Prasugrel superior to ticagrelor in reducing ischaemic events in ACS + planned invasive strategy

Acute coronary syndrome (ACS) patients with or without ST-segment elevation who received treatment with prasugrel had significantly reduced rates of the composite endpoint of death, myocardial infarction, or stroke without an increase in major bleeding compared with ticagrelor treatment. These results from the ISAR-REACT 5 study were presented during a Hot Line Session on Sunday 1 Sept at ESC Congress 2019.

The ISAR‑REACT 5 trial is unique as it consisted of a head-to-head comparison of a ticagrelor vs prasugrel-based strategy in ACS patients with and without ST-segment elevation in terms of 1-year clinical outcomes [1]. “This was never done before; both drugs had only been compared with clopidogrel in ACS,” said Prof. Stefanie Schüpke (German Heart Centre Munich, Germany). The hypothesis of the trial was that ticagrelor would be superior to prasugrel in reducing the primary composite endpoint of death, myocardial infarction, or stroke within 12 months in ACS patients intended for an invasive strategy.

A total of 4,018 patients were randomised to receive either prasugrel or ticagrelor. As soon as possible after randomisation, patients allocated to ticagrelor received a loading dose. Prof. Schüpke said: “Timing of study drug administration was irrespective of clinical presentation and knowledge of coronary anatomy, while for those on prasugrel, timing of study drug initiation depended on clinical presentation. ST-elevation myocardial infarction (STEMI) patients received prasugrel as soon as possible after randomisation. In patients with acute coronary syndromes without ST-segment elevation (NSTE-ACS), administration of the prasugrel loading dose required knowledge of the coronary anatomy.”

The results were surprising as the primary composite endpoint at 12 months occurred in 9.3% of patients in the ticagrelor group and 6.9% in the prasugrel group. The incidence of death was 4.5% vs 3.7% for ticagrelor vs prasugrel, respectively. For MI, this was 4.8% vs 3.0%, 1.1% vs 1.0% for stroke, 1.3% vs 1.0% for definite or probable stent thrombosis, and 1.1% vs 0.6% for definite stent thrombosis, respectively. Bleeding (Bleeding Academic Research Consortium [BARC] type 3-5) occurred in 5.4% of patients on ticagrelor and 4.8% of patients who received prasugrel.

1. Schüpke S. ISAR-REACT 5 - Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome, FP Number 2306. ESC Congress 2019, 31 Aug-4 Sept, Paris, France.

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Posted on 10 October, 2019