Mark R Thomas1,2, Stefan K James3,4, Richard C Becker5, Anders Himmelmann6, Hugo A Katus7, Christopher P Cannon8, Philippe Gabriel Steg9,10,11,12, Agneta Siegbahn4,13, Tatevik Lakic4, Robert F Storey1, Lars Wallentin3,4. 1. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK. 2. Institute of Cardiovascular Sciences and UHB and SWBH NHS Trusts, University of Birmingham, UK. 3. Department of Medical Sciences, Cardiology, Uppsala University, Sweden. 4. Uppsala Clinical Research Center, Uppsala University, Sweden. 5. University of Cincinnati College of Medicine, USA. 6. AstraZeneca Research and Development, Gothenburg, Sweden. 7. Medizinishe Klinik, Universitätsklinikum Heidelberg, Germany. 8. TIMI Study Group, Brigham and Women's Hospital, USA. 9. INSERMU1148, Paris, France. 10. Département Hospitalo-Universitaire FIRE, Hôpital Bichat, France. 11. Université Paris-Diderot, Sorbonne-Paris Cité, France. 12. NHLI Imperial College, Royal Brompton Hospital, UK. 13. Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden.
Abstract
BACKGROUND: Inflammation plays a major role in the pathophysiology of coronary artery disease. We aimed to determine whether baseline inflammatory markers were associated with clinical outcomes and the observed superiority of ticagrelor compared to clopidogrel in patients with acute coronary syndromes in the PLATO study. METHODS: Blood samples were collected from 16,400 patients within 24 hours of the onset of acute coronary syndrome, at the time of random assignment to ticagrelor or clopidogrel in the PLATO study and prior to invasive procedures. The differential white blood cell count and plasma levels of C-reactive protein, interleukin-6 and interleukin-10 were determined and their relationships with clinical outcomes were assessed according to quartiles and using continuous models. The substudy primary endpoint was a composite of cardiovascular death and myocardial infarction. RESULTS: Compared to the lowest quartile, the risk of the primary endpoint was significantly elevated in patients in the highest quartile of white blood cell count (hazard ratio (HR) 1.30; P=0.01), neutrophil count (HR 1.33; P=0.007), monocyte count (HR 1.24; P=0.004), C-reactive protein (HR 1.93; P<0.001) and interleukin-6 (HR 2.29; P<0.001). This was predominantly driven by an association with cardiovascular death. Following adjustment for clinical characteristics, troponin, cystatin C and N-terminal pro-brain-type natriuretic peptide, only white blood cell count and neutrophil count maintained a significant association with the primary endpoint. Ticagrelor had a consistent relative cardiovascular benefit compared to clopidogrel in each quartile of each of the inflammatory markers. CONCLUSIONS: Acute coronary syndrome patients with elevated levels of baseline inflammatory markers are at increased risk of adverse cardiovascular events, particularly cardiovascular death. The consistent cardiovascular benefit of ticagrelor compared to clopidogrel tended to confer a greater absolute risk reduction in patients with the highest levels of inflammatory markers, as they were at highest risk.
BACKGROUND: Inflammation plays a major role in the pathophysiology of coronary artery disease. We aimed to determine whether baseline inflammatory markers were associated with clinical outcomes and the observed superiority of ticagrelor compared to clopidogrel in patients with acute coronary syndromes in the PLATO study. METHODS: Blood samples were collected from 16,400 patients within 24 hours of the onset of acute coronary syndrome, at the time of random assignment to ticagrelor or clopidogrel in the PLATO study and prior to invasive procedures. The differential white blood cell count and plasma levels of C-reactive protein, interleukin-6 and interleukin-10 were determined and their relationships with clinical outcomes were assessed according to quartiles and using continuous models. The substudy primary endpoint was a composite of cardiovascular death and myocardial infarction. RESULTS: Compared to the lowest quartile, the risk of the primary endpoint was significantly elevated in patients in the highest quartile of white blood cell count (hazard ratio (HR) 1.30; P=0.01), neutrophil count (HR 1.33; P=0.007), monocyte count (HR 1.24; P=0.004), C-reactive protein (HR 1.93; P<0.001) and interleukin-6 (HR 2.29; P<0.001). This was predominantly driven by an association with cardiovascular death. Following adjustment for clinical characteristics, troponin, cystatin C and N-terminal pro-brain-type natriuretic peptide, only white blood cell count and neutrophil count maintained a significant association with the primary endpoint. Ticagrelor had a consistent relative cardiovascular benefit compared to clopidogrel in each quartile of each of the inflammatory markers. CONCLUSIONS: Acute coronary syndrome patients with elevated levels of baseline inflammatory markers are at increased risk of adverse cardiovascular events, particularly cardiovascular death. The consistent cardiovascular benefit of ticagrelor compared to clopidogrel tended to confer a greater absolute risk reduction in patients with the highest levels of inflammatory markers, as they were at highest risk.
Authors: Ana C A Casarotti; Daniela Teixeira; Ieda M Longo-Maugeri; Mayari E Ishimura; Maria E R Coste; Henrique T Bianco; Flavio T Moreira; Amanda F Bacchin; Maria C Izar; Iran Gonçalves; Adriano Caixeta; Gilberto Szarf; Ibraim M Pinto; Francisco A Fonseca Journal: Biosci Rep Date: 2021-02-26 Impact factor: 3.840
Authors: Gorav Batra; Henrik Renlund; Vijay Kunadian; Stefan K James; Robert F Storey; P Gabriel Steg; Hugo A Katus; Robert A Harrington; C Michael Gibson; Andrzej Budaj; Agneta Siegbahn; Lars Wallentin Journal: Eur Heart J Acute Cardiovasc Care Date: 2022-06-07