Schüpke S, Neumann FJ, Menichelli M, et al.; ISAR-REACT 5 Trial Investigators. Ticagrelor or
Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 Oct 17;381(16):1524-1534. doi: 10.1056/NEJMoa1908973.
Pablo Avanzas, Hospital Universitario Central Asturias
Summary of the trial
In this multicenter, randomized, open-label trial, the authors randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding.
A total of 4018 patients underwent randomization. A primary-end point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P=0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P=0.46).
Randomized trials have shown the superiority of prasugrel and ticagrelor over clopidogrel in patients with acute coronary syndromes, and both drugs received a class I recommendation for use in patients who have acute coronary syndromes with or without ST-segment elevation. However, data are lacking on the relative merits of treatment for 1 year with ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned.
In this investigator-initiated, randomized, multicenter trial, prasugrel was superior to ticagrelor with respect to the composite end point of death, myocardial infarction, or stroke at 1 year after randomization in patients with acute coronary syndromes who were scheduled to undergo invasive evaluation. This was an unexpected finding. This result was driven by a significant reduction of 1.8 percent-age points in the incidence of recurrent (spontaneous and percutaneous coronary intervention [PCI]–associated) myocardial infarction, with no significant between-group difference in the incidence of major bleeding. The results were consistent across the whole spectrum of presentation of acute coronary syndromes.
Limitations of this trial should be also acknowledged:
- Lack of a double-dummy design,
- Events were predominantly ascertained through telephone contact with the patients
- Approximately 19% of the patients were not receiving a trial drug at discharge
Overall, although long-term data and additional comparative-effectiveness data are lacking, and in the light of these results, prasugrel has now become the P2Y12 receptor inhibitor of choice in patients with acute coronary syndromes. It should be used instead of ticagrelor in appropriately selected patients with this condition.