Benefits of PADN surgery in CpcPH sustained for 3 years in trial

Better exercise capacity seen in patients with rare form of PH

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A one-time surgical procedure called pulmonary artery denervation or PADN was linked to a reduced risk of clinical worsening in the long term for people with combined pre- and post-capillary pulmonary hypertension (CpcPH).

That’s according to three-year data from a clinical trial involving CpcPH patients who underwent the procedure. Patients undergoing PADN also experienced greater gains in their ability to exercise and in heart function compared with individuals who had a sham surgery.

“PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes,” the researchers wrote.

The study, “3-Year Outcome in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension: Results From PADN-5 Trial,” was published in JACC: Heart Failure.

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Trial tests PADN in patients with pre- and post-capillary PH

CpcPH and postcapillary PH are two types of left heart disease-associated pulmonary hypertension, or LHD-PH. Both are associated with high pressure in the veins that fill the heart’s left atrium with oxygenated blood from the lungs.

However, CpcPH also shares certain characteristics with another class of PH known as pulmonary arterial hypertension (PAH). These conditions both show evidence of increased pulmonary vascular resistance (PVR), or a resistance to blood flow in the arteries carrying blood to the lungs from the heart.

While therapies exist to treat PAH, there are none approved for LHD-PH, including CpcPH. It has not been well established whether PAH medications would be of benefit for CpcPH; they are not currently recommended for this patient group.

It’s been proposed that one way leading to CpcPH is overactivity of mechanisms that cause vasoconstriction, or blood vessel narrowing.

As such, pulmonary artery denervation (PADN), a surgical technique to reduce activation of the nerves that control vasoconstriction, could be a promising therapeutic strategy for CpcPH patients.

This Phase 2 PADN-5 trial (NCT02220335) was designed to evaluate the safety and efficacy of the procedure among 98 adult CpcPH patients at four study sites.

Participants were randomly assigned to receive a single PADN procedure or a sham surgery. Those given the sham procedure also were assigned to take Revatio (sildenafil) — an approved PAH therapy — three times daily for six months. All participants could continue on any existing anti-heart failure medications.

The trial’s main goal was to evaluate changes in exercise capacity after these six months, as assessed by the distance a person can walk in six minutes, also called the 6MWD test.

This goal was met, with patients who underwent PADN seeing a 21.4% improvement in exercise capacity after six months. That compared with about 4.9% in the Revatio group.

PADN also was associated with significant improvements in blood flow or hemodynamic measurements and a reduction in clinical worsening or hospitalization rates compared with the Revatio group.

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Long-term data shows better outcomes with PADN

Now, scientists reported on three-year follow-up data from PADN-5 participants. After the trial’s initial six-month period, continuation of Revatio in the control group or initiation of other PAH therapies in any patient was left to the discretion of the individual physician.

The main goal here was to assess the occurrence of clinical worsening, defined as heart/lung-related deaths, rehospitalizations, or heart/lung transplants.

After three years, 34 of 50 patients (68%) in the sham group and 38 of 48 individuals (about 80%) in PADN group were alive.

The results showed that clinical worsening was reported in 50% of patients after three years, including 62% of the sham group and 37.5% of the PADN group.

The more than two times higher risk of clinical worsening in the sham group was largely driven by higher rates of rehospitalization in these patients (56.2%) relative to the PADN group (35.4%), according to the scientists.

By the end of the study, there had been 25 cardiopulmonary deaths, including 16 (32%) in the sham group and nine (18.8%) of the PADN group, a difference that was not statistically significant.

Moreover, two people in the sham group had undergone a heart/lung transplant during follow-up.

Participants who underwent PADN continued to see greater improvements in exercise capacity and reductions in NT-proBNP, a marker of heart failure, compared with the sham group after three years.

In final statistical analyses, baseline 6WMD of less than 350 meters was associated with a risk of clinical worsening after three years, whereas PADN was associated with a reduced risk of worsening.

Findings overall demonstrate “the long-term benefits of PADN for patients with CpcPH,” the researchers wrote.

“We found that PADN led to a significant reduction in clinical worsening through the 3-year follow-up, mainly attributable to an extreme reduction in rehospitalization, in line with the significant improvements in exercise capacity and reduction in [cardiac parameters],” the team wrote.

The scientists noted that use of Revatio in the trial could potentially have influenced the results. This was particularly an issue since use of the therapy in the main trial meant some patients had to stop using certain heart failure medications.

However, since most patients were not using Revatio or other PAH medications after the initial six-month trial, the three-year findings are more likely directly related to the long-term effects of PADN, according to the scientists.

“Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH,” the team noted.

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