Design and Rationale of Aspirin versus Aspirin and Fondaparinux Prior to Early Invasive Strategy in Patients with NSTEMI - The FOXY trial

BACKGROUND: Current guidelines recommend a combination therapy with aspirin and a parenteral anticoagulant in patients with non-ST-elevation myocardial infarction (NSTEMI) prior to invasive assessment. However, these recommendations are based on clinical trials conducted at a time when NSTEMI patients were not routinely assessed invasively. Today, nearly all NSTEMI patients in Denmark undergo coronary angiography within 72 hours, and the necessity of routine anticoagulation remains uncertain. The FOXY trial aims to assess whether aspirin alone is noninferior to a combination therapy with aspirin and fondaparinux in preventing death, recurrent myocardial infarction, and refractory ischemia while lowering the risk of bleeding.

TRIAL DESIGN: The FOXY trial is a multicenter, open-label, noninferiority, randomized controlled trial enrolling 5,076 patients with NSTEMI. Participants will be randomized 1:1 to receive either aspirin alone or aspirin plus fondaparinux before invasive evaluation. The primary endpoint is a composite of 30-day mortality, recurrent MI, and refractory ischemia. Secondary outcomes include long-term ischemic events, cerebrovascular accidents, left ventricular function, hospital length of stay, and major bleeding. The study will be conducted across multiple cardiology centers, with the first patients enrolled in spring 2025.

CONCLUSION AND PERSPECTIVE: The FOXY trial is the first study to investigate parenteral anticoagulant use in NSTEMI patients undergoing routine invasive management. By comparing aspirin alone to combination therapy, the study seeks to challenge current guideline recommendations and potentially simplify NSTEMI treatment. If noninferiority is demonstrated, the trial may support a shift toward a safer and more cost-effective management of NSTEMI patients. This could lead to a revision of clinical guidelines, minimizing bleeding risk, improving patient safety, and reducing healthcare costs.

TRIAL REGISTRATION: EU Trial Number: 2024-517229-18-00; ClinicalTrials.gov identifier: NCT06710184.