BACKGROUND: Historically, clinical trials in patients (pts) w/pulmonary arterial hypertension (PAH) evaluate six-minute walk distance (6MWD) as the primary endpoint to assess exercise capacity. Common secondary endpoints include functional class (FC) and brain natriuretic peptide (BNP) to assess PAH disease severity and right heart function, respectively. Recent PAH studies have employed morbidity and mortality as a primary endpoint, and while pertinent, require large and lengthy clinical trials and often cannot be used in clinical practice to monitor treatment response.
OBJECTIVE: To examine the relationship between 3 established noninvasive endpoints and long-term health outcomes in PAH clinical trials and registries.
METHODS: A literature review was performed using search terminology focused on PAH non-invasive endpoints and related outcomes. PubMed, MEDLINE, Embase and Cochrane were searched from Jan 1997-Apr 2018. Conference abstracts (2016-2017) were searched from American Thoracic Society, American College of Chest Physicians and International Society for Pharmacoeconomics and Outcomes Research. Studies were selected in accordance with predefined inclusion/ exclusion criteria based on disease population, interventions, outcomes and study design. The article selection process included two levels: (1) titles and abstracts were identified and reviewed (2) full-texts of articles selected at level 1 were obtained and reviewed for relevance.
RESULTS: A total of 771 unique records were retrieved for review from the database search for level 1 screening. Among these, 60 studies and 9 reviews were selected for level 2 screening. Upon review of the fulltext articles, a total of 25 studies were deemed eligible for inclusion in the report. Literature findings strongly supported the importance of measuring PAH non-invasive endpoints in both clinical trials and clinical practice. Baseline and change in 6MWD was associated with event-free survival including death, heart/lung transplantation, atrial septostomy, hospital admission due to PAH and disease worsening. FC and BNP can help identify PAH patients at high risk for multiple outcomes such as treatment modification, transplantation and hospitalization. European PAH registry studies show that 6MWD, FC and BNP are the strongest predictor of outcome and when used in combination can better determine disease prognosis.
CONCLUSIONS: Given their association with long-term health outcomes and practicality for assessment, 6MWD, FC and BNP should continue to be assessed in clinics and clinical research.
