After the successful PLATO, failed both PHILO and ATLANTIC, PEGASUS trial assessed efficacy and safety of
ticagrelor (120 mg/day and 180 mg/day) on top of
aspirin versus
aspirin alone beyond 1 year in patients with stable
coronary disease. Similar to PLATO, PEGASUS revealed reduction of composite primary endpoint after
ticagrelor at expense of extra
bleeding. However, there were major fundamental differences between the trial outcomes. Hence, the shift of evidence with
ticagrelor from PLATO to PEGASUS trials has been comprehended. In contrast to PLATO, in PEGASUS there were more premature permanent
ticagrelor discontinuations (
PPTD): RR=1.35; 95%CI 1.29-1.42, p<0.0001; significant excess of
cancer deaths (RR=1.46; 95%CI 1.02-2.06,p=0.034), trend to more
sepsis deaths (RR=1.29; 95%CI 0.76-2.20), and most importantly identical all-cause mortality (RR=1.00; 95%CI 0.86-1.16, p=0.99) versus placebo. Applied conservative TIMI
bleeding classification in PEGASUS did not correspond with
PPTD rate, with potential heavy underreporting of hemorrhagic events. Finally, unexplained late addition of 198 primary events in PEGASUS is concerning. PEGASUS failed to confirm
ticagrelor mortality benefit reported in PLATO, but rather discover additional shortcomings.