CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.
“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”
Dr. Patrick Geraghty
Dr. Geraghty focused on several future directions for PAD treatment: improved drug-eluting stents (DES) for superficial femoral artery disease; drug-coated balloons and modified DES for infrapopliteal disease; biologic modifiers for claudication and CLI; and bioresorbable, drug-eluting scaffolds for infrainguinal interventions.
“You’re not simply a plumber anymore; you’re a biological response modifier,” Dr. Geraghty said, explaining that biologic response modification technologies are the logical successor where standard surgical and endovascular techniques have either fallen short (as in early patency loss due to restenosis) or failed to offer effective alternatives (as in no-option advanced CLI patients). “And that takes many of us out of our comfort zone,” he said.
Dr. Geraghty noted the VIBRANT trial (J Vasc Surg. 2013;58[2]:386-95) and similar studies of non–drug eluting constructs identified early restenosis as the primary culprit in endovascular patency loss. “If you could reduce those early patency losses, you’d have an admirable primary patency rate for these complex lesions,” he said. “We’re able to reconstruct a vessel lumen. The question is, how to best maintain it?”
To answer that, Dr. Geraghty noted that the SIROCCO II trial (J Vasc Interv Radiol. 2005;16[3]:331-8) failed to show an advantage for a sirolimus-eluting stent over bare nitinol stent for superficial femoral artery (SFA) disease, but the subsequent Zilver PTX trial showed the benefits of paclitaxel-eluting stents over 5 years (Circulation. 2016;133[15]:1472-83).
He noted that drug-coated balloons (DCBs) trials have yielded mixed results in infrapopliteal intervention. Most notably, the multicenter In.Pact DEEP trial (Circulation. 2015;131[5]:495-502) failed to show treatment efficacy, Dr. Geraghty said. “The In.Pact DEEP results sharply contrasted with the positive data from trials of similar DCBs in the SFA” (N Engl J Med. 2015;373[2]:145-53).
With regard to DES for infrapopliteal disease, Dr. Geraghty noted the promise of positive results of the ACHILLES (J Am Coll Cardiol. 2012;60[22]:2290-5) and DESTINY (J Vasc Surg. 2012;55[2]:390-9) trials, along with the modest structural changes needed to convert from coronary to proximal tibial applications.
Bioresorbable vascular scaffolds (BVS) for CLI have also made recent advances. “It has been a slow road, but I’m happy that industry has pursued this aggressively,” Dr. Geraghty said. He pointed out that the ESPRIT I trial of bioresorbable everolimus-eluting vascular scaffolds in PAD involving the external iliac artery and SFA reported restenosis rates of 12.1% and 16.1% at 1 and 2 years, respectively (JACC Cardiovasc Interv. 2016;9[11]:1178-87). A trial of the Absorb BVS (Abbott) for short infrapopliteal lesions showed primary patency rates of 96% and 85% at 1 and 2 years, he said (JACC Cardiovasc Interv. 2016;9[7]:715-24).
“Vascular surgeons should be tracking BVS technology closely,” Dr. Geraghty said. “It achieves multiple desirable goals: immediate scaffolding for luminal restoration; mitigation of the restenotic stimulus via stent resorption; drug delivery for inhibition of restenosis; and the prospect of simpler re-interventions.”
Stem/progenitor cell therapies may also provide new solutions for no-option vasculature. One trial that showed “promising trends,” Dr. Geraghty said, is the RESTORE-CLI study of bone marrow aspiration (Mol Ther. 2012;20[6]:1280-6). “This trial reported a trend toward improved time to failure and reduced amputation-free survival, but did not meet its primary endpoint,” he said. “Likewise, the recently presented Biomet MOBILE data failed to meet its primary endpoint, but showed favorable trends in some treatment subgroups” (J Vasc Surg. 2011;54[6]:1650-8).
Dr. Geraghty noted that trial design in this field may need to change directions. “Look at the Delphi consensus matrices for the WIfI (Wound, Ischemia, foot Infection) Threatened limb Classification System (J Vasc Surg. 2014;59[1]:220-34). These show that complex wounds bear a significant risk of amputation, perhaps unmitigated by successful revascularization.” In addition, he called amputation-free survival “a rather blunt instrument” for evaluating how therapies impact limb outcomes and said it can confound the analysis of their effectiveness.
“Instead of confining the progenitor-cell therapies to no-option CLI trials, I’m eager to also see them investigated for treatment of claudication,” Dr. Geraghty said. “Can cell-based therapies possibly displace endovascular interventions as the first-line, least-harmful option for claudication?”
Dr. Geraghty also touched on intra/extravascular adjuvant therapies: antithrombin nanoparticles; inhibitory nanoparticles and polymeric wraps; and adventitial drug delivery techniques, among others.
“It’s critically important for vascular surgeons to position themselves for continued success in CLI treatment,” he said. “That involves aggressive practice branding, active trial participation, critical analysis of new technologies, and adoption of new, even disruptive, treatment modalities that show patient benefit.”
Dr. Geraghty disclosed stock ownership in Pulse Therapeutics; consultant fees from Bard Peripheral Vascular, Boston Scientific, Intact Vascular, Bard/Lutonix and Spectranetics; and serving as principal investigator for trials by Cook Medical, Bard/Lutonix, and Intact Vascular, with fees going to Washington University Medical School.