title: Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study.
abstract: In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.
authors.affiliation: Department of Cardiovascular Science, University of Sheffield , Sheffield , UK .
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Christoph
authors.initials: C
authors.lastname: Varenhorst
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: Joseph
authors.initials: J
authors.lastname: Ycas
authors.forename: Steen E
authors.initials: SE
authors.lastname: Husted
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Nils
authors.initials: N
authors.lastname: Åsenblad
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced* / Q000401:mortality; D018805:Sepsis / Q000139:chemically induced* / Q000401:mortality; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Clopidogrel; coronary artery disease; platelet aggregation inhibitors; pneumonia; sepsis; ticagrelor