Winrevair, prostacyclin therapies work differently to improve PAH outcomes
New study finds 2 treatments have different effects on blood flow
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While both Winrevair (sotatercept) and prostacyclin therapies are used to treat pulmonary arterial hypertension (PAH), a new study shows the two treatments appear to affect blood flow differently among PAH patients.
When people with this rare type of pulmonary hypertension started prostacyclin treatment, resistance to blood flow in the lungs fell, and the heart pumped out more blood. After Winrevair was added, pressure in the lungs continued to fall without substantially increasing the heart’s pumping output, data showed.
The findings don’t suggest that one treatment is better than another in PAH, but rather indicate that they may work differently to improve patient outcomes, according to the researchers.
“Both treatments decreased [pulmonary vascular resistance (PVR)] through different mechanisms,” the team wrote. PVR is a measure of how hard the right side of the heart must work to push blood through the lungs, and indicates PAH severity.
The study, “Haemodynamic Responses to Sotatercept and Parenteral Prostacyclins in Pulmonary Arterial Hypertension Patients,” was published in The Journal of Heart and Lung Transplantation by researchers in Europe.
In PAH, the pulmonary arteries that carry blood from the heart to the lungs become narrowed, and the pressure in them rises. The right side of the heart, which must work harder to pump blood through these narrowed vessels, can become weakened and eventually fail.
Understanding the underlying mechanisms of PAH treatments
Treatments for PAH work in different ways to lower pulmonary artery pressure and reduce PVR.
When the heart has an easier time moving blood, it may be able to pump more out to the body. In clinical testing, that’s reflected by an increase in cardiac index (CI) and stroke volume index (SVI).
Most PAH therapies are associated with improvements in PVR, CI, and SVI. However, Merck‘s Winrevair has been found to improve PVR without clearly impacting CI or SVI.
According to the authors, it’s important to better understand those dynamics because CI and SVI are predictors of mortality in PAH.
To learn more, a team led by researchers from the Université Paris-Saclay School of Medicine in France examined changes in these measures among 62 adults with PAH in the country who received Winrevair as part of an early access program. At the study’s start, all were on stable regimens of standard PAH therapies, including an injectable prostacyclin therapy such as Flolan, Veletri, or Remodulin.
PVR, CI, and SVI were tracked with right heart catheterization, a standard test used to diagnose and monitor PAH. Measurements were taken before prostacyclin therapy was started, after prostacyclin therapy, and again after Winrevair was added.
Both Winrevair, prostacyclin therapy shown to benefit patients
The data showed that, as expected, prostacyclin therapy lowered pulmonary artery pressure and PVR, while CI and SVI increased. Put simply, prostacyclins reduced the pressure load on the lungs and helped the heart pump more blood.
When Winrevair was added, pulmonary artery pressure and PVR continued to drop. However, CI decreased slightly, and SVI remained unchanged. In other words, Winrevair further lowered lung pressure and resistance, but it didn’t substantially increase the amount of blood the heart pumped.
According to the authors, there are two possible explanations, namely, “the absence of CI increase with [Winrevair] may reflect either a distinct pharmacological effect compared to prostacyclins or a ceiling effect.”
The ceiling effect refers to the fact that, by the time Winrevair was started, prostacyclin treatment had already nearly normalized the amount of blood the heart was pumping for many patients, leaving little room for further improvement with second medication.
Another possibility, however, is that the medications simply work differently to be of benefit, according to the researchers. Specifically, Winrevair might improve circulation and oxygen delivery in ways that don’t show up as a higher CI or SVI.
For example, data suggest that Winrevair increases concentrations of hemoglobin, the protein on red blood cells that helps them carry oxygen. This could be one way the medication further improves patients’ functional abilities without increasing how much blood the heart pumps, according to the researchers.
The team also noted that changes in exercise capacity with Winrevair were not correlated with changes in CI or SVI.
“To our knowledge, this is the first description of haemodynamic evolution in a [group] of patients … treated with parenteral prostacyclins … followed by [Winrevair],” the scientists wrote.
The team added, however, that “further studies are needed to confirm our findings,” noting that their work focused on a fairly small group of people with relatively severe disease and “may not be generalizable to other [populations] of PAH.”
