BACKGROUND
Ticagrelor is an oral, reversible, direct-acting inhibitor of the
adenosine diphosphate receptor P2Y12 that was tested
against clopidogrel in the PLATO trial. Remarkably for the oral
antiplatelet agents, PLATO Investigators reported that ticagrelor
reduced death from vascular causes (4.0% vs. 5.1%, P = 0.001) and
death from any cause (4.5%, vs. 5.9%
P<0.001).1 Such a strong mortality benefit
was surprising because of opposite death counts in the Phase II DISPERSE
studies, the mismatch between reasonable myocardial infarction and very
high death rates in PLATO, the inverse US outcomes, the unusually
delayed timing of benefit, the last minute change of trial governance
from the TIMI Group to the sponsor, the late introduction of electronic
clinical research forms (eCRF),2 and some striking
“errors” revealed by the FDA, including for example, a clopidogrel
patient who was reported dead but later experienced non-fatal
bleeding.3 However, until now, no hard evidence of
misreported death records with definite proof was publicly available. As
of today, ticagrelor holds a superiority recommendation over clopidogrel
for acute coronary syndromes in European,4Canadian,5 and American 6 guidelines
based mostly on the results of the PLATO trial.1