The safety and efficacy of 'going long'.

In this issue of Vascular Medicine, Schroë and colleagues present the 12-month results of the long lesion cohort from the RANGER II Superficial Femoral Artery (SFA) Trial (ClinicalTrials.gov identifier: NCT03064126).1 This cohort is composed of patients who were in the original RANGER II SFA randomized controlled trial (RCT) plus the long balloon substudy, had a baseline lesion measurement > 100 mm, and were treated with a Ranger drug-coated balloon (DCB; Boston Scientific, Natick, MA, USA). This cohort contained symptomatic patients with Rutherford classification 2–4 disease. The major endpoints of the study included target lesion primary patency and freedom from major adverse events (MAEs) at 12 months. A secondary endpoint included changes in Rutherford classification. These are standard outcomes and are comparable to other studies in the field. Though small compared to many coronary interventional trials, a total of 129 patients met criteria for this cohort, which is comparable to many contemporary peripheral DCB trials.1 The mean lesion length was 144.5 ± 31.7 mm, which is more ‘real-world’ given that most RCTs in this vascular bed (SFA) limit lesion length to 80 mm.1 There were an impressive 32.6% total occlusions included, and calcification as graded by the Peripheral Arterial Calcium Scoring System (PACSS) was significant in 58.1% of the patients (grades 3 or 4), which is again illustrative of more ‘real-world’ contemporary SFA lesions. It is in the outcomes of this study where things diverge from other similar studies. Schroë and colleagues report a rather impressive primary patency in this study of 88% at 12 months with a very low adverse event rate of 4.9%, which was entirely accounted for by clinically driven target lesion revascularization (CD-TLR).1 To the interventionalist, outside of mortality, CD-TLR is the most important endpoint, as it reports how many patients needed to come back for repeat procedures – the bane of our existence in this vascular bed. A CD-TLR rate this low, as reported in this study, is unique given the length of lesions included. The most important outcome to report in any DCB trial in today’s climate is mortality, which in this study was very low at 2.4% (3/125) at 12 months.1 This is consistent with the 2019 study by Secemsky et al.2 and underscores the safety of this class of devices, though one might argue this is only 1-year data. In any DCB trial published after 2018, we must first focus on the safety profile of these devices. Most practicing in this field are aware of a controversial 2018 systematic review and meta-analysis performed by Katsanos et al.3 This analysis included 28 RCTs (total of 4663 patients) and identified an increased risk of death at 2 and 5 years posttreatment in patients treated with paclitaxel balloons and/or stents compared to the control arm.3 This study prompted the U.S. Food & Drug Administration (FDA) to release the following statement4: Based on the FDA’s review of available data and the Advisory Panel conclusions, the FDA recommend that health care providers consider the following recommendations: