P2Y12 inhibition in acute coronary syndromes treated with percutaneous intervention - Understanding the debate on Prasugrel or Ticagrelor

After more than 10 years of routine clinical use, a debate about the preference of prasugrel over ticagrelor has been unveiled following publication of the ISAR-REACT 5 trial, an investigator-initiated trial directly comparing both substances as part of dual anti-platelet therapy following interventional treatment in patients with acute coronary syndromes (ACS). Both substances had been tested in trials, approved by authorities and subsequently recommended by guidelines according to the strategy applied in the respective approval trial. This resulted in prasugrel tested in TRITON only be given after diagnostic coronary angiography in the absence of ST-segment elevations (NSTE-ACS) and ticagrelor tested in PLATO being administered even before diagnostic coronary angiography in all forms of acute coronary syndromes. Whichever way was safest and most efficient, had never been clarified before. ISAR-REACT 5 showed superior efficacy of prasugrel over ticagrelor in general, and of deferred administration of prasugrel over pre-treatment with ticagrelor in NSTE-ACS patients undergoing percutaneous coronary interventions. Subsequently, in 2020 the European guidelines for NSTE-ACS adopted both positions in recommending the respective preference. Afterwards, a confrontational debate erupted between those favouring the ISAR-REACT 5 results and their implementation in guidelines and others still preferring the generalized interpretation of the overall study results from PLATO. In this review, we reflect the history leading to trial design of TRITON and PLATO and theway this subsequently impacted on clinical practice and guideline recommendations. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

A debate about the preference of prasugrel over ticagrelor has been sparked by the publication of the ISAR-REACT 5 trial, which compared both substances in patients with ACS. The trial showed superior efficacy of prasugrel over ticagrelor in general, and of deferred administration of prasugrel over pre-treatment with ticagrelor in NSTE-ACS patients undergoing percutaneous coronary interventions. The European guidelines for NSTE-ACS have adopted these preferences.