In patients with a recent diagnosis of pulmonary arterial hypertension (PAH), the incorporation of the patient’s functional class, 6-minute walking distance, N-terminal fragment of pro-brain natriuretic peptide levels into risk stratification tools and multicomponent endpoints improved the ability of these tools and endpoints to predict mortality. These were among study results published recently in The Journal of Heart and Lung Transplantation.

Prognosis measures for PAH have continually evolved over the past 2 decades and continue to do so. Recently, trials of PAH have used a delay in clinical worsening as their endpoint instead of the previous endpoint of improvement in 6-minute walking distance, a measure set aside after demonstrating limited prognostic value, the study authors noted. However, they further noted that delayed worsening, as an endpoint for studying PAH, provides an incomplete picture because it does not capture clinical improvement. To overcome this problem, novel, multicomponent endpoints and risk stratification tools have been introduced for measuring PAH.

The current study sought to assess the prognostic value of certain novel, improved PAH endpoints and risk stratification tools. Toward that end, researchers analyzed the prognostic value of enhancing multicomponent improvement endpoints and established risk stratification tools by incorporating consideration of measures that included functional class (FC), 6-minute walking distance (6MWD), and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP).


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Investigators for the current retrospective study used the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) database (ClinicalTrials.gov Identifier: NCT01347216) to evaluate the prognostic value of adding assessments of functional class (FC), 6-minute walking distance (6MWD), and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) to previously used PAH endpoints and risk stratification tools. The current study involved a cohort of 596 patients newly diagnosed with PAH between January 2009 and December 2020 who were treatment-naïve (aged18-80 years; hemodynamics at baseline showing mPAP ≥25 mmHg, PAWP ≤15 mmHg, PVR >3 WU [240 dyn/s/cm-5). All patients had data available at baseline and first follow-up (3 to 12 months after treatment initiation) on 6MWD, NT-proBNP, and FC.

The prognostic value of adding assessments of 6MWD, NT-proBNP, and FC to previously used PAH endpoints and risk stratification tools was evaluated by comparing how well the previous vs enhanced endpoint predicted survival in the study cohort from baseline to follow-up. Notably, investigators found that during the study period, 189 (31.7%) patients died, 8 (1.3%) underwent lung transplant, and 34 (5.7%) were lost to follow-up. Estimated survival rates for the study cohort were 95.0% after 1 year, 76.3% after 3 years, and 65.5% after 5 years.

Although 6MWD absolute or relative improvements and absolute declines for NT-proBNP showed no predictive value, FC improvements and NT-proBNP relative declines of at least 35% were associated with improved survival. Likewise, investigators found an association between improved survival and improvements in multicomponent endpoints and risk stratification tools.

Researchers suggested that further exploration of these prognostic tools as outcome measure in PAH trials would be valuable. They concluded, “While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD and NT-proBNP were associated with improved survival.”

Study limitations included age and comorbidity bias as well as non-evaluation of widely used risk stratification tools.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author disclosures.

Reference

Hoeper MM, Pausch C, Olsson KM, et al. Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis. J Heart Lung Transplant. Published online March 22, 2022. doi:10.1016/j.healun.2022.03.011