The DEFINITIVE LE (Determination of effectiveness of SilverHawk / TurboHawk peripheral plaque excision systems for the treatment of infrainguinal vessels/lower extremities) clinical trial is the largest peripheral atherectomy study conducted to date with independent physician review of the outcomes. The study enrolled 800 patients at 47 centres in the USA and Europe.
“For the first time, the DEFINITIVE LE study has provided robust evidence within a large and diverse PAD patient population,” said Lawrence A Garcia, chief of Interventional Cardiology and Vascular Interventions at St Elizabeth’s Medical Center in Boston,USA. “Directional atherectomy, with the SilverHawk and TurboHawk devices, delivers patency results at 12 months post-treatment that are comparable to those reported in stent studies—and with the important advantage of not leaving anything behind in the vessel.”
DEFINITIVE LE 12-month efficacy and safety results
Clinical outcomes were improved by 30 days and sustained through 12 months of follow-up. Directional atherectomy with the SilverHawk and TurboHawk devices delivered 12-month patency results that were comparable to those reported in stent studies.
Among patients with claudication, primary patency (i.e., the treated artery remained open) was 78% using a peak systolic velocity ratio (PSVR) < 2.4 at 12 months. Notably, this rate did not differ between patients with diabetes (77%) and those without diabetes (78%)—the first such results to be shown in a prospective, powered analysis. Among patients with critical limb ischaemia, 95% were able to avoid a major unplanned amputation of the target limb. The SilverHawk and TurboHawk devices were shown to have a strong safety profile in the study, with low complication rates.
“DEFINITIVE LE confirmed equivalent outcomes between diabetics and non-diabetics in terms of patency and persistent clinical improvement up to 12 months after treatment,” said Thomas Zeller, head of the Department of Angiology at Universitäts-Herzzentrum Freiburg-Bad Kronzingen, Bad Krozingen, Germany. “Because diabetics have more advanced PAD, re-stenose faster and are more difficult to treat than non-diabetics, it is critical to preserve future treatment options in this patient population. The confirmation from DEFINITIVE LE of directional atherectomy as a treatment modality that provides strong clinical outcomes in diabetics is a welcome and practice-changing finding.”
Garcia and Zeller, together with James McKinsey, chief of the Division of Vascular Surgery and Endovascular Interventions at New York-Presbyterian Hospital/Columbia University Medical Center, served as co-principal investigators for the DEFINITIVE LE study.
DEFINITIVE LE study design
The prospective, multicenter study comprised two cohorts—those with claudication and those with critical limb ischaemia. A total of 1,022 lesions (up to 20cm in length) were treated with the SilverHawk or TurboHawk plaque excision device. The study included a broad patient population, with 52% diabetic, 45% female and 75% claudicants, and a pre-specified sub-analysis comparing patency outcomes in diabetic and non-diabetic patients.
Several controls were included to ensure rigor in the study. These included Steering Committee oversight, adverse event adjudication by an independent physician Clinical Events Committee and endpoint analyses conducted by two different independent core laboratories—one that analysed acute angiographic results and another that analysed duplex ultrasound follow-up.