5-year Survival Rate Lower in Congenital Heart Disease Patients With PAH

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The five-year survival rate is markedly reduced among adults with pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD), compared with other types of CHD, real-world data from the COMPERA-CHD registry show.

This worse mortality rate occurred despite the increasing number of PAH-targeted combination therapies now available for patients with congenital (since birth) defects, the researchers found.

The study, “Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry,” was published in the Journal of Clinical Medicine.

Congenital defects in the heart or in major blood vessels — collectively called congenital heart disease or CHD — can lead to the development of pulmonary hypertension (PH), a condition that aggravates the natural disease course and complicates recovery from surgery or other types of interventions needed for CHD treatment.

The nature of the congenital anomalies affects the prevalence and severity of PH, as well as its clinical outcomes. Yet, the impact of PH in CHD remains poorly studied.

Estimates suggest that the prevalence of PAH in people with congenital heart disease varies from 4.2% to 28%.

Although several therapies have been approved for PAH, data is still missing on their efficacy and safety among CHD patients. Moreover, real data on the outcomes of people with PAH and CHD is scarce compared with that available for those with idiopathic PAH, whose disease has no known cause.

The COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) registry (NCT01347216), launched in 2007, is a prospective, European-based registry for adults with all forms of PH, including those who have begun taking any vasoactive therapy. Altogether, patients are enrolled from 49 centers across 11 European countries.

In this new study, researchers analyzed the characteristics, treatments, and outcomes of a subgroup of patients in COMPERA who had PH due to CHD.

At the time of the analysis, about 8,200 people with various PH forms were registered in COMPERA; among them, 680 (8.3%) had PH caused by CHD. Of these, 320 (47.1%) had evidence of Eisenmenger syndrome, 167 (24.6%) had “non-Eisenmenger PAH,” and seven (1.0%) had Fontan circulation. The remaining 186 patients with CHD (27.4%) were not fully characterized due to incomplete data.

Of note, people with Eisenmenger syndrome are born with a defect known as a “hole in the heart” between the left and right pumping chambers. This condition causes blood to circulate abnormally, leading to increased pressure in the lungs’ arteries. A person with Fontan circulation is born with a single ventricular chamber in the heart, instead of two.

The median age of patients in the CHD group was 44 years, with a range in ages from 18 to 87, and the majority (66.6%) were women. More than half (379 patients, corresponding to 55.7%) were older than 30, while 148 (21.8%) were younger than age 30. A total of 153 (22.5%) people were age 60 or older.

Nearly two-thirds of the individuals — 167 or 63.3% — developed PAH after CHD reparative cardiac surgery, from a total of 264 surgeries.

The majority of CHD patients (600 or 88.2%) received targeted PAH therapy. Endothelin receptor antagonists or ERAs were given to 389 patients (65%); the most frequently used ERA was Actelion’s Tracleer (bosentan), given to 276 people. A total of 353 patients (59%) received a phosphodiesterase type-5 inhibitor (PDE-5), including Pfizer’s Revatio (sildenafil; given to 286 patients) or United TherapeuticsAdcirca (tadalafil; given to 67 people).

Less common medications included: prostanoids, received by 35 patients (5.8%); Adempas (riociguat), a vasodilator belonging to the class of soluble guanylate cyclase stimulators (used for 17 people, 2.8%); calcium channel blockers (24 patients, 4%); and a tyrosine kinase inhibitor (used in one patient).

All patients with Fontan circulation were treated with PDE-5 inhibitors.

In general, the first treatment of choice was to use a single therapy, or monotherapy, for most patients. In 33% of the Eisenmenger and 27% of the non-Eisenmenger groups, patients first started a combination treatment of at least two PAH medications. Over time, the number of individuals given a combination therapy increased significantly.

“While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%,” the researchers wrote.

The use of anticoagulants or platelet inhibitors varied among the CHD patients. Those with Eisenmenger used these therapies the least, while patients with Fontan circulation had the highest rates of anticoagulation medication use.

Survival rates were assessed among 511 patients with PAH-CHD and 1,326 with idiopathic PAH. The five-year survival rate was 78% for the CHD group and 66% for idiopathic PAH.

Among those receiving PAH-targeted therapy at the study’s start, 91 people with CHD and 419 idiopathic PAH patients died during the five-year follow-up. This corresponds to a survival rate of 76% for CHD and 54% for idiopathic PAH.

In the CHD group receiving targeted therapy, Eisenmenger patients had an estimated five-year survival of 78% and non-Eisenmenger-PAH patients had a 77% rate.

Taken together, “in COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH,” the researchers wrote.

Despite its better survival compared with idiopathic PAH,  people with PAH associated with CHD had a worse mortality rate compared with CHD patients without PAH, the researchers noted.

“In adults with PAH from CHD, all-cause mortality is more than two-fold, and the rate of health service utilization is three-fold higher compared with CHD without PAH,” they wrote.

The team emphasized that this occurs “despite an increasing number of patients on PAH-targeted combination therapy.”

Thus, “the results of this study imply that it must be ascertained in any case, that the particularities of CHD are taken into account in diagnosis and treatment, as the management of PAH-CHD is often different from other forms of PAH,” the researchers concluded.

“Accordingly, such patients should always be managed with cooperation between CHD specialists and PAH specialists, preferably in tertiary care settings,” they added.

A Conversation With Rare Disease Advocates