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July 11, 2021
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ISAR-REACT 5: Prasugrel outperforms ticagrelor in PCI-treated patients with ACS

New research from the ISAR-REACT 5 trial indicated that patients with ACS who received PCI had a lower composite endpoint of all-cause death, MI or stroke when given prasugrel vs. ticagrelor therapy.

Bleeding events were similar between the groups.

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As previously reported by Healio, ISAR-REACT 5 showed superior outcomes for prasugrel (Effient, Daiichi Sankyo/Eli Lilly) compared with ticagrelor (Brilinta, AstraZeneca) among patients with ACS and planned invasive evaluation. In the present analysis, J. J. Coughlan, MB, BCh, interventional research fellow at Deutsches Herzzentrum München, Technische Universitat Munchen in Munich, and colleagues aimed to determine the safety and efficacy of both therapies in a subgroup of patients who actually underwent PCI. The subgroup included 3,377 patients who were randomly assigned to a ticagrelor-based or prasugrel-based strategy.

According to results, the primary endpoint — a composite of all-cause death, MI or stroke at 12 months — was elevated with ticagrelor treatment compared with prasugrel treatment (9.8% vs. 7.1%; HR = 1.41; 95% CI, 1.11-1.78; P = .005). The disparity was largely driven by a higher incidence of MI with ticagrelor (5.3% vs. 3.8%; HR = 1.67; 95% CI, 1.19-2.34; P = .003), the researchers wrote.

Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding, the study’s safety endpoint, did not differ between treatment strategies (ticagrelor, 5.3%; prasugrel, 4.9%; HR = 1.1; 95% CI, 0.81-1.5; P = .54).

“Overall, these data support the preference for a prasugrel-based strategy vs. a ticagrelor-based strategy in patients presenting with ACS who are treated with PCI,” the researchers wrote. “Because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis-generating and dedicated randomized clinical trials may be warranted to confirm these findings.”

Ajay J. Kirtane

In an accompanying editorial, Ajay J. Kirtane, MD, SM, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and interventional cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center, wrote that the new data are consistent with the primary study results of ISAR-REACT 5, which were unexpected and in contradistinction to the initial study hypothesis.

“Based on prior data, the study investigators had hypothesized that the ticagrelor-based strategy would be superior to the prasugrel-based one, but the opposite result was demonstrated, a finding that was also reflected in the postrandomization PCI subgroup,” Kirtane wrote. “Although surprising, the editors felt that these findings were important as they support the main trial results and once again emphasize the essential importance of conducting head-to-head trials of pharmacologic strategies for patients with ACS.”

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