Ticagrelor shift from PLATO to PEGASUS: Vanished mortality benefit, excess cancer deaths, massive discontinuations, and overshooting target events

International Journal of Cardiology
Victor L Serebruany

Abstract

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 additio...Continue Reading

References

Jan 16, 2007·The American Journal of Cardiology·Victor L Serebruany, Dan Atar
Sep 1, 2009·The New England Journal of Medicine·Lars WallentinMona Thorsén
Oct 24, 2013·Expert Review of Cardiovascular Therapy·Sameer BansilalMarc S Sabatine
Dec 11, 2014·The New England Journal of Medicine·Gilles Montalescot, Arnoud W van 't Hof
Mar 17, 2015·The New England Journal of Medicine·Marc P BonacaUNKNOWN PEGASUS-TIMI 54 Steering Committee and Investigators
May 8, 2015·Thrombosis and Haemostasis·Victor SerebruanyAlexander Dukhanin
Sep 24, 2015·The New England Journal of Medicine·Marc P BonacaMarc S Sabatine

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Citations

Oct 30, 2015·Expert Review of Cardiovascular Therapy·Victor L SerebruanyMoo Hyun Kim
Apr 30, 2016·International Journal of Cardiology·Victor Serebruany, Ales Tomek
Jul 29, 2017·Cancer Metastasis Reviews·Marek Z WojtukiewiczKenneth V Honn
Oct 19, 2017·European Heart Journal. Cardiovascular Pharmacotherapy·Jacek KubicaEliano P Navarese
Feb 26, 2020·International Journal of Molecular Sciences·Alexandre MansourIsabelle Gouin-Thibault
Oct 29, 2020·American Journal of Therapeutics·Victor SerebruanyUNKNOWN Clinical Trials Outcomes Verification Task Force
Jul 30, 2021·Frontiers in Oncology·Attila BraunElmina Mammadova-Bach

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