"The ISAR-REACT 5 trial (https://bit.ly/2UDEN4N) has demonstrated the superiority of prasugrel to ticagrelor for patients presenting with ACS," said Dr. J. J. Coughlan of the Technical University of Munich, in Germany.
"This current study, analyzing outcomes in patients treated with PCI is important for two main reasons," he told Reuters Health by email. "Firstly, PCI is the most frequent treatment strategy for patients with ACS. Secondly, in ACS patients treated with PCI, it has been assumed that pre-treatment with a P2Y12 inhibitor may play an important role. The initial ISAR-REACT 5 study hypothesis, which assumed the superiority of ticagrelor to prasugrel, was based on this paradigm."
Ticagrelor and prasugrel are both potent inhibitors of the P2Y12 receptor, but their drug class and mechanism of action are different, Dr. Coughlan and colleagues observe in JAMA Cardiology.
The new analysis included more than 3,300 patients, most of whom were men, with 1,676 in the ticagrelor arm and 1,701 in the prasugrel arm. The primary endpoint - a composite of all-cause death, myocardial infarction, or stroke at 12 months - was reached in 9.8% in the former group and 7.1% in the latter (hazard ratio, 1.41; P=0.005).
As Dr. Coughlan pointed out, "it was thought that pre-treatment in the ticagrelor arm in ISAR-REACT 5 might result in superior outcomes compared to the prasugrel arm. The group of patients treated with PCI was the treatment group in which it was felt that this pre-treatment may have been most important."
"The current analysis," which shows the initial hypothesis was incorrect, "helps to guide the optimal anti-platelet strategy for the most common management strategy for patients with ACS (PCI), both in terms of the choice of anti-platelet agent and the value of pre-treatment," the researcher said. "Overall, our findings suggest that for patients presenting with ACS who undergo PCI, a prasugrel-based strategy initiated at the time of the procedure is superior to a ticagrelor-based pre-treatment strategy."
The author of an accompanying editorial, Dr. Ajay J. Kirtane of Columbia University Irving Medical Center/New York-Presbyterian Hospital, in New York City, told Reuters Health by email that "the findings of this analysis are consistent with the primary study results of ISAR-REACT 5, which were unexpected."
And, he added, "as well as supporting the main trial results, the findings once again emphasize the essential importance of conducting head-to-head trials of pharmacologic strategies for patients with ACS."
SOURCE: https://bit.ly/3xrJBc4 and https://bit.ly/2UrjZxu JAMA Cardiology, online June 30, 2021.
By David Douglas
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