Daniel Lindholm1,2, Stefan K James3,2, Maria Bertilsson2, Richard C Becker4, Christopher P Cannon5, Evangelos Giannitsis6, Robert A Harrington7, Anders Himmelmann8, Frederic Kontny9, Agneta Siegbahn2,10, Philippe Gabriel Steg11,12,13,14, Robert F Storey15, Matthijs A Velders3,2, W Douglas Weaver16, Lars Wallentin3,2. 1. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; daniel.lindholm@ucr.uu.se. 2. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 3. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. 4. Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, Cincinnati, OH. 5. Cardiovascular Division, Brigham and Women's Hospital and Harvard Clinical Research Institute, Boston, MA. 6. Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Germany. 7. Department of Medicine, Stanford University, Stanford, CA. 8. AstraZeneca Research and Development, Mölndal, Sweden. 9. Department of Cardiology, Stavanger University Hospital, Stavanger, Norway. 10. Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden. 11. INSERM-Unité 1148, Paris, France. 12. Assistance Publique-Hôpitaux de Paris; Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France. 13. Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France. 14. NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK. 15. Department of Cardiovascular Science, University of Sheffield, Sheffield, UK. 16. Henry Ford Heart and Vascular Institute, Detroit, MI.
Abstract
BACKGROUND: Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS. METHODS: In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI). RESULTS: For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs. CONCLUSIONS: In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from more intense and/or prolonged antithrombotic treatment. ClinicalTrials.gov Identifier: NCT00391872.
RCT Entities:
BACKGROUND: Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS. METHODS: In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI). RESULTS: For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs. CONCLUSIONS: In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from more intense and/or prolonged antithrombotic treatment. ClinicalTrials.gov Identifier: NCT00391872.
Authors: Daniel Lindholm; Stefan K James; Katja Gabrysch; Robert F Storey; Anders Himmelmann; Christopher P Cannon; Kenneth W Mahaffey; Philippe Gabriel Steg; Claes Held; Agneta Siegbahn; Lars Wallentin Journal: JAMA Cardiol Date: 2018-12-01 Impact factor: 14.676
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