In an effort to address the lack of data surrounding optimal treatment for patients with critical limb ischemia (CLI), the National Institutes of Health (NIH) has invested $25 million in the Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial. The NIH felt strongly that BEST-CLI must include all of the key stakeholders who currently treat CLI: vascular surgeons, interventional cardiologists, interventional radiologists, and vascular medicine specialists. The main differences between BEST-CLI trial and the Bypass vs. Angioplasty in Severe Ischemia of the Limb (BASIL) trial1 are that BEST-CLI is a a pragmatic trial fully incorporating current therapies, is meaningfully stratified by clinical and anatomic severity, and uses a primary endpoint (major adverse limb event-free survival) that is more sensitive to clinical failure.
The BEST-CLI trial also differs from the BASIL trial in design. The BEST-CLI trial is based on the premise that event rates are different for patients who have an expected bypass with a good-quality saphenous vein when compared with those who do not. It includes two independently powered, parallel trials comparing bypass and endovascular intervention in patients with adequate saphenous vein (N = 1,620) and those lacking adequate saphenous vein (N = 480), as determined by preoperative vein mapping. The design of the BEST-CLI trial is complex because it will include all types of interventions (eg, angioplasty, stenting, and atherectomy). Minimum follow-up is 2 years.
Currently, 112 sites have been selected for the BEST-CLI trial (Figure 1). Although the sites are dominated by vascular surgery investigators (n = 492), other specialties are also represented, including cardiologists (n = 155), radiologists (n = 113), and vascular medicine specialists (n = 2). Each site has a CLI team that includes all individuals who treat CLI at that particular site. The BEST-CLI trial defines specific criteria for both open reconstruction and below-the-knee intervention, which are required in order for the patient to be approached for inclusion in the study. Two physicians on each team must evaluate the patient’s case and confirm that the patient meets inclusion criteria and is therefore eligible for randomization. Two individual physicians on the team must also agree on the need for and the type of reintervention. The study was designed in this way as an acknowledgment that the type and timing of reintervention are both critical drivers of the trial endpoint. The trial also includes multiple measures of functional outcome and cost-effectiveness.
Not surprisingly, the BEST-CLI trial also has limitations, largely arising from the heterogeneity of patients and procedures that characterize current CLI practice. Despite its limitations, BEST-CLI represents a critical opportunity to collect high-quality, multicenter data from a randomized trial. Ultimately, more than one trial will be required to build a comprehensive evidence base in CLI.
The field of CLI treatment needs high-quality, randomized controlled trials and other comparative effectiveness studies. The BEST-CLI trial was designed to address many of the key limitations of the BASIL trial. BEST-CLI is a landmark trial that will define the current state of outcomes for interventions in CLI. In particular, quality of life and cost-effectiveness outcomes from BEST-CLI will be carefully scrutinized by managed care organizations. That said, no single trial can address all of the evidence gaps in the treatment of CLI. BEST-CLI must be followed by additional comparative studies.
Michael S. Conte, MD, is Chief of the Division of Vascular and Endovascular Surgery and Co-Director of the Heart and Vascular Center, University of California in San Francisco, California. He has disclosed that he has received compensation from Gore for participating in the Summit and has served as a consultant to Cook Medical and Medtronic Inc. Dr. Conte can be reached at [email protected]
- Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005;366:1925-1934.