Early PAH treatment combo seen to improve blood flow, exercise ability
Study tested therapy sequence in 50 patients within 4 weeks of diagnosis
After a diagnosis of pulmonary arterial hypertension (PAH), rapidly starting treatment with a combination of therapies — both an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i) — can lead to notable short-term improvements in heart health and physical function.
That’s according to a new study, “Impact of rapid sequential combination therapy on distinct haemodynamic measures in newly diagnosed pulmonary arterial hypertension,” which was published in ESC Heart Failure.
PAH is characterized by increased pressure in the vessels that carry blood from the heart to the lungs. It’s recommended that most patients with PAH should be treated with both an ERA and a PDE5i, two classes of medication that can help reduce pulmonary blood pressure. This is because clinical trials trials have shown that combination treatment with medications that target different biological pathways improves clinical outcomes.
In this study, the scientists evaluated clinical and functional changes in 50 people who started on treatment with both an ERA and a PDE5i within four weeks, or about one month, of being diagnosed with PAH. The results showed that, after starting the combo PAH treatment, there were marked improvements in measures of blood flow and heart health.
“The magnitude of changes … reached upon initiation of rapid sequential combination therapy in the patients reported herein appear of major clinical relevance,” the researchers wrote.
Patients able to walk much further in test at 6 months and 1 year
The patients in this study specifically were treated with ERAs that included either Opsumit (macitentan) or Letairis (ambrisentan), and also with PDE5is like Revatio (sildenafil) and Adcirca (tadalafil), or with Adempas (riociguat), which is in a class of meds called soluble guanylate cyclase stimulators, or sGC-S.
All of them underwent assessments including right heart catheterization — a procedure used to measure pressure in the pulmonary blood vessels — both at the time of PAH diagnosis, and then again about half a year after starting treatment.
The results showed that, following the start of therapy, there were marked improvements in measures of blood flow and heart health. For example, mean mean pulmonary artery pressure (mPAP) decreased from 52.2 to 39 mmHg, reflecting less pressure in the main vessel that carries blood to the lungs. Pulmonary vascular resistance, a measure of how difficult it is to push blood through the lungs’ vessels, also decreased, from an average of 12.1 to 5.8 Wood units.
Treatment also led to marked decreases in levels of NTproBNP, a marker of heart damage.
Our data [show] that rapid sequential combination therapy with ERA and PDE5i/sGC-S initiated in patients with newly diagnosed PAH substantially improves multiple prognostically relevant pulmonary [blood flow measures] … at early follow-up.
Imaging of the heart suggested slight reductions in the size of the right side of the heart after a heartbeat — in PAH, this part of the heart typically becomes enlarged because it’s put under abnormal strain trying to pump blood to the lungs.
“Our data [show] that rapid sequential combination therapy with ERA and PDE5i/sGC-S initiated in patients with newly diagnosed PAH substantially improves multiple prognostically relevant pulmonary [blood flow measures] … at early follow-up,” the researchers wrote.
The patients also saw improvements in physical function after starting these treatments. The average distance these individuals could walk in six minutes, which is a common measure of exercise ability, increased by nearly 50 meters, or more than 160 feet, at six months after starting treatment, and was even higher at one year.
Taking all these changes collectively, the researchers calculated standardized PAH risk scores both before and a few months after starting treatment. The results broadly indicated that, based on these scores, patients had lower risk of serious PAH complications after starting on treatment, with more than half of patients deemed “low risk.”
“In our series, [blood flow] improvement upon initiation of rapid sequential combination therapy was associated with considerable improvement of patients’ risk status,” the researchers wrote.
The scientists noted that improvements tended to be more dramatic among younger patients who didn’t have as many co-occurring health problems, called comorbidities. But even for older patients, likely those with coexisting conditions, there were notable improvements seen for most cases with treatment.
Treatment with ERA and PDE5i was generally well tolerated in this study. The main side effects reported included headache, nasal congestion, and flushing, which are known to occur with this type of treatment combo.