RCT: In patients with ACS, prasugrel vs ticagrelor reduced a composite of death, MI, or stroke at 1 y; groups did not differ for major bleeding.
Schupke S, Neumann FJ, Menichelli M, et al. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 Oct 17;381(16):1524-1534. doi: 10.1056/NEJMoa1908973. Epub 2019 Sep 1.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain.

METHODS: In this multicenter, randomized, open-label trial, we 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.

RESULTS: 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%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. 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).

CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Ratings
Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Cardiology
Intensivist/Critical Care
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Emergency Medicine
Comments from MORE raters

Cardiology

This article is difficult to assess: 233 were excluded from analysis in one arm and 3 in the other. Different protocols were used for each agent. Hard to believe that an editorial was not included.

Emergency Medicine

In my institution as an emergency medicine doctor, I don't have influence on the discharge medication after a patient presents with ACS. Cardiologists also dictate pre-cath medications. So, this is interesting, but not relevant to EM.

The choice of antiplatelet agent in ACS probably matters. However, in the current era of rush to cath lab (30-minute window for ED-door-to-cath-lab time, 90-minute window for ED-door-to-balloon time), little opportunity exists to meaningfully converse with cardiologists about the NNT/NNH of specific antiplatelet agents. Few cardiologists wish to discuss the nuances of antiplatelet choice during off-hours when not in door-to-cath-lab rush, and time to converse during ACS episode is non-existent. Each cardiologist seems to have preferences and those preferences do not consistently align with evidence. Based on this non-industry-sponsored trial, prasugrel appears to be a superior choice to reduce the composite outcome and avoid bleeding complications.

Family Medicine (FM)/General Practice (GP)

Although primary care does not make the decision of what to pick, we often deal with the follow-up, so this is good to know.

General Internal Medicine-Primary Care(US)

This is mainly relevant for cardiologists who manage ACS.

Internal Medicine

A surprise finding that :”... the present trial shows that a prasugrel-based strategy with deferred loading after knowledge of coronary anatomy in patients with acute coro- nary syndromes without ST-segment elevation was superior to a ticagrelor-based strategy with routine pretreatment.” This will challenge many widely held ‘reasonable‘ assumptions and should influence care decisions both during the immediate ACS care AND the ongoing care, including primary care, of these patients for at least the 1 year that follows.

Comments from JournalWise subscribers
Dr. Stots Reele on 2019-09-18
An example where pharmacology probably makes a difference. Prasugrel is a non-reversible platelet inhibitor, so the effect is still present if a patient misses some doses. Ticagrelor is a reversible inhibitor, so there would be no antiplatelet inhibition with missed doses.
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