Comment by Jason Lazar, MD, FCCP
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050