Lutonix BTK Studies: Below-the-Knee Challenges Linger

LEIPZIG, GERMANY—Fresh data presented here from two studies of a drug-coated balloon (DCB) for below-the-knee (BTK) atherosclerotic lesions show some promising efficacy and safety out to 1 and 2 years, but compared with plain old balloon angioplasty (POBA) there are signs that operators still battle a steep learning curve to obtain lasting patency.

The 440-patient multicenter randomized Lutonix BTK IDE trial pitted the paclitaxel-based Lutonix 014 DCB (BD) against POBA in BTK patients with primarily Rutherford class 4 and class 5 critical limb ischemia (CLI). In the 6-month results, presented at VIVA 2018, the efficacy endpoint (composite of freedom from above-ankle amputation, target-lesion occlusion, and clinically driven TLR) was higher in the DCB arm compared with percutaneous transluminal angioplasty at 85.8% vs 71.4% (P < 0.001).

In the 1-year results, presented here at LINC 2020 by Patrick Geraghty, MD (Washington University Medical School, St. Louis, MO), there was no longer a statistical difference in the efficacy endpoint: 60.3% for DCB and 60.9% for POBA (P = 0.54). As Geraghty showed, the plot points for DCB and POBA, which gave the advantage to DCB at 6 months, had come back nearly together by 1 year. There also was no difference in the rate of cumulative TLR between the DCB and POBA (17.8% vs 21.8%; P = 0.39) and no difference in the percentage of patients with wounds, with the wound rate decreasing in both groups over time from baseline.

Geraghty said safety analyses, which have been done on approximately three-quarters of the cohort, show no differences between the DCB and POBA groups in freedom from all-cause death, freedom from major amputation, and amputation-free survival.

Balloon Diameter and IVUS Figure Prominently in Success

Despite the tapering off of advantage for the DCB at 1 year, a co-investigator for Lutonix BTK IDE told TCTMD he remains optimistic.

Jihad A. Mustapha, MD (Advanced Cardiac & Vascular Centers for Amputation Prevention, Lansing, MI), said technical issues, primarily undersizing of the balloon, are likely responsible for the loss of advantage to POBA. Noting that most of the restenosis that occurred was in the form of focal occlusions in different areas of the target lesion, he said it makes sense that there was a lack of complete contact between the balloon and the vessel wall in many cases in the RCT that led to premature patency problems.

Adding that the learning curve for gaining good patency results in BTK lesions with DCBs is only just beginning to be fully understood, Mustapha pointed to work by Francesco Liistro, MD (San Donato Hospital, Arezzo, Italy), who presented data in the same session on optimizing vessel treatment in BTK disease. Liistro maintained that the addition of ultrasound can reduce sizing problems and showed examples to illustrate the added value of it over angiography alone.

Drug-coated balloons for tibial arteries will prevail—they will be successful, once we use them properly. Jihad Mustapha

“We need to step up to the plate and start sizing appropriately and use the IVUS,” Mustapha continued, noting that many of his peers who are “eyeballing” vessel size are doing it wrong. “Drug-coated balloons for tibial arteries will prevail—they will be successful, once we use them properly.” He said payers need to support the use of added imaging in these procedures, adding that for many patients the interventions may not just save their limbs but also their lives.

In August 2019, the US Food and Drug Administration rejected a submission for approval of the Lutonix 014 DCB for use in BTK disease. Mustapha said while he understands the agency’s position, he is hopeful that they will eventually approve the device and also mandate that it only be used with appropriate vessel prep and imaging.

Registry Confirms Long-term Safety

In a separate presentation, session moderator Dierk Scheinert, MD (University Hospital Leipzig, Germany), showed 24-month data from the BTK Registry on 371 patients from 26 centers across Europe who received Lutonix 014 DCBs.

“The total target lesion length was 12 cm on average, which I think is showing that this is a real-world population and far beyond the typical short lesions which are otherwise studied in randomized trials,” Scheinert noted.

At 24 months, freedom from primary safety events (a composite of all-cause death, above-ankle amputation, or major reintervention) was 90.7% and freedom from TLR was 78.9%. These results, Scheinert said, reinforce “that this treatment was really safe in the hands of these operators.”

Analyzing the secondary endpoints separately, freedom from major amputation was 93.4% and freedom from reintervention for thrombosis/thrombolysis was 89.1%. The entire cohort remained free from reintervention for either distal embolization or unexpected device/drug-related events. Additionally, freedom from all-cause death was 80.5%.

The endpoints of all-cause death and major amputation have recently become an issue with the publication of a meta-analysis suggesting increased rates of both in patients treated for BTK lesions with a paclitaxel balloon compared with POBA in several RCTs.

Scheinert concluded by noting that the registry patients experienced significant shifts in Rutherford classification by 24 months, with 81.9% improving by at least one category and almost 60% improving by 3 categories or more. Only 17% of patients had no change in Rutherford category and only 1.4% (2 patients) had worsening.