Key takeaways
A potent P2Y12 inhibitor plus aspirin is recommended in patients with acute coronary syndromes who have undergone coronary stenting.
Switching from ticagrelor to prasugrel as the default P2Y12 inhibitor was evaluated in the large registry-based randomised SWITCH SWEDEHEART trial.
Prasugrel and ticagrelor were comparable for major cardiovascular events, but prasugrel was associated with lower major bleeding.
Post-approval randomised trials run inside national registries can answer real-world questions about approved treatments quickly with low trial costs.
Munich, Germany – 29 August 2026: Prasugrel reduced major cardiovascular events to the same extent as ticagrelor but with lower major bleeding after coronary stenting in patients with acute coronary syndromes, according to results from the SWITCH SWEDEHEART trial presented in a Hot Line session today at ESC Congress 20261 and published simultaneously in the New England Journal of Medicine.
A potent P2Y12 inhibitor plus aspirin is the standard of care to prevent major cardiovascular events in patients with acute coronary syndromes (ACS) who have undergone percutaneous coronary intervention (PCI).2
The relative merits of two potent P2Y12 inhibitors – prasugrel and ticagrelor – have been widely debated, noted Principal Investigator of SWITCH SWEDEHEART, Professor Elmir Omerovic from Sahlgrenska University Hospital, Gothenburg, Sweden: "In the ISAR-REACT 5 trial, a prasugrel-based strategy was superior to a ticagrelor-based strategy for major cardiovascular events without an increase in major bleeding,3 but whether the same difference would be seen in an unselected population in everyday clinical practice was unknown," he explained, continuing, "Several Swedish healthcare regions decided to adopt prasugrel as the default P2Y12 inhibitor for ACS and we used this change as the basis for a pragmatic evaluation of a default prasugrel policy compared with ticagrelor using the established SWEDEHEART registry platform." The 2023 ESC Guidelines already state that prasugrel should be considered in preference to ticagrelor for ACS patients who undergo PCI (class IIa, Level B).2 SWITCH SWEDEHEART adds pragmatic, registry-based randomised evidence in an unselected population.
The registry-based SWITCH SWEDEHEART trial randomised regions rather than individual patients: seven Swedish regions in three clusters switched their default P2Y12 inhibitor from ticagrelor to prasugrel at staggered, randomly assigned times (a stepped-wedge design).
The trial included all 17,095 consecutive adults with ACS undergoing PCI, including elderly patients and those with prior stroke or an indication for oral anticoagulation, who are usually excluded from trials. Under the ticagrelor policy, 9,444 patients were recommended to receive ticagrelor 90 mg twice daily. Under the prasugrel policy, 7,651 patients were recommended to receive prasugrel 10 mg once daily reduced to 5 mg once daily in patients aged 75 years or older, or weighing less than 60 kg, as per the label.
The primary endpoint of death from any cause, myocardial infarction or stroke at one year occurred in similar proportions of patients with each treatment policy: 11.1% of patients under the prasugrel policy and 11.8% under the ticagrelor policy (adjusted odds ratio [OR] 0.90; 95% confidence interval [CI] 0.77 to 1.06). The individual components of the primary endpoint did not differ.
Of note, the risk of major bleeding at one year was significantly lower with the prasugrel policy compared with the ticagrelor policy (4.2% vs. 4.4%; OR 0.80; 95% CI 0.64 to 0.99).
Commenting on the first of SWITCH SWEDEHEART's main conclusions, Professor Omerovic said: "In the largest randomised comparison to date, prasugrel offered comparable protection against major cardiovascular events, but with a signal toward less bleeding and lower cost – a potentially important consideration for patients and healthcare systems." Secondly, he noted the success of the novel methodology: "We were able to run a large policy-level, randomised trial within a national registry at a fraction of the cost of a conventional trial, evaluating the impact of two treatments and an important healthcare change in real-world patients. Our trial represents a model of clinical evidence generation that could be used to great effect across cardiology and in many other areas of healthcare."
