Acute coronary syndrome (ACS) is a leading cardiovascular condition with high morbidity, mortality, and healthcare costs. STREAMLINE is a pragmatic, multicenter (66 sites across 6 countries), investigator initiated clinical trial designed to address key evidence gaps in antiplatelet therapy after ACS. Current guidelines recommend 12 months of dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor (prasugrel or ticagrelor) to prevent recurrent ischemic events, but this increases bleeding risk, especially in vulnerable populations such as the elderly.
This trial tests 2 main hypotheses:
1. An abbreviated DAPT strategy (3 months of aspirin+P2Y12 inhibitor followed by single antiplatelet therapy [SAPT] with a potent P2Y12i) is non-inferior to the standard 12 mo DAPT strategy in preventing recurrent ischemic events while significantly reducing bleeding.
2. A prasugrel-based abbreviated DAPT strategy is superior to a ticagrelor-based abbreviated DAPT strategy in reducing ischemic events without increasing bleeding.
The design of our trial will also allow us to test a prasugrel vs a ticagrelor based strategy regardless of the DATP duration. The trial will enroll 8,100 ACS patients across 6 European countries, ensuring representation of diverse populations and high-risk groups. Patients will undergo sequential randomization into 2 arms: 2:1 to abbreviated vs. standard DAPT, then 1:1 to prasugrel vs. ticagrelor within the abbreviated arm. The primary endpoint is the composite of death, non-fatal myocardial infarction, or stroke at 1 year, analyzed for non-inferiority (first hypothesis) and superiority (second). Major bleeding (BARC 3–5) is the key secondary outcome. This trial will generate robust, high-impact evidence to guide clinical practice, refine antiplatelet strategies, and improve outcomes, especially in vulnerable ACS patients. Findings will support guideline committees, policymakers, and clinicians in delivering safer, more effective care.