NSTE-ACS ESC Guidelines Recommend Prasugrel as the Preferred P2Y12 Inhibitor: A Contrarian View

In the 2020 European Society of Cardiology guidelines on non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the experts proposed to put an end to the equipoise of ticagrelor and prasugrel in addition to aspirin in patients with NSTE-ACS who proceed to percutaneous coronary intervention (PCI). They gave a strong level of recommendation (IIa) in favor of prasugrel over ticagrelor in these patients. We challenge this proposition, which was mainly driven by the results of ISAR-REACT 5, an open-label prospective head-to-head study of a prasugrel-based strategy compared with a ticagrelor-based strategy in patients with ACS undergoing PCI. In addition to the methodological concerns regarding the ISAR-REACT 5 study, we also question this decision in light of the ISAR-REACT 5 diabetes mellitus subgroup analysis and previous studies and meta-analysis that showed no difference between ticagrelor and prasugrel in patients with ACS. Although we agree with the "one size does not fit all" concept for antiplatelet regimens in patients with ACS who proceed to PCI, we believe that the decision to strongly favor prasugrel was premature and not supported enough by the ISAR-REACT 5 results. In our opinion, equipoise remains between the ticagrelor- and prasugrel-based strategies and more data are needed to settle the debate.