Stefanie Schüpke (Deutsches Herzzentrum München, and Technische Universität München, Munich, Germany) told ESC delegates today that using prasugrel rather than ticagrelor to treat patients with acute coronary syndromes is associated with a significant reduction in the incidence of death, myocardial infarction or stroke. This finding went against her original hypothesis that ticagrelor would prove superior to prasugrel.
Schüpke explained that both drugs are recommended, for one year, for the management of acute coronary syndromes with a Class I indication but observed: “The relative merits of a ticagrelor-based vs. a prasugrel-based strategy in acute coronary syndrome patients with and without ST-segment elevation at one year are not known.” Therefore, the aim of the investigator-initiated ISAR-REACT 5 trial was to provide a randomised comparison of the two treatments.
According to Schüpke, at the start of the study, the assumption was that ticagrelor would be “superior to prasugrel in acute coronary syndromes patients with planned invasive strategy in terms of clinical outcomes.” This was because, unlike prasugrel, ticagrelor can be used to pretreat all patients with acute coronary syndromes. Writing in their paper (published simultaneously with the ESC presentation) in the New England Journal of Medicine, Schüpke and colleagues explain: “On the basis of the rationale that a stronger platelet inhibition at the time of percutaneous coronary intervention (PCI) reduces periprocedural thrombotic risk, the pretreatment strategy with ticagrelor was considered to be advantageous.” A previous study showed that pretreatment with prasugrel in patients with non ST-segment elevation (NSTE) acute coronary syndromes does not provide any benefit but is associated with a significant increase in bleeding. Therefore, in patients with NSTE acute coronary syndromes, prasugrel is administered after angiography.
In the study, 4,018 patients who presented with acute coronary syndromes for whom invasive evaluation is planned were randomised to a prasugrel-based strategy (2006) or to a ticagrelor-based strategy (2012). In the prasugrel-based strategy, patients were given a loading dose of 60mg and continued on a maintenance dose of 10mg day (or 5mg daily if older than 75 years and/or had body weight of less than 60kg). In patients without STE, the loading dose of prasugrel was administered after the result of the coronary angiography was known. In STE myocardial infarction (STEMI) patients, the drug was administered as soon as possible after randomisation. In the ticagrelor-based strategy, patients with given a loading dose of 180mg and then maintained on a dose of 90mg twice daily. In this group, all patients (with or without STE) were given the drug as soon as possible after randomisation.
The primary endpoint—a composite rate of death, myocardial infarction, or stroke at one year—was significantly lower in the prasugrel-based strategy group: 6.9% vs. 9.3% for the ticagrelor-based strategy group (Kaplan-Meier estimates; p=0.006). This finding was primarily driven by a lower rate of myocardial infarctions with prasugrel: 3% vs. 4.8% for ticagrelor. In terms of the other components of the primary endpoint, respectively, they were 3.7% vs. 4.5% for death and 1.0% vs. 1.1% for stroke. These results were consistent across all subgroups of clinical presentation (i.e., unstable angina, NSTEMI and STEMI) and the reduction in the primary endpoint with prasugrel was without an increase in major bleeding (4.8% for prasugrel vs. 5.4% for ticagrelor; p=0.46).
Speaking at a press conference prior to the ESC presentation, Schüpke said: “The results of the trial support a prasugrel-based strategy—without routine pretreatment in NSTE-acute coronary syndrome—as the first-line antiplatelet therapy for acute coronary syndrome patients.
Gilles Montalescot (Sorbonne University, ACTION Study Group, Institut de Cardiologie (AP-HP), Centre Hospitalier Universitaire Pitié-Salpêtriėre, Paris, France), who provided the discussant review for ISAR-REACT 5, echoed these comments by calling it a “landmark study” that would “impact our clinical practice and the next set of guidelines that come out next year”.