Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study

Abstract

BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/ mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score.

Prediction of pulmonary hypertension in older adults based on vital capacity and systolic pulmonary artery pressure

“…In these patients PH diagnosis is usually difficult, because symptom progression can be subtle and early risk assessment is of paramount importance. [27][28][29] In such a population integration of parameters of LFT and echo seems reasonable. Integration of a greater number of variables into a prediction model of PH does not facilitate prediction due to the high interdependence of the factors.…”

BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing?

“…Patients achieving all three low-risk criteria (WHO/ New York Heart Association FC I or II, 6MWD >440 m, and BNP <50 ng•L −1 or NT-proBNP <300 ng•L −1 ) had 2-, 3-and 5-year survival of 100%, 99% and 97%, respectively. This method has since been validated in data from the Phase 3 GRIPHON trial, which reported a 94% reduced risk of morbidity/mortality in patients with all three low-risk criteria versus those with no low-risk values [37].…”

Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension

“…Steps to a novel composite endpoint The ability of the different risk assessment tools to discriminate not only between the different risk profiles but also between treatment arms was tested post-hoc in the PATENT-1 and -2, as well as in the GRIPHON and AMBITION studies. 30,[38][39][40] Three abbreviated versions of this risk stratification model were previously evaluated in patients with PAH in the French, Swedish and COMPERA registries. Application of the REVEAL risk score (RRS) to the PATENT study database showed similar results in terms of improvement and deterioration in favour of the verum group (riociguat), however a considerable placebo response during treatment appeared at 12 weeks.…”