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.