Trial Update: Peripheral Vascular Disease

November 22, 2017 | Erica Flores, MD

The age-old question of surgery versus endovascular treatment of cardiovascular disease has been studied in the coronaries and the carotids. However, there has been only been one major previous study for peripheral arterial disease (PAD), and the endovascular treatment was limited to angioplasty. The BEST-CLI trial is a prospective, randomized, controlled superiority trial with over 140 sites that began in 2014. It is designed to determine which treatment is superior for critical limb ischemia and thus define the standard of care for this patient population. The principal investigators of the trial include Matthew Menard, MD; Kenneth Rosenfield, MD, FACC; and Alik Farber, MD. Menard is a vascular surgeon at the Brigham and Women's Hospital, and co-director of the Endovascular Surgery Program Director and the Vascular and Endovascular Surgical Fellowship. Rosenfield is the section head of Vascular Medicine and Intervention Division of Cardiology at Massachusetts General Hospital. He is also the prior chairman of the peripheral vascular disease (PVD) committee and has served on the writing committee for ACC/AHA PAD guidelines. Farber is the chief of vascular and endovascular surgery at Boston University School of Medicine and co-director of the vascular non-invasive vascular laboratory. The three co-investigators answered several questions regarding the trial.

1. Do you think the study will allow us to come up with a scoring system to predict which patients would benefit from surgery over endovascular treatment?

This study is in some ways the holy grail of clinical research for PVD patients. The development of a practical and versatile scoring system that would reliably predict the relative benefit of surgery versus endovascular therapy for a given patient remains a clear unmet challenge to date. I have been impressed with some of the efforts in this regard for coronary interventions, based on the results of recent randomized control trials. I think we all recognize the need for a more sophisticated understanding of the relevant clinical domains that contribute to overall outcome for a given patient, specifically individual patient-related risk factors, wound-related factors and anatomy. Certainly, WiFI represents a much-needed advance in wound classification over the Rutherford system, and is an important component of BEST-CLI. Several validated patient risk classification schemes currently exist, and new systems are being developed for the challenging anatomic component that attempt to move beyond TASC. It is our hope that BEST-CLI will afford an opportunity to clarify utility in each of these important clinical areas, ideally resulting in a comprehensive scoring system that proves useful to all who care for CLI patients.

2. Given that the study was originally designed with the Rutherford class system, and now the WiFI classification scheme is also being used, do you think this will result in difficulty in terms of interpreting the results?

From its inception, BEST-CLI has always incorporated not only the Rutherford system, but also the WiFI system and Wagner wound classification scheme. As such, it should afford a unique opportunity to examine the differences in predictive power of each system, and again, to potentially further validate the WiFI system over and above what has been done to date. Our hope is to be able to draw definitive conclusions as to the utility of each system (given the enormous impact of wounds and wound-related care on cost) quality of life and overall outcomes in complex CLI patients.

3. Are there any preliminary results that you are willing to share?

At present, we remain blinded to any clinical outcomes of the trial. I can tell you that trial compliance has been excellent, with low crossover rates and low rates of lost to follow-up. I can also comment that our percentage of women and minority status patients at present closely matches our pre-launch predictions and what was expected by the National Institute of Health, and that the demographics and clinical criteria of enrolled patients reflect a typical cohort of CLI patients. I can further share that we have looked closely at who is actively enrolling in the trial, with the goal of determining how representative we are compared to who is treating CLI here in the United States. Rick Powell, who chairs our credentialing committee, recently found a very close match between the breakdown of CLI care by specialty within the Medicare claims database and who is treating CLI within BEST-CLI. This data was recently presented at the New England Society of Vascular Surgery annual meeting.

4. Have you received any feedback regarding an increase in the use of multidisciplinary rounding on CLI patients due to the study?

My co-principal investigators, Kenneth Rosenfield, MD, FACC, and Alik Farber, MD, and I believed it was critically important to include all practitioners who care for CLI patients in North America within BEST-CLI, and we have been pleased to the degree we have been able to achieve inter-disciplinary collaboration within the trial. Over 80 percent of sites are multi-disciplinary, meaning that the participating institution's "CLI team" includes interventional cardiologists, interventional radiologists and vascular medicine specialists partnering with their vascular surgery colleagues. We have many sites that have remarked on how the trial has transformed the way CLI patients are managed at their hospital. Specifically, investigators from both surgical and non-surgical subspecialties are coming together on a weekly or as-needed basis. This affords the opportunity for the entire group to review all presenting CLI patients, evaluate their diagnostic imaging, efficiently obtain any appropriate additional testing (e.g. vein mapping) and collectively determine appropriateness for BEST-CLI. At many of these sites, there was little to no such collaboration preceding the trial. The development of these collaborative care teams is like those seen in advanced multi-disciplinary cancer care, and has parallels in the successful "heart team" models developed for TAVR programs and complex CAD care. Although not the primary objective of the trial, at the end of the day, such teamwork – both within and between relevant specialties – best allows the collective expertise of each institution to be focused appropriately on deciding the optimal therapeutic option for each individual CLI patient.

This article was authored by Erica Flores, MD, FIT at Banner Medical Center in Phoenix, AZ.