Best Endovascular versus Best Surgical Therapy in Patients with CLI (BEST-CLI) Trial: A Misleading Trial Name

The authors have read the recently published Best Endovascular versus Best Surgical Therapy in Patients with CLI (BEST-CLI) trial data (1Farber A. Menard M.T. Conte M.S. et al.Surgery or endovascular therapy for chronic limb-threatening ischemia.N Engl J Med. 2022; 387: 2305-2316Crossref PubMed Scopus (82) Google Scholar). Briefly, this randomized controlled trial compared surgical bypass with endovascular therapy between 2 cohorts of patients with chronic limb-threatening ischemia: Cohort 1 comprised patients with a suitable single segment of the great saphenous vein (SSGSV) for surgery and Cohort 2 comprised patients who did not have an SSGSV that could be used as a bypass conduit. Patients in each cohort were randomly assigned to surgical bypass or endovascular therapy. The study found that for patients in Cohort 1, bypass had fewer composite end point outcomes of major adverse limb events and mortality than those with endovascular revascularization. For patients in Cohort 2, bypass and endovascular therapies had similar outcomes. Although the authors of this letter commend the efforts of the trial’s authors, there are several concerning aspects of the study that must be recognized. The trial defined technical failure for endovascular therapy as the inability to cross a stenosis or occlusion or a residual obstruction of >50% in the superficial femoral artery, popliteal artery, and/or all tibial arteries such that there is no in-line flow. The failure rate of Cohort 1 was 15.3%, which is a higher incidence than that reported in contemporary data and similar to the results of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial conducted 17 years ago (2Iida O. Takahara M. Soga Y. et al.Three-year outcomes of surgical versus endovascular revascularization for critical limb ischemia: the SPINACH study (surgical reconstruction versus peripheral intervention in patients with critical limb ischemia).Circ Cardiovasc Interv. 2017; 10e005531Crossref PubMed Scopus (89) Google Scholar,3Adam D.J. Beard J.D. Cleveland T. et al.Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial.Lancet. 2005; 366: 1925-1934Abstract Full Text Full Text PDF PubMed Scopus (1655) Google Scholar). Has technology not evolved enough since the BASIL trial to enable better lesion crossing and revascularization? The primary endpoint of the trial was determined with an intention-to-treat analysis with inclusion of these unsuccessful endovascular procedures. Thus, the question of whether successful endovascular therapy is equivalent to or better than successful bypass remains unanswered. Reintervention in the endovascular group was the major driver of the composite endpoint. It is no surprise given the low rates of initial technical success that reintervention in the endovascular arm would be necessary soon after the index procedure. An astounding 42.5% of first reinterventions occurred within 30 days in the endovascular arm of Cohort 1. The early failure suggests vessel recoil or dissection rather than neointimal hyperplasia and is further evidence of suboptimal initial endovascular strategy. In the trial, 73% of endovascular procedures were performed by vascular surgeons, and patients were allowed to cross over to the bypass arm if endovascular techniques were unsuccessful. This could unintentionally result in a bias toward conversion to bypass for challenging endovascular procedures. Large series (4Siracuse J.J. Menard M.T. Eslami M.H. et al.Comparison of open and endovascular treatment of patients with critical limb ischemia in the Vascular Quality Initiative.J Vasc Surg. 2016; 63: 958-965.e1Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar) published in the literature have noted endovascular technical success rates to be >90%. Only a study conducted with equal representation of specialties performing endovascular procedures and without crossover between therapies could answer this question. Another shortcoming of the trial was the heterogeneity of the endovascular techniques employed. Among 708 patients in Cohort 1, 373 (52.7%) patients were treated with angioplasty alone. Only 52% of patients were treated with drug-coated balloons (197 [27.8%]) and/or drug-eluting stents (171 [24.2%]). The authors noted that a 2018 meta-analysis (5Katsanos K. Spiliopoulos S. Kitrou P. Krokidis M. Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials.J Am Heart Assoc. 2018; 7e011245Crossref PubMed Scopus (698) Google Scholar) reporting heightened mortality risk with paclitaxel-coated devices was published during the trial period and may have led to lower usage of these devices. However, enrollment for BEST-CLI began in 2014, several years after paclitaxel-coated devices were established as superior to plain balloons and noncoated stents for patients with peripheral arterial disease (6Cassese S. Byrne R.A. Ott I. et al.Paclitaxel-coated versus uncoated balloon angioplasty reduces target lesion revascularization in patients with femoropopliteal arterial disease: a meta-analysis of randomized trials.Circ Cardiovasc Interv. 2012; 5: 582-589Crossref PubMed Scopus (118) Google Scholar). Enrollment for the trial ended in 2019. By this time, most patients were enrolled before the suggestion of the paclitaxel safety risk. One could argue that these devices should have been universally used to represent the “best” endovascular therapy. Ultimately, the BEST-CLI trial compares the bypass technique with a myriad of different endovascular therapies chosen on the basis of operator preference without core laboratory adjudication—essentially, the best surgical option versus any, and often inferior, endovascular option. The fact that a suboptimal therapy can lead to a poorer composite endpoint is immediately reflected in Cohort 2 of the trial, which comprised patients requiring a prosthetic or alternative autogenous vein for bypass conduit. The BEST-CLI trial data suggested that patients with chronic limb-threatening ischemia should first undergo surgery if they have a suitable SSGSV for bypass. Unfortunately, the study was limited by suboptimal endovascular strategies, high endovascular failure rates, and heterogeneity among endovascular techniques employed. Hence, the conclusions of the authors of the BEST-CLI trial would only be accurate in centers where endovascular therapy has a high technical failure rate and endovascular treatment strategies are not based on the most current evidence.