Dual Antiplatelet Therapy Strategies After Acute Myocardial Infarction Undergoing PCI: Prasugrel vs Ticagrelor & 12 Months vs 1-3 Months

Acute myocardial infarction (MI) remains associated with a substantial risk of recurrent ischemic events after successful percutaneous coronary intervention (PCI). Current standard treatment after MI and PCI includes dual antiplatelet therapy (DAPT), usually aspirin plus a potent P2Y12 inhibitor, to reduce the risk of death, recurrent MI, stroke, and stent thrombosis. However, longer DAPT duration is associated with increased bleeding risk, and the optimal balance between ischemic protection and bleeding safety remains uncertain. In addition, although prasugrel and ticagrelor are both recommended after MI, comparative randomized evidence remains limited in contemporary MI populations treated with PCI.

STREAMLINE is a pragmatic, multinational, multicenter, investigator-initiated, prospective, randomized, controlled, open-label trial with blinded endpoint adjudication (PROBE design). The study is designed to evaluate antiplatelet treatment strategies in patients with acute MI who have undergone successful index PCI. Approximately 8,100 participants will be enrolled across 65 sites in 6 European countries.

The trial uses a 2×2 factorial design and addresses 2 main treatment questions. First, the study will assess whether an abbreviated DAPT strategy is non-inferior to a standard 12-month DAPT strategy for the prevention of ischemic events at 12 months. In the abbreviated strategy, participants receive 1 to 3 months of DAPT followed by potent P2Y12 inhibitor monotherapy for the remainder of the first year. In the standard strategy, participants receive 12 months of DAPT. Second, the study will assess whether a prasugrel-based strategy is superior to a ticagrelor-based strategy in reducing ischemic events without increasing bleeding.

Eligible participants are adults hospitalized with acute MI who undergo successful PCI and dot not have a recommendation for anticoagulant therapy (eg atrial fibrillation or metalic valvular prostheses)). Randomization is performed anytime after successful index PCI and hospital discharge. Participants are first randomized 1:1 to prasugrel- or ticagrelor-based treatment and then randomized 2:1 to abbreviated or standard DAPT. All other treatments are prescribed according to routine clinical practice and the judgment of the treating physician. After 12 months, ongoing antiplatelet treatment is left to the discretion of the treating physician.

The primary efficacy endpoint is the composite of all-cause death, non-fatal MI, or stroke at 12 months, analyzed as time to first event. For the abbreviated-versus-standard DAPT comparison, the study will test non-inferiority. For the prasugrel-versus-ticagrelor comparison, the study will test superiority. The main safety endpoint is major bleeding at 12 months, defined as Bleeding Academic Research Consortium (BARC) type 3a to 5 bleeding. Secondary endpoints include individual components of the primary composite, cardiovascular death, net clinical benefit, and unplanned revascularization.

Participants will be followed for 12 months. Mandatory follow-up assessments will occur at 3 and 12 months, with additional follow-up, when feasible, at 1, 6, and 9 months. Follow-up will be performed by telephone contact and review of medical records to assess survival, hospitalizations, recurrent ischemic events, bleeding events, and adherence to the assigned antiplatelet strategy. No protocol-mandated laboratory testing or electrocardiographic assessments are required beyond routine care.

Potential endpoint events will be documented using source medical records and adjudicated centrally by an independent Clinical Events Adjudication Committee blinded to treatment allocation. The trial is intended to provide clinically relevant evidence under real-world conditions and to inform future guideline recommendations regarding the optimal type and duration of antiplatelet therapy after acute MI treated with PCI.

Inclusion criteria

• ≥18 years old
• Admitted because of an acute MI (either STEMI or NSTEMI).
• Invasive management during index admission with successful PCI.
• Able to consent.

Exclusion criteria

• Indication for oral anticoagulation therapy.
• Intolerance, contraindication or known allergy to either aspirin, prasugrel or ticagrelor.
• Prior history of ischaemic or haemorrhagic stroke or transient ischaemic attack.
• Patients with active bleeding or known bleeding disorders.
• Patients with known moderate or severe hepatic dysfunction (Child-Pugh Class B or Class C).
• Known intracranial aneurism, arteriovenous malformation or neoplasm.
• Patients with chronic kidney disease requiring dialysis.
• Any disorder that may interfere with drug absorption.
• Pregnancy or current lactation.
• Concomitant use of potent CYP3A inhibitors or inducers.
• Planned elective surgery that cannot be deferred 12 months before randomization, requiring interruption of antiplatelet therapy.
• Any medical condition that, in the investigator´s judgment, would seriously limit life expectancy (less than one year)
• Active participation in other clinical trials.