Key result
Elevated baseline inflammatory markers were associated with increased cardiovascular risk (P<0.001), and ticagrelor maintained a consistent relative benefit over clopidogrel across all quartiles.
Why the study?
Because inflammation plays a major role in CAD, the authors sought to determine whether baseline inflammatory markers are associated with clinical outcomes and the superiority of ticagrelor over clopidogrel in ACS.
Do baseline inflammatory markers predict outcomes and modify the treatment effect of ticagrelor versus clopidogrel in patients with acute coronary syndromes?
RCT (n=16,400)
random assignment
Do baseline inflammatory markers predict outcomes and modify the treatment effect of ticagrelor versus clopidogrel in patients with acute coronary syndromes?
p-value: p=<0.001
Elevated baseline inflammatory markers, particularly white blood cell and neutrophil counts, independently predict adverse outcomes in ACS but do not attenuate the relative cardiovascular benefit of ticagrelor over clopidogrel.
Elevated baseline markers identify higher-risk ACS patients; supports consistent ticagrelor benefit independent of inflammation.
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: <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.
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Thomas et al. (2019) conducted an RCT in Acute coronary syndromes (n=16,400). Ticagrelor vs. Clopidogrel was evaluated on Composite of cardiovascular death and myocardial infarction (p=<0.001). Elevated baseline inflammatory markers were associated with increased cardiovascular risk (P<0.001), and ticagrelor maintained a consistent relative benefit over clopidogrel across all quartiles.
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