Exploring the reduction in myocardial infarctions in the PLATO trial: Which patients benefited on ticagrelor vs. clopidogrel?

AbstractContext Ticagrelor showed significant reductions in myocardial infarctions (MIs) compared to clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. However, there was no explanation as to whether there was an equal distribution of benefit throughout acute coronary syndrome (ACS) types. Objective To ascertain the safety and efficacy of ticagrelor compared to clopidogrel based on the type of ACS index event (ST-segment elevation myocardial infarction [STEMI], non-ST-segment elevation myocardial infarction [NSTEMI] and unstable angina [UA]). Results The FDA Complete Response Review (CRR) indicates that when MIs were broken down by index event type, ticagrelor fared better than clopidogrel only in patients with STEMI (136/3496 [4.2%] vs. 184/3530 [5.7%], hazard ratio (HR) 0.74 [0.59-0.93]), whereas patients with NSTEMI and UA showed no significant difference (288/4005 [7.9%] vs. 324/950 [8.9%], HR 0.87 [0.74-1.02] and 76/1549 [5.2%] vs. 75/1563 [5.1%], HR 1.02 [0.75-1.42]). Moreover, STEMI patients receiving early (<24 h) percutaneous coronary intervention (PCI) showed an increase in 30 day MI or cardiovascular (CV) death on ticagrelor compared to clopidogrel, in both the United States (US) and outside-US (OUS) regions (5.0% vs. 1.8% and 3.2% vs. 2.9%, respectively). Conclusions Ticagrelor significantly reduced MIs compared to clopidogrel only in STEMI patients, with those receiving early PCI having worse outcomes with ticagrelor. Despite, NSTEMI patients showing no significant reduction in MI with ticagrelor vs. clopidogrel, CV mortality was significantly reduced. In summary, we cannot be sure what is driving the STEMI-MI benefit, the NSTEMI-CV mortality benefit, nor the overall mortality benefit for ticagrelor-treated patients compared to clopidogrel treated patients.