Article ; Online: Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension.
2019 Volume 139, Issue 21, Page(s) 2440–2450
Abstract: Background: NT-proBNP (N-terminal pro brain natriuretic peptide) levels are included ...
| 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 [PGI 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. |
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| MeSH term(s) | Acetamides/therapeutic use ; Adolescent ; Adult ; Aged ; Antihypertensive Agents/therapeutic use ; Arterial Pressure/drug effects ; Biomarkers/blood ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Pulmonary Arterial Hypertension/blood ; Pulmonary Arterial Hypertension/drug therapy ; Pulmonary Arterial Hypertension/mortality ; Pulmonary Arterial Hypertension/physiopathology ; Pulmonary Artery/drug effects ; Pulmonary Artery/physiopathology ; Pyrazines/therapeutic use ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult |
| Chemical Substances | Acetamides ; Antihypertensive Agents ; Biomarkers ; Peptide Fragments ; Pyrazines ; pro-brain natriuretic peptide (1-76) ; Natriuretic Peptide, Brain (114471-18-0) ; selexipag (5EXC0E384L) |
| Language | English |
| Publishing date | 2019-04-13 |
| Publishing country | United States |
| Document type | Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 80099-5 |
| ISSN | 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499 |
| ISSN (online) | 1524-4539 |
| ISSN | 0009-7322 ; 0069-4193 ; 0065-8499 |
| DOI | 10.1161/CIRCULATIONAHA.118.039360 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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