Physicians' Academy for Cardiovascular Education

Comparison of two P2Y12 inhibitors in ACS patients with diabetes

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus

Literature - Ndrepepa G, Kastrati A, Menichelli M, et al. - JACC Cardiovasc Interv 2020, 13:2238-2247.doi: 10.1016/j.jcin.2020.07.032

Introduction and methods

Patients with diabetes (DM) who present themselves with acute coronary syndrome (ACS) and in whom invasive therapy is planned, have increased platelet reactivity, reduced response to antiplatelet drugs resulting in higher risk for subsequent thrombotic events and higher mortality risk when compared to patients without diabetes [1-5]. Even after increasing clopidogrel maintenance dose in patients with DM in the OPTIMUS trial, 60% of patients did not respond optimal [6], indicating the need for better strategies of platelet inhibition in patients with DM.

The TRITON-TIMI trial and PLATO trial demonstrated superiority of either prasugrel or ticagrelor respectively over clopidogrel in DM patients. But head-to-head comparisons of ticagrelor vs. prasugrel in DM patients are lacking and the trials enrolled different patient populations. Therefore, it is not known which antiplatelet drug is preferred in DM patients presenting with ACS and planned invasive therapy.

The ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Actions for Coronary Treatment) 5 trial demonstrated superiority of prasugrel over ticagrelor in reduction the composite endpoint of death, MI, or stroke, without increasing risk of major bleeding in ACS patients undergoing PCI [7]. A prespecified analysis according to DM status was planned.

In the ISAR-REACT 5 trial, patients hospitalized for ACS with planned invasive treatment were enrolled and randomized to ticagrelor (a loading dose of 180 mg as soon as possible after randomization and continued at a maintenance dose of 90 mg twice daily) or to prasugrel (a loading dose of 60 mg after coronary angiography and continued at maintenance dose of 10 mg once daily). Information on DM was available in 4016 patients: 892 had DM and 3124 had no DM. Efficacy endpoint was a composite of death, MI, or stroke at 12 months. Safety endpoint was incidence of bleeding types 3 to 5 defined by BARC at 12 months.

Main results


In this prespecified analysis of ISAR-REACT 5 trial, there was no difference between ticagrelor and prasugrel with regard to efficacy in ACS patients with DM. In addition, safety of ticagrelor was comparable with that of prasugrel in DM patients.


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Find this article online at JACC Cardiovasc Interv 2020

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