PAH-Specific Therapies Benefit PAH Patients with Congenital Heart Disease, Review Study Shows

Vijaya Iyer, PhD avatar

by Vijaya Iyer, PhD |

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Clinical trials testing pulmonary arterial hypertension (PAH) therapies show that PAH patients who also have congenital heart disease (CHD) can also benefit from these therapies, improving exercise capacity, blood flow, and quality of life, a review study reports.

The study, “Pulmonary Arterial Hypertension Medical Management of the Adult Patient with Congenital Heart Disease,” was published in the journal Cardiovascular Innovations and Applications.

PAH is caused by increased pressure in vessels that carry blood to the lungs. One PAH subtype is congenital heart disease-associated PAH (CHD-PAH), with congenital referring to a condition present at birth. It is estimated that approximately 5 to 10 percent of adult CHD patients will develop PAH.

CHD-PAH is linked to an increased risk of complications, and there is limited evidence about the impact of PAH-specific therapies for the treatment of CHD-PAH patients.

To address this question, researchers conducted a review study on published research data about the potential benefits of PAH-specific therapies for CHD-PAH patients.

Researchers found that in several, small studies, CHD-PAH patients treated with PAH therapies had improved cardiovascular blood flow and exercise capacity, as well as a reduction in functional class — where the lower the class, the less severe the disease symptoms.

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In the Phase 3 SUPER-1 clinical trial (NCT00644605), treatment with Revatio (sildenafil), marketed by Pfizer, resulted in improved exercise capacity and blood flow after 12 weeks of therapy in a group of adult patients with PAH, CHD-PAH, or PAH associated with connective tissue disease. However, specific data on the CHD-PAH subgroup was not available.

A similar result was also seen in other trials, including those testing Adcirca (tadalafila), marketed by United Therapeutics, but again, CHD-specific outcomes were not available, although there was an overall improvement in the general PAH patient groups taking the therapy.

The Phase 3 SERAPHIN trial (NCT00660179), testing Actelion’s Opsumit (macitentan) in PAH patients included 8.4% CHD-PAH patients. Results showed reduced disease and death in patients receiving Opsumit.

Eisenmenger syndrome, most often characterized by a hole in the heart, is a type of CHD-PAH. In the Phase 4 BREATH-5 trial (NCT00367770), Tracleer (bosentan), marketed by Actelion, improved exercise capacity and blood flow in CHD-PAH patients, regardless of the location of the heart defect.

Similar results were found in trials testing other PAH-specific therapies. The combination of two or more PAH treatments, given either together or subsequently, also showed positive outcomes in CHD-PAH patients, researchers reported.

The team also highlighted the “treat-to-close” strategy in PAH patients, which involves surgery to close a hole in the heart, such as what occurs in Eisenmenger syndrome. A 2016 study showed that the use of PAH-specific therapies before the surgery resulted in significant symptomatic relief, with no complications or adverse events.

“PAH-targeted pharmacotherapy may be used to optimize cardiopulmonary hemodynamics so as to improve patients’ operability in repairing the cardiac defect,” the researchers wrote.

However, they also noted that “the CHD-associated PAH population is largely underrepresented within PAH pharmacotherapy clinical trials, thus making it difficult to extrapolate general PAH results to all patients with CHD-associated PAH.”

Limited data aside, the team concluded that “in patients with CHD-associated PAH, PAH-specific therapy appears to be an effective method in increasing functional capacity, reducing functional class, and producing more favorable pulmonary vascular hemodynamics. Multiple modalities of therapies appear to be effective in treatment.”