Abstract 19111: XANTHIPPE: Examining the Effect of Ticagrelor on Platelet Activation, Platelet-Leukocyte Aggregates, and Acute Lung Injury in Pneumonia
Introduction: Despite advances in supportive treatment and antibiotic therapy for pneumonia, significant improvement in the early and late mortality have yet to be realized and increased rates of adverse cardiovascular events remain an issue. Recently, a role for platelets in inflammatory and immune responses has been identified, in addition to their established contribution to hemostasis and thrombosis. Data generated from preclinical animal models and retrospective clinical review indicates that anti-platelet therapy may improve outcomes due to lung injury and pneumonia. A retrospective analysis of the PLATO trial, in which patients with acute coronary syndrome were randomized to receive ticagrelor or clopidogrel, suggests that ticagrelor might be associated with lower mortality in subjects who subsequently developed pneumonia, which could reflect either stronger platelet P2Y12 inhibition or potential non-platelet effects of ticagrelor. The XANTHIPPE study was a prospective randomized trial undertaken to establish the effect of ticagrelor on markers of inflammation and thrombosis in patients with pneumonia and to explore its safety in this patient population.
Methods: Patients (n = 60) admitted to our institution for pneumonia were randomized within 48 hours of presentation to the hospital to receive placebo or ticagrelor (180 mg loading dose followed by 90 mg twice daily) for up to 7 days. The primary endpoint was change in platelet-leukocyte aggregates between baseline and 24 hours. Secondary endpoints included change in platelet function, biomarkers of inflammation and thrombosis, lung function, and adverse events within the first 30 days of hospitalization.
Results and Conclusions: Subjects enrolled in XANTHIPPE ranged in age from 18 – 92 of which 57% were female. A significance difference in the percent of leukocytes with attached platelets over the first 24 hours was observed between groups (-15.66 ± 6.32 vs 2.56 ± 4.18, P = 0.0212). Effects on biomarkers of platelet function, inflammation, and lung function will be presented. Our results should provide valuable mechanistic insight into platelet function in pneumonia and may demonstrate beneficial effects of anti-platelet therapy in this setting.
Author Disclosures: T.R. Sexton: None. T. Macaulay: None. L. Callahan: None. R. Charnigo: None. S.S. Smyth: None.
- © 2016 by American Heart Association, Inc.