People with severe pulmonary arterial hypertension (PAH) who respond strongly to early treatment with prostacyclin infusions may eventually be able to reduce or discontinue the therapy while maintaining long-term improvements, according to a study.
In a long-term analysis of 101 patients with severe PAH, about one in five improved enough to gradually stop prostacyclin infusions. Improvements in heart function and blood flow through the lungs were sustained for more than five years after treatment was discontinued.
“These hypothesis-generating findings suggest that an early and intensive treatment strategy may facilitate [blood flow] recovery and subsequent de-escalation in selected patients,” the researchers wrote.
The study, “Early parenteral prostacyclin therapy enables near-normal haemodynamics and treatment de-escalation in patients with haemodynamically severe pulmonary arterial hypertension,” was published in the European Respiratory Journal.
Prostacyclin infusions used to treat severe PAH
PAH is a form of pulmonary hypertension, a group of disorders characterized by high blood pressure in the pulmonary arteries, the blood vessels that carry blood from the heart to the lungs.
In PAH, these arteries become narrowed, restricting blood flow through the lungs and forcing the right side of the heart to work harder to pump blood.
People with severe PAH may be treated with infusions of lab-made prostacyclin, a naturally occurring molecule that helps widen blood vessels and improve blood flow. Prostacyclin therapies include treprostinil, sold as Remodulin and available in generic forms, and epoprostenol, marketed as Flolan and Veletri, as well as generics.
Researchers in Japan reviewed the medical records of 101 people with severe PAH who began prostacyclin infusions at a single center between 1999 and 2023. Their mean age was 34.1, and 82% were women.
Patients were started on prostacyclin infusions if they had a mean pulmonary arterial pressure (mPAP) of at least 50 mmHg, had not responded adequately to oral PAH medications, or had severe symptoms that substantially limited daily activities.
Nearly half (46.5%) had idiopathic PAH, meaning there was no identifiable cause. Other patients had PAH associated with connective tissue disease, heritable PAH, or heart disease. Ten women had postpartum pulmonary hypertension, which developed after childbirth.
The median time between a patient’s first physician visit and the start of prostacyclin treatment was 15 months.
About one in five patients able to reduce treatment
The patients had severe disease when they began prostacyclin therapy. Their median mPAP was 55 mmHg, and pulmonary vascular resistance — a measure of how difficult it is for blood to flow through the lungs — was also elevated.
Their median cardiac index, which measures the amount of blood pumped by the heart relative to body surface area, was 2.4 L/min per square meter.
During follow-up, 22% of patients improved enough to begin gradually reducing their prostacyclin dose. To qualify for treatment de-escalation, patients had to achieve near-normal blood flow measurements, including an mPAP below 25 mmHg and a cardiac index above 2.2 L/min per square meter.
Dose reductions began after an average of 4.1 years of prostacyclin treatment. Patients who successfully de-escalated therapy completely discontinued their infusions after an average of 7.7 years, with no adverse events associated with stopping treatment.
Several characteristics distinguished patients who were able to discontinue prostacyclin from those who were not.
Patients who stopped treatment were more likely to have developed PAH within six months after childbirth (31.8% vs. 3.8%). They also started prostacyclin infusions substantially sooner after their first physician visit — an average of 2.4 months compared with 28.7 months among those who did not discontinue therapy.
They also required lower maximum prostacyclin doses, at 52 nanograms/kg/min compared with 90 nanograms/kg/min.
“These observations suggest that early diagnosis and timely initiation of intensive therapy may facilitate [blood flow] recovery, thereby enabling subsequent treatment [reduction],” the researchers wrote.
Improvements maintained years after stopping infusions
The improvements achieved with prostacyclin therapy were generally sustained over long-term follow-up.
At an average of 5.1 years after stopping prostacyclin infusions, 64% of patients who discontinued treatment had normal pulmonary arterial pressure, defined as an mPAP below 21 mmHg. None of these patients died or required a lung transplant after stopping the infusions.
Importantly, discontinuing prostacyclin did not mean stopping PAH treatment altogether. Most patients who successfully came off the infusions continued taking combinations of oral PAH medications.
The researchers said this indicates that prostacyclin de-escalation occurred “within the context of sustained multidrug therapy,” rather than representing complete treatment discontinuation.
Overall, the findings suggest that a subset of people with severe PAH may achieve substantial and lasting improvements after early, intensive prostacyclin treatment. However, the results come from a retrospective analysis at a single center and should not be interpreted to mean that prostacyclin infusions can be safely stopped without careful medical assessment and continued PAH therapy.