Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension.
Circulation
; 139(21): 2440-2450, 2019 05 21.
Article
em En
| MEDLINE
| ID: mdl-30982349
ABSTRACT
BACKGROUND:
NT-proBNP (N-terminal pro brain natriuretic peptide) levels are included in the multiparametric risk assessment approach for pulmonary arterial hypertension (PAH) outlined in PAH guidelines. However, data supporting the use of NT-proBNP risk thresholds in assessing prognosis in PAH are limited. The GRIPHON trial (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) provides an opportunity to assess the prognostic value of NT-proBNP thresholds in a controlled clinical trial and to evaluate the response to selexipag according to these thresholds.METHODS:
The event-driven GRIPHON trial randomly assigned patients to selexipag or placebo. NT-proBNP was measured at regular intervals in GRIPHON. Here, patients were categorized post hoc into low, medium, and high NT-proBNP subgroups according to 2 independent sets of thresholds (1) baseline tertiles <271 ng/L; 271 to 1165 ng/L; >1165 ng/L; and (2) 2015 European Society of Cardiology/European Respiratory Society guidelines cutoffs <300 ng/L; 300 to 1400 ng/L; >1400 ng/L. Hazard ratios (selexipag versus placebo) with 95% CIs were calculated for the primary end point (composite morbidity/mortality events) by NT-proBNP category at baseline using Cox proportional-hazards models, and at any time during the exposure period using a time-dependent Cox model.RESULTS:
With both thresholds, baseline and follow-up NT-proBNP categories were highly prognostic for future morbidity/mortality events during the study ( P<0.0001). In the time-dependent analysis, the risk of experiencing a morbidity/mortality event was 92% and 83% lower in selexipag-treated patients with a low and medium NT-proBNP level, and 90% and 56% lower in placebo-treated patients with a low and medium NT-proBNP level, in comparison with patients with a high NT-proBNP level. Selexipag reduced the risk of morbidity/mortality events across all 3 NT-proBNP categories in both the baseline and time-dependent analyses, with a more pronounced treatment benefit of selexipag seen in the medium and low NT-proBNP subgroups (interaction P values 0.20 and 0.007 in the baseline and time-dependent analyses).CONCLUSIONS:
These analyses further establish the prognostic relevance of NT-proBNP levels in PAH and provide first evidence for the association of NT-proBNP level and treatment response. Using 2 similar sets of thresholds, these analyses support the relevance of the low, medium, and high NT-proBNP categories as part of the multiparametric risk assessment approach outlined in the European Society of Cardiology/European Respiratory Society guidelines for the management of PAH patients. CLINICAL TRIAL REGISTRATION URL https//www.clinicaltrials.gov . Unique identifier NCT01106014.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Artéria Pulmonar
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Peptídeo Natriurético Encefálico
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Pressão Arterial
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Hipertensão Arterial Pulmonar
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article