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Ticagrelor and the prevention of cardiovascular mortality: more than just platelet inhibition?
  1. Michael A Gaglia Jr
  1. Correspondence to Dr Michael A Gaglia Jr, Division of Cardiovascular Medicine, University of Southern California Keck School of Medicine, 1510 San Pablo St., HCC I, Suite 322, Los Angeles, CA 91030, USA; mgaglia{at}usc.edu

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In their recent article, Varenhorst and colleagues present an analysis from the Platelet Inhibition and Patient Outcomes (PLATO) trial comparing the causes of death in acute coronary syndrome (ACS) patients on ticagrelor versus clopidogrel. Among the 905 patients who died postenrollment, the investigators showed that, overall, vascular death (3.8% vs 4.8%, p=0.001) was significantly less frequent with ticagrelor in comparison with clopidogrel. This appeared to be driven by a difference in sudden death (0.7% vs 1.1%, p=0.006), without a difference in mortality from acute myocardial infarction (MI), heart failure, arrhythmia, or bleeding events. Additionally, although there was no difference in non-vascular deaths directly caused by infection, there were fewer deaths with infection as a primary or contributing cause with ticagrelor versus clopidogrel (0.5% vs 0.8%, p=0.03).1

The PLATO trial showed an overall reduction in all-cause and cardiovascular mortality with ticagrelor versus clopidogrel, in addition to a decrease in MI and stent thrombosis.2 It is tempting to conclude that this mortality benefit is a function of more effective P2Y12 receptor inhibition. Indeed, pharmacodynamic studies have shown that ticagrelor results in more rapid, potent and consistent levels of platelet inhibition than clopidogrel, in patients with stable coronary artery disease and ACS. In the present study, however, there was no significant difference between ticagrelor and clopidogrel in regards to death from MI (1.9% vs 2.1%, p=0.43). If the mortality benefit were largely due to more effective platelet inhibition, one might expect a more marked difference in death from MI. It is conceivable that some of the cases of sudden death were potentially due to stent thrombosis, which might be prevented with ticagrelor. These cases would qualify as ‘possible’ stent thrombosis, but there is evidence from the PLATO trial that ticagrelor decreases definite, probable …

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