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Adventitial drug delivery yields benefit in PAD
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NEW ORLEANS — Localized delivery of dexamethasone into the adventitia of the superficial femoral artery or popliteal artery via a novel micro-infusion device resulted in significant reductions in inflammatory biomarkers, which may provide a new strategy for outcome prediction and personalized therapy for patients with peripheral artery disease.
“Adventitial infusion and targeting of inflammation represents an appropriate and compelling change to established treatments among patients with advanced PAD. This potentially holds significant future prospects for the treatment of PAD,” Ehrin J. Armstrong, MD, MSc, FSCAI, director of the VA Eastern Colorado Healthcare System and associate professor of medicine at University of Colorado School of Medicine, said during a late-breaking clinical trial session at the Society for Cardiovascular Angiography and Interventions Annual Meeting.
The DANCE trial evaluated dexamethasone infusion (1.6 mg per cm of treated artery) to the adventitia via the Bullfrog Micro-Infusion Device (Mercator MedSystems) to enhance clinical efficacy after femoropopliteal revascularization. The overall goal of the trial was to overcome limitations of percutaneous transluminal angioplasty (PTA) and atherectomy, the current treatment options for PAD.
The trial population of 281 patients had a mean age of 68 years, was primarily male and two-thirds had Rutherford 3 claudication . Lesion length was consistent or slightly longer than those typically enrolled in femoropopliteal studies, with mean lesion lengths of 75 mm to 89 mm. Nearly one-third had severe calcification.
Previously presented topline results showed primary patency of 84% among patients who received atherectomy and PTA along with dexamethasone and 79% among those who received PTA only along with dexamethaso ne , high freedom from target lesion revascularization, no major adverse limb events and overall safety, Armstrong said .
At SCAI 2017, Armstrong presented results of a subgroup analysis of inflammatory biomarkers in 52 patients who underwent PTA and 42 who underwent atherectomy before and after using the Bullfrog Micro-Infusion device . A control group comprising 1 3 patients who underwent PTA and 1 8 who underwent atherectomy, who did not receive dexamethasone following the same techniques, was used as a comparison. Both groups had blood drawn prior to intervention, at 24 hours and at 4 weeks after the procedure.
The treatment group had a significant reduction of high-sensitivity C-reactive protein and monocyte chemoattractive protein-1 (MCP-1).
In the control group, the average 24-hour increase in high-sensitivity CRP was 208% among those who underwent PTA and 138% among those who underwent atherectomy, compared with a 55% increase among those who underwent PTA and received dexamethasone and 14% among those who underwent atherectomy and received dexamethasone. This finding was nonsignificant, according to Armstrong.
When the researchers analyzed MCP-1, the control group had an average 24-hour increase of 17% among those who underwent PTA and 16% among those who underwent atherectomy. In the treated group, the mean reduction in MCP-1 was 39% in the PTA group (P < .003) and 52% in the atherectomy group (P < .00005).
These findings “confirm that the addition of adventitial dexamethasone is associated with a significant reduction in measures of these inflammatory biomarkers that are known to be associated with restenosis," Armstrong said during his presentation.
During a discussion of the trial, Gregg W. Stone, MD, professor of medicine at Columbia University, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center, director of medical research and education at the Cardiovascular Research Foundation and a member of the Cardiology Today’s Intervention Editorial Board, said “the elephant in the room is when there would be an adequately powered randomized trial to really provide this is true.”
“I think that’s what the PAD field really needs,” Deepak L. Bhatt, MD, MPH, FSCAI, executive director of interventional cardiovascular programs at Brigham and Women’s Heart and Vascular Center, professor of medicine at Harvard Medical School and Cardiology Today’s Intervention Chief Medical Editor, said during the panel discussion. “As we’ve done in coronary intervention, do adequately sized randomized trials that have been lacking in the peripheral field for many years now.”
Armstrong concluded that there are several trials of adventitial drug delivery underway or in planning stages, including: LIMBO-PA, LIMBO-ATX, PRT-201-115, TANGO and TWIST. The LIMBO trial, currently enrolling, is of a randomized design, he said. – by Katie Kalvaitis
Reference:
Armstrong EJ , et al . Late-Breaking Clinical Trials I. Presented at: Society for Cardiovascular Angiography and Interventions Annual Meeting; May 10-13, 2017; New Orleans.
Disclosure: Armstrong reports no relevant financial disclosures.