В Швеции доказано, что прасугрел не превосходит тикагрелор в профилактике сердечно-сосудистых событий

MUNICH — In the SWITCH-SWEDEHEART trial of more than 17,000 patients with acute coronary syndrome (ACS), prasugrel did not appear superior to ticagrelor for preventing major cardiovascular events. Although bleeding rates were lower during the periods when patients were treated with a prasugrel-first policy, “protection against major events was similar with both strategies in this unselected population,” said principal investigator Elmir Omerovic, MD, PhD, a professor of cardiology at Sahlgrenska Hospital, University of Gothenburg, in Gothenburg, Sweden. “Recommending prasugrel first did not result in a significant further reduction in death, heart attack, or stroke,” Omerovic said. The results of this open-label, stepped-wedge, cluster-randomized trial, called were presented at the European Society of Cardiology (ESC) Congress 2026 and simultaneously published in The New England Journal of Medicine. Prasugrel vs Ticagrelor as Default Treatment Policies The SWITCH SWEDEHEART trial was designed to compare a default policy of prasugrel vs ticagrelor when either is offered with aspirin for dual antiplatelet therapy (DAPT) in ACS. Researchers intended to gather data for recommending one therapy over the other as a national policy in Sweden. For the study, seven Swedish administrative regions were grouped into three clusters. In the first of four 9-month study periods, all patients were managed with a ticagrelor-default policy. At the end of the first period, cluster 1 crossed over to a prasugrel-default policy while ticagrelor remained the default in the other clusters. Clusters 2 and 3 crossed over during subsequent periods until the last period when all patients in all clusters were being managed with a prasugrel-default policy.  The trial also included two prospectively defined blanking periods — January to March 2023 due to a national prasugrel supply shortage and November 2023 due to a regulatory delay. Researchers excluded observations from these periods from the primary analysis.  Ultimately, researchers enrolled 17,095 patients aged 18 years or older with an ACS during an index hospitalization. There were no exclusions, including for history of a prior stroke, need for anticoagulants, or advanced age. The mean age was 70 years, and 36.8% were 75 years or older.  Of patients enrolled, 43.7% had a non-ST-segment elevation myocardial infarction (NSTEMI), 39.4% had a STEMI, and 16.8% had unstable angina, Omerovic reported. After 1 year of follow-up, a major adverse cardiovascular event (MACE), defined as death from any cause, fatal or nonfatal myocardial infarction, or fatal or nonfatal stroke, had occurred in 11.8% of patients managed on a ticagrelor-default policy and 11.1% of those managed on a prasugrel-default policy. The result favored prasugrel but was not statistically significant (adjusted odds ratio [OR], 0.90; P  =.22). A Difference in Major Bleeding When analyzed separately, none of the components of the primary endpoint and none of the other secondary endpoints, such as stent thrombosis, showed a significant advantage for prasugrel management, with the exception of major bleeding. The modestly lower rate of major bleeding on prasugrel (4.2% vs 4.4%) produced a favorable 20% reduction in likelihood that just reached statistical significance (OR, 0.80; 95% CI, 0.64-0.99). Even though the data did not support the study hypothesis of a lower risk for MACE with a prasugrel-default policy, Omerovic’s interpretation was that “with equal protection against major events and less major bleeding the overall balance favors prasugrel” as a first choice in routine care. This interpretation was not uniformly shared, according to several commentators, including Robert A. Byrne, MB, BCh, PhD, who wrote an editorial accompanying the study’s publication in NEJM. He praised the trial’s design to address an almost 20-year-old controversy but also highlighted limitations.  For one, only 61% of those treated under a prasugrel-first policy vs 76% of those under a ticagrelor-first policy received their assigned P2Y12 inhibitor. Most patients who did not receive their assigned drug received clopidogrel, which is associated with a lower bleeding risk. He also pointed out that patients were enrolled without informed consent, a decision that was challenged by the Swedish Medical Products Agency early in the course of the trial but was ultimately dismissed by the Swedish Administrative Court of Appeals. Although he considered the all-comers design a strength, he predicted this controversy might continue to be a source of debate as the results are evaluated. The multicenter randomized TRITON-TIMI 38 and PLATO trials of prasugrel in 2007 and ticagrelor in 2009, respectively, marked the start of the long-time duel between high potency antiplatelet agents. Both were found superior to clopidogrel for a composite of MACEs when each was combined with aspirin for DAPT in patients with ACS. For ACS, the 2019 ISAR-REACT-5 trial has been the only major multicenter, controlled study to compare the two directly. But this study had important exclusions, such as prior stroke or need for oral anticoagulants. These exclusions and the randomization of a younger population made the trial’s “generalizability to routine practice uncertain,” Omerovic said while explaining the rationale for the SWITCH-SWEDEHEART trial. On the basis of ISAR-REACT-5 trial, ESC guidelines identified prasugrel as a preferred P2Y12 component of DAPT since 2023. However, the 2025 joint guidelines from the American College of Cardiology and American Heart Association identify both as class 1 options with no preference. Roxana Mehran, MD, a professor of medicine and director of Interventional Cardiovascular Research and Clinical Trials at the Icahn School of Medicine at Mount Sinai, New York City, strongly praised the design and size of this trial to answer a persistent question, but she is not certain that it did so. “Either agent remains a defensible regional default. In an unselected PCI population the trial does not separate them,” said Mehran, who served as a discussant for the trial. Despite pointing out limitations of the SWITCH-SWEDEHEART trial, including the potential effect of a higher substitution of clopidogrel in the prasugrel arm, Mehran admired the trial. She maintained that these are the types of large, real-world practice trials needed if one of these high potency P2Y12 inhibitors is ever established as the default. Omerovic reported having no potential conflicts of interest. Byrne reported having financial relationships with Abbott Vascular, Boston Scientific, Teleflex, and Terumo. Mehran reported having financial relationships with Abbott, Alleviant, Chiesi, Concept, Cordis, CPC Clinical Research, Daiichi Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medtronic, New Amsterdam, Novartis, Novo-Nordisk, Protembis, Radcliffe, and Sanofi. Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including cardiology, for several decades.