Prasugrel versus Ticagrelor in Acute Coronary Syndromes

Whether prasugrel or ticagrelor should be the preferred P2Y12 inhibitor for patients with an acute coronary syndrome is uncertain.

We conducted a registry-based, open-label, stepped-wedge, cluster-randomized trial in Sweden involving adults who had undergone percutaneous coronary intervention for an acute coronary syndrome. Seven regions, grouped into three clusters, switched from ticagrelor to prasugrel as the default P2Y12 inhibitor in a randomized sequence across four 9-month periods between 2021 and 2024. The primary end point was a composite of death from any cause, fatal or nonfatal myocardial infarction, or fatal or nonfatal stroke through 1 year, as ascertained from national registries. In the intention-to-treat analysis, a mixed model adjusted for cluster and calendar time was used to obtain a policy-level estimate.

A total of 17,095 patients were enrolled; 9444 received care under the default ticagrelor policy, and 7651 received care under the default prasugrel policy. The mean (±SD) age of the patients was 69.8±11.5 years, and 36.8% were at least 75 years old; 27.8% of the patients were female. A total of 39.4% presented with ST-segment elevation myocardial infarction (STEMI), 43.7% with non-STEMI, and 16.8% with unstable angina. At 1 year, a primary end-point event had occurred in 11.8% of the patients in the ticagrelor-policy group and in 11.1% of those in the prasugrel-policy group (adjusted odds ratio [prasugrel vs. ticagrelor], 0.90; 95% confidence interval [CI], 0.77 to 1.06), and major bleeding had occurred in 4.4% and 4.2%, respectively (adjusted odds ratio, 0.80; 95% CI, 0.64 to 0.99).

In an unselected population of patients with an acute coronary syndrome who had undergone percutaneous coronary intervention, the risk of ischemic events was not lower with a default prasugrel policy than with a default ticagrelor policy. (Funded by Region Västra Götaland; SWITCH-SWEDEHEART ClinicalTrials.gov number, NCT05183178.).