Study Summary

The multicenter ISAR-REACT 5 trial tested the efficacy and safety of prasugrel compared with ticagrelor in patients with ACS in whom invasive management was planned (n = 4,018). Patients presenting with unstable angina, NSTEMI, or STEMI and scheduled for coronary angiography were randomly assigned to receive prasugrel (loading dose: 60 mg; maintenance dose: 10 mg) or ticagrelor (loading dose: 180 mg; maintenance dose: 90 mg twice daily). Loading doses were permitted for both treatment arms prior to angiography for patients with STEMI, whereas upstream loading was delayed until after angiography among patients assigned to prasugrel. Exclusion criteria included a history of stroke, TIA, intracranial hemorrhage, intracranial neoplasm, AVM, and thrombocytopenia. Patients were treated with PCI in 83.4% of the ticagrelor arm and 84.8% of the prasugrel arm. At 1 year, the primary composite endpoint of death, MI, or stroke occurred more frequently in the ticagrelor than the prasugrel arm (9.3% versus 6.9%, P = 0.006). There was no significant difference between the two groups in the incidence of BARC types 3–5 bleeding or stroke.

Commentary

Study Strengths: This was a large, multicenter, multinational study. Uniquely, the trial compared performance of different antiplatelet strategies as opposed to simply comparing two different antiplatelet drugs.

Study Limitations: Adjudication of outcomes was blinded, however, administration of the study drugs was open-label, which may impact adherence and perceived tolerance to medication. Indeed, a higher proportion of patients stopped taking the assigned therapy in the ticagrelor group than in the prasugrel group (15% versus 12%). The majority of patients underwent PCI, limiting the generalizability of the findings to patients not treated with PCI.

Next Steps/Clinical Perspective: The results of this study were surprising, as ticagrelor was expected to be the superior drug. The rate of ischemic events in the prasugrel group was lower than in earlier randomized studies. Although thrombotic risk was reduced, no differences in bleeding rates were shown, a somewhat counterintuitive result.

Trial Reference

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Schüpke  S, Neumann  F-J, Menichelli  M, et al. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N. Engl. J. Med. doi: 10.1056/NEJMoa1908973.