1. Growth differentiation factor-15 is not modified by sacubitril/valsartan and is an independent marker of risk in patients with heart failure and reduced ejection fraction: the PARADIGM-HF trial.
- Author
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Bouabdallaoui, Nadia, Claggett, Brian, Zile, Michael R., McMurray, John J.V., O'Meara, Eileen, Packer, Milton, Prescott, Margarett F., Swedberg, Karl, Solomon, Scott D., Rouleau, Jean L., and PARADIGM-HF Investigators and Committees
- Subjects
AMINOBUTYRIC acid ,HETEROCYCLIC compounds ,ANGIOTENSIN receptors ,CLINICAL trials ,COMPARATIVE studies ,CYTOKINES ,ENZYME-linked immunosorbent assay ,HEART failure ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESEARCH funding ,TIME ,EVALUATION research ,TREATMENT effectiveness ,DISEASE progression ,STROKE volume (Cardiac output) ,THERAPEUTICS - Abstract
Aims: Growth differentiation factor-15 (GDF-15) is associated with adverse prognosis in cardiovascular (CV) and non-CV diseases. We evaluated the association of GDF-15 with CV and non-CV outcomes in the PARADIGM-HF trial.Methods and Results: In 1935 patients with heart failure and reduced ejection fraction (HFrEF) in PARADIGM-HF, median GDF-15 values were elevated and similar in sacubitril/valsartan and enalapril patients (1626 ng/L and 1690 ng/L, respectively). Diabetes, age, creatinine, high-sensitive troponin T, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class III/IV were most strongly associated with elevated GDF-15 values (all P < 0.001) (adjusted R2 = 0.3857). Baseline GDF-15 and changes in GDF-15 at both 1 month and 8 months (log-transformed) were associated with subsequent mortality and CV events. Each 20% increment in baseline GDF-15 value was associated with a higher risk of mortality [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.08-1.18, P < 0.001], the combined endpoint of CV death or hospitalization for heart failure (adjusted HR 1.09, 95% CI 1.05-1.14, P < 0.001) and heart failure death (adjusted HR 1.16, 95% CI 1.05-1.28, P < 0.001). Changes in GDF-15 were not influenced by assigned therapy (all P-values ≥ 0.1).Conclusion: In patients with ambulatory HFrEF, GDF-15 is not modified by sacubitril/valsartan and is strongly associated with mortality and CV outcomes, suggesting that GDF-15 is a marker of poor outcomes in these patients.Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01035255. [ABSTRACT FROM AUTHOR]- Published
- 2018
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