Literature

Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published October 16, 2019

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How did ticagrelor compare to prasugrel regarding the risk of ischemic events in the trial by Schüpke et al.?

Schüpke et al. conducted a multicenter, randomized, open-label trial, which randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. Read the Original Article here.

Clinical Pearls

Q: What background issues prompted the trial by Schüpke et al.?

A: 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.

Q: Did the two study groups in the trial by Schüpke et al. differ only in terms of the study drug received?

A: A particular feature of this trial is that it did not simply compare two antiplatelet drugs. Rather, it compared two antiplatelet treatment strategies involving two different drugs. The specific design of the trial mandated routine pretreatment with ticagrelor in all patients but no pretreatment with prasugrel in patients who had acute coronary syndromes without ST-segment elevation.

Morning Report Questions

Q: How did ticagrelor compare to prasugrel regarding the risk of ischemic events in the trial by Schüpke et al.?

A: The authors had hypothesized that the ticagrelor-based strategy would be superior to the prasugrel-based strategy. An unexpected finding was that the risk of ischemic events in the trial was significantly lower in the prasugrel group than in the ticagrelor group. A primary end-point event — death from any cause, myocardial infarction, or stroke at 1 year after randomization — occurred in 184 of 2012 patients (9.1%) (Kaplan–Meier estimate at 1 year, 9.3%) in the ticagrelor group and 137 of 2006 patients (6.8%) (Kaplan–Meier estimate at 1 year, 6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P=0.006). The lower incidence of the composite end point was primarily driven by fewer myocardial infarctions in the prasugrel group than in the ticagrelor group.

Q: In the trial by Schüpke et al., was there a significant between-group difference in the risk of bleeding?

A: The benefit of fewer ischemic events with prasugrel did not occur at the expense of an increased risk of bleeding. In the modified intention-to-treat analysis (including all patients who received at least one dose of the randomly assigned trial drug and were assessed for bleeding events up to 7 days after discontinuation of the trial drug), major bleeding (Bleeding Academic Research Consortium [BARC] type 3 through 5) 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).

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