Following BEST-CLI and BASIL-2, Do We Better Understand How to “Best” Serve Critical Limb Threatening Ischemia Patients?
Jos C. van den Berg, MD, PhD1; Barry T. Katzen, MD2; Walter Dorigo, MD3; Andrew Holden, MD4; Daniella Kadian-Dodov, MD5; Robert Lookstein, MD6; Jihad A. Mustapha, MD7; John H. Rundback, MD8; Thomas Zeller, MD9
*On behalf of the Critical Limb Ischemia Global Society Board of Directors
Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease (PAD) including ischemic pain, ulcerations, and/or gangrene representing a major medical and socioeconomic burden on health and social care services worldwide.1 Recently, 2 randomized controlled landmark trials (RCT), the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI)2 and BASIL-2 (Bypass versus Angioplasty for Severe Ischemia of the Leg)3 studies, were published investigating patient and limb-related outcomes of participants with CLTI who underwent endovascular versus open-surgical treatment. In the BEST-CLI study uniquely, patients were divided into 2 cohorts, those with a single segment of adequate greater saphenous vein for bypass (cohort 1), and those without (cohort 2). Randomization included stratification by clinical presentation (Rutherford-Becker category 4 vs 5/6) and the presence vs absence of significant tibial disease. BASIL-2 compared the clinical effectiveness of a “vein bypass first” or a “best endovascular treatment first” strategy for revascularization of severe ischemia due to infrapopliteal arterial disease. Correction of additional proximal inflow disease was allowed prior to infrapopliteal revascularization.
Since there was a striking paucity of high-level comparative effectiveness evidence on the optimal treatment of patients with CLTI so far, both these landmark trials were awaited with great interest. However, study outcomes are conflicting and therefore worthy of intensive review and in-depth analysis for all medical professions confronted with such patients.
What are the primary endpoint outcomes?
In BASIL-2, after a minimum follow-up of 2 years, the primary outcome (major amputation or death) occurred in 63% of the bypass group and 53% of the best endovascular group, with an adjusted hazard ratio of 1.35 (95% confidence interval CI 1.02-1.80, P=.037), in favor of best endovascular treatment. The mortality difference continues throughout the trial rather than only during the peri-operative period, whereas there was no difference in amputation rates.
In BEST-CLI, in cohort 1 at a median 2.7 years of follow-up, a primary outcome event (major adverse limb event or all-cause mortality) occurred in 42.6% in the bypass group and in 57.4% in the endovascular group, hazard ratio 0.68 (95% CI .59-.79; P<.001). There were significantly more re-interventions in the endovascular group, and a significantly reduced rate of major amputations with bypass surgery. In cohort 2, a primary outcome event occurred in 42.8% in the surgical group and in 47.7% in the endovascular group, hazard ratio 0.79 (95% CI .58-1.06; P=.12) after a median follow-up of 1.6 years. Adverse event rates were similar in both cohorts.
What are similarities between BASIL-2 and BEST-CLI?
Both are prospective randomized controlled studies comparing the safety and effectiveness of bypass surgery with use of an optimal vein and “best” endovascular therapy in patients suffering from critical limb threatening ischemia (CLTI) using a pragmatic approach leaving in particular the decision of best endovascular therapy to the discretion of the operator. The second similarity is that both studies were terminated early due to slow enrollment and termination of funding.