Design and Rationale of the Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST‐CLI) Trial

Critical limb ischemia (CLI) is a severe form of peripheral artery disease that leads to high rates of amputation and mortality. While both open surgical bypass and endovascular revascularization are commonly used to treat CLI, there is no consensus on which approach is superior for patients who are candidates for both. The BEST-CLI trial is a prospective, randomized, multicenter, superiority trial designed to provide Level I evidence to clarify the appropriate role for these two treatment strategies.

The study aims to enroll 2,100 patients across approximately 140 sites in the United States and Canada. The trial is divided into two cohorts based on the availability of a suitable single-segment saphenous vein for bypass. A key feature of the study is its pragmatic design: while patients are randomized to either an endovascular or surgical strategy, the specific procedural technique within that assigned approach is left to the discretion of the treating investigator, reflecting real-world clinical practice.

The primary efficacy endpoint is Major Adverse Limb Event (MALE)-free survival, a composite measure that captures limb-related morbidity and the need for major reinterventions. This endpoint was chosen because it more accurately reflects the clinical goals of CLI treatment—preserving a functional limb and avoiding repeat procedures—than traditional amputation-free survival metrics. Secondary endpoints include amputation-free survival, quality of life, functional outcomes, and cost-effectiveness.

Currently, treatment decisions for CLI are often driven by individual physician preference, training, and institutional bias rather than high-quality comparative evidence. By involving a multidisciplinary team of vascular surgeons, interventional cardiologists, and interventional radiologists, the BEST-CLI trial seeks to establish an evidence-based standard of care. The inclusion of comprehensive cost-effectiveness and quality-of-life analyses will further help healthcare systems optimize the allocation of resources for this high-risk patient population.