Excessive Long-Term Platelet Inhibition With Prasugrel or Ticagrelor and Risk of Infection

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

“…The potential link between infections and antiplatelet therapy still represents a hypothesis to be explored rather than anything definite that can be concluded. However, long-term platelet inhibition may cause excess of infections and sepsis since exhausted platelets will not form strong aggregates with neutrophils and macrophages(16).Overshooting Target Events: Per PEGASUS protocol, recruitment began inOctober 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial was planned to continue until the latest of either 1,360 adjudicated primary end points are accrued, or the last patient randomized has been followed for at least 12 months(9,10), and, therefore, should be stopped no later than April 2014.…”

Infections Deaths in the PLATO Trial

“…The relations between infections, hemostasis, and potency of antithrombotic therapy are intertwined but important, especially after utilization of current aggressive dual antiplatelet strategies following coronary revascularization. 1 Indeed, such complex interventions per se often require use of numerous devices into and out of the arterial circulation, and these procedures may cause bacteremia 2 or even septicemia. 3 Since already established shortcomings following clopidogrel may include impaired wound healing and increased postsurgery infections, 4,5 more powerful antiplatelet strategies could present even greater risks.…”