Early treatment may let PAH patients scale back infusions over time
People with severe PAH who respond to early prostacyclin maintain benefits
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People with severe pulmonary arterial hypertension (PAH) who respond well to early treatment with prostacyclin infusions may be able to reduce or stop the treatment, a study suggested.
In a long-term analysis of 101 patients, about one in five achieved enough improvement in heart and lung blood flow measurements to gradually discontinue this therapy, with benefits maintained for more than five years.
“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.
PAH is a form of pulmonary hypertension, a group of diseases marked by high blood pressure (hypertension) in the pulmonary arteries that supply blood to the lungs. PAH is caused by the narrowing of the pulmonary arteries, which restricts blood flow and makes the right side of the heart work harder to pump blood.
Study analyzes medical records
Severe PAH treatment may involve infusions of lab-made prostacyclin, a naturally occurring molecule that widens blood vessels. This may include treprostinil (sold as Remodulin, with generics available) and epoprostenol (sold as Flolan and Veletri, in addition to generics).
Researchers in Japan analyzed the medical records of patients with severe PAH (mean age 34.1, 82% women) who started prostacyclin infusions at a single center between 1999 and 2023. Patients received the treatment if they had a mean pulmonary arterial pressure (mPAP) of at least 50 mmHg, did not respond adequately to oral PAH medications, or had severe symptoms that substantially limited their daily activities.
Nearly half of the participants (46.5%) had idiopathic PAH, meaning the disease had no known cause. Other forms included PAH associated with connective tissue diseases, heritable PAH, and heart disease-associated PAH. Ten women had postpartum (after childbirth) pulmonary hypertension. The median time from the first physician visit to starting prostacyclin infusions was 15 months.
The patients had severe disease when they started treatment, with a median mPAP of 55 mmHg. They also had elevated pulmonary vascular resistance — which measures how difficult it is for blood to flow through the lungs — and a median cardiac index (a measure of the volume of blood pumped by the heart divided by body surface area) of 2.4 L/min per square meter.
Twenty-two percent of patients improved enough to begin gradually reducing their prostacyclin infusions. To be eligible, they had to achieve nearly normal blood flow measurements, including an mPAP lower than 25 mmHg and a cardiac index higher than 2.2 L/min per square meter.
Dose reduction began after a mean of 4.1 years of treatment, and patients stopped prostacyclin infusions completely after a mean of 7.7 years, without adverse events.
Patients who successfully discontinued prostacyclin differed from those who did not. They were more likely to have developed PAH within six months of childbirth (31.8% vs. 3.8%), started parenteral infusions sooner after their first visit (2.4 months vs. 28.7 months), and required lower maximum doses of the therapy (52 nanograms/kg/min vs. 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 in blood flow measurements were maintained during long-term follow-up. At a mean of 5.1 years after stopping the treatment, nearly two-thirds (64%) of patients had normal pulmonary arterial pressure, defined as an mPAP lower than 21 mmHg. None died or required a lung transplant after stopping prostacyclin infusions.
The researchers noted that patients who successfully stopped these infusions generally remained on combinations of oral PAH medications, “indicating that [reduction] occurred within the context of sustained multidrug therapy” rather than complete treatment discontinuation.
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