Clopidogrel is safer than ticagrelor in regard to bleeds: a closer look at the PLATO trial

Objective: To compare hemorrhagic events between clopidogrel and ticagrelor in the Platelet Inhibition and Patient Outcomes (PLATO) trial.

Methods: We examined the FDA Medical Review.

Results: Compared to clopidogrel, ticagrelor significantly increased spontaneous bleeds, major bleeds, major plus minor bleeds, and major plus minor plus minimal bleeds. Ticagrelor also increased both major and fatal/life-threatening bleeds versus clopidogrel when CABG was performed between 24 and 96 h after stopping medication, which was also accompanied by a larger volume of chest tube drainage and transfusions. Moreover, ticagrelor increased CABG-related bleeding versus clopidogrel in those patients who did not wait until day 5 after stopping treatment to have CABG. Additionally, compared to clopidogrel, ticagrelor increased the risk of hematuria (RR=1.91; 95% CI: 0.95-3.83), intracranial hemorrhage or subdural or other hematoma (RR 1.87; 95% CI: 1.02-3.42), subcutaneous hemorrhage, ecchymosis, hematoma (RR=1.63; 95% CI: 0.84-3.17), epistaxis (RR=1.49; 95% CI: 0.67-3.32), retroperitoneal hematoma or hemorrhage (RR=1.49; 95% CI: 0.53-4.19), gastrointestinal/anal bleed (RR=1.23; 95% CI: 0.93-1.64) and bleed/hematoma (RR=1.21, 95% CI: 1.02-1.43).

Conclusions: Clopidogrel is safer than ticagrelor in regard to bleeding. Additionally, ticagrelor's purported faster antiplatelet 'offset' is substantially longer than its pharmacokinetics indicate. Considering the fact that the mortality, stent thrombosis and myocardial infarction 'benefit' of ticagrelor have recently been challenged, and that the increase in stroke on ticagrelor has recently been shown to be worse than originally published, the decision to use ticagrelor over clopidogrel in the face of a higher risk for bleeds is not advised.