Marlene Busko

May 15, 2017

NEW ORLEANS, LA — Among patients who had advanced peripheral arterial disease (PAD) and underwent revascularization of an artery in the back of the knee, those who also received an adventitial injection of an anti-inflammatory steroid had a smaller rise in inflammatory biomarkers that have been tied to restenosis[1].

Dr Ehrin J Armstrong

Dr Ehrin J Armstrong (Denver VA Medical Center and University of Colorado) presented these secondary outcomes from the Dexamethasone Infusion to the Adventitia to Enhance Clinical Efficacy after Femoropopliteal Revascularization (DANCE) study in a late-breaking clinical-trial session here at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions.

Patients in DANCE had severe PAD and underwent balloon angioplasty alone or with atherectomy to unblock the femoral and/or popliteal arteries, and they also received an injection of dexamethasone delivered from the site of the former blockage to the tissue outside the artery using the Bullfrog (Mercator MedSystems) device.

The primary efficacy and safety outcomes from DANCE were recently reported at the International Symposium on Endovascular Therapy (ISET) and Leipzig Interventional Course (LINC) meetings.

The current study showed that a day after the revascularization procedures, patients in DANCE had a blunted rise in C-reactive protein (CRP) and a drop in monocyte chemoattractant protein-1 (MCP-1)—two biomarkers that are associated with restenosis.

This might "potentially explain a mechanism underlying the excellent" 12-month patency results, said Armstrong. "It's a little counterintuitive, but many of the initial clinical signals that initiate the pattern of restenosis do come from the adventitia," he noted.

Session comoderator Dr Gregg W Stone (Columbia University Medical Center and the Cardiovascular Research Foundation, New York) observed that an adequately powered, randomized study is needed to confirm the findings. Moreover, "femoropopliteal segments are different from the coronary arteries," and so far, drug-coated balloons have not shown efficacy in below-the-knee revascularization.

Panel member Dr Deepak L Bhat (Brigham and Women's Hospital, Boston, MA) added that it is "fascinating" that "something done locally is affecting systemic inflammation—in a bad way in terms of the initial insult [from the revascularization], but then in a good way, presumably, with medication delivery."

Armstrong agreed that randomized trials and further study of potential mechanisms are needed. Randomized trials examining this add-on drug delivery in patients with PAD in the lower leg are just starting.  

This was "an intriguing study," session comoderator Dr Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York) commented to heartwire from Medscape, but "the limitation is that it's not a randomized study."

Patients with below-the-knee arterial blockage "are the critical-limb-ischemia patients who really have very little benefit from anything," she added. "This could be beneficial, so I'm looking forward to the future findings."

Drug-Delivery Device Safety, Efficacy

DANCE was a prospective, single-arm trial in 35 centers that investigated the use of the Bullfrog device in 159 patients who had atherectomy and 124 patients who had angioplasty to treat a blocked femoral and/or popliteal artery.

Most patients had Rutherford stage 3 significant, lifestyle-limiting claudication, Armstrong explained. The treated lesions were 75 mm to 89 mm long, and about 20% to 30% of the patients also had severe calcification.

The primary safety outcome showed that none of the patients had a major adverse limb event or died within 30 days of the procedure.

The primary efficacy outcome showed that at 12 months, 84% of the patients who had atherectomy and 79% of patients who had angioplasty had preserved patency, defined as freedom from restenosis and clinically driven target lesion revascularization (TLR).

Thus, adding dexamethasone was "associated with high patency and low clinically driven TLR rates with exceptional safety," Armstrong reported.

More DANCE Findings, New Trials Beginning

The current prespecified secondary analysis looked at the change in inflammatory biomarkers from baseline to 24 hours in a subset of patients in DANCE: 43 patients who underwent atherectomy and 52 patients who underwent angioplasty.

The change in biomarker levels were compared with control patients in DANCE Partner who did not receive adventitial dexamethasone: 18 patients who had atherectomy and 13 patients who had angioplasty to treat a blocked femoral and/or popliteal artery.

The rise in blood levels of CRP a day after the revascularization was smaller in patients who had also received steroids injected into the adjoining tissue.

Median Rise in CRP (%) at 24 Hours After Revascularization*

Revascularization type
DANCE, revascularization plus dexamethasone
DANCE Partner, revascularization without dexamethasone
P
Atherectomy 14 138 NS
Angioplasty 55 208 NS
*With vs without adventitial dexamethasone

Similarly, patients who had undergone revascularization with added steroid injections had a drop in MCP-1 blood levels a day later, whereas the other patients had an increase in this biomarker.

Mean Change in MCP-1 (%) at 24 Hours After Revascularization*

Revascularization type
DANCE, revascularization plus dexamethasone
DANCE Partner, revascularization without dexamethasone
P
Atherectomy -52 16 <0.001
Angioplasty -39 17 <0.003
*With vs without adventitial dexamethasone

Several new and ongoing trials are looking at this further.

LIMBO-PTA plans to enroll 120 patients in Europe with below-the-knee PAD, who will have percutaneous transluminal angioplasty and be randomized to usual care or adventitial dexamethasone.

Similarly, the Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization (LIMBO-ATX) trial is currently enrolling patients in the US with below-the-knee PAD, with a planned enrollment of 120. The patients will have balloon angioplasty and atherectomy and be randomized to usual care or adventitial dexamethasone

The Temsirolimus Adventitial Delivery to Improve Angiographic Outcomes Below the Knee (TANGO) phase 2 trial has just begun enrollment in the US, and TWIST is in the planning stages.

DANCE was funded by Mercator MedSystems . Armstrong discloses that he is a consultant for Abbott Vascular, Boston Scientific, and Spectranetics.

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