European Society of Cardiology

European Society of Cardiology

Perspective from B. Hadley Wilson, MD, FACC
September 02, 2019
3 min read

ISAR-REACT 5: Prasugrel superior to ticagrelor in patients with ACS, planned invasive evaluation

Perspective from B. Hadley Wilson, MD, FACC
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PARIS — In patients with acute coronary syndromes, with or without ST-segment elevation, the rate of death, MI or stroke was significantly reduced at 1 year with prasugrel compared with ticagrelor, without an increase in major bleeding, according to a head-to-head comparison of both strategies.

The data are from the ISAR-REACT 5 trial, presented at the European Society of Cardiology Congress and published simultaneously in The New England Journal of Medicine.

The trial enrolled 4,018 patients with ACS for whom invasive evaluation was planned at 23 centers in Germany and Italy to evaluate outcomes at 1 year after a strategy of ticagrelor (Brilinta, AstraZeneca) or prasugrel (Effient, Daiichi Sankyo/Eli Lilly) antiplatelet therapy.

Death, MI or stroke at 1 year, the primary endpoint, occurred in 9.3% of patients assigned ticagrelor vs. 6.9% assigned prasugrel (HR = 1.36; 95% CI, 1.09-1.7; P = .006). Comparison of individual components of the primary outcome revealed similar results. The rate of death was 4.8% with ticagrelor vs. 3.7% with prasugrel (HR = 1.23; 95% CI, 0.91-1.68), MI was 4.8% vs. 3% (HR = 1.63; 95% CI, 1.18-2.25) and stroke was 1.1% vs. 1% (HR = 1.17; 95% CI, 0.63-2.15), according to results presented here.

The safety endpoint of major bleeding (BARC type 3 to 5) was similar and not significantly different between the two strategies, at 5.4% of the ticagrelor group vs. 4.8% in the prasugrel group (HR = 1.12; 95% CI, 0.83-1.51; P = .46).

Additionally, rates of definite or probable stent thrombosis were 1.3% in the ticagrelor group vs. 1% in the prasugrel group (HR = 1.3; 95% CI, 0.72-2.33).

At the start of the study, the ISAR-REACT 5 researchers hypothesized that ticagrelor would be superior to prasugrel for the primary composite endpoint in this population.

“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 researchers wrote in NEJM.

Patients in ISAR-REACT 5 had a mean age of 64 years and 23.8% were women. The primary diagnosis at time of admission was non-STEMI in 46% or STEMI in 41%. PCI was the treatment strategy in 84% of patients; the rest underwent CABG or received conservative therapy.

Patients assigned ticagrelor received a 180 mg loading dose starting as soon as possible after randomization, followed by a maintenance dose of 90 mg twice daily. Those assigned prasugrel received a 60 mg loading dose, followed by a maintenance dose of 10 mg once daily. The timing of prasugrel initiation was based on clinical presentation.


“The results of this trial support a prasugrel-based strategy, without routine pre-treatment in NSTEACS, as the first-line antiplatelet therapy for ACS patients,” Stefanie Schüpke, MD, from Deutsches Herzzentrum München in Munich, said during a press conference. – by Katie Kalvaitis


Schüpke S. Hot Line Session 2. Presented at: European Society of Cardiology Congress; Aug. 31-Sept. 4, 2019; Paris.

Schupke S, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1908973.

Disclosures: Schüpke reports she received support from the DZHK (German Center for Cardiovascular Research) for ISAR-REACT 5 and consulting fees from Bayer Vital GmbH.