pulmonary artery pressure and led to a statistically significant reduction in pulmonary vascular resistance, the primary endpoint. Pulmonary vascular resistance is a measure of how difficult it is for blood to flow through blood vessels in the lungs. When blood vessels in the lungs become narrowed, stiff, or damaged, the heart has to work harder to pump blood into the lungs. Higher resistance means the heart is working under more stress, so reduced pulmonary vascular resistance means less strain on the heart. Secondary endpoints were also favorable for those taking sotatercept, showing improvements in 6-minute walk distance and right heart function, as well as lower rates of clinical deterioration events.
“This is really interesting because we see improvements in clinical markers of heart failure and biomarkers of cardiac function on both the right and left sides,” Gomberg said. “Left atrial volume and left atrial pressure (measured as wedge pressure) improved, which are characteristics that can put you at risk for a variety of poor outcomes in HFpEF. To see these improvements on top of improvements in pulmonary vasculature is huge.”
Sotatercept demonstrated a favorable safety profile, with rates of adverse events comparable to those seen in previous clinical trials. Initial results suggest that low doses of sotatercept appear to optimize benefit and risk in this patient population.
It should also be noted that this study also included patients who had undergone a procedure to repair their heart valves at least one year before enrolling in the study. Although these patients represented only a small number of participants, the results revealed that this group experienced similar benefits from sotatercept without showing an increased risk.
As a phase 2 trial, this study was limited by the relatively small sample size. The 24-week placebo-controlled period also limits the ability to draw conclusions regarding long-term safety and efficacy. Based on the positive results obtained in the study, the researchers plan to proceed with a phase 3 study testing sotatercept in CpcPH-HFpEF.
The study was funded by Merck, the maker of sotatercept.
The study was published online at the same time. circulation At the time of the presentation.
Dr. Gomberg will present the study, “Efficacy and Safety of Sotatercept in Concomitant Postcapillary and Precapillary Pulmonary Hypertension Associated with Preserved Ejection Fraction Heart Failure: Results from the Phase 2 Cadence Study,” on Sunday, March 29 at 10:45 a.m. CT/15:45 p.m. UTC in the main tent of the Great Hall.
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American College of Cardiology
