At VIVA 2016, the Vascular Interventional Advances Annual Conference, Michael R. Jaff, DO, from Harvard Medical School in Boston presented late-breaking 1-year results from the full clinical cohort of the IN.PACT Global Study, which aims to evaluate the safety and efficacy of the In.Pact Admiral drug-coated balloon (DCB; Medtronic) in real-world patients with challenging and complex lesions. IN.PACT Global is a large post-market surveillance study of drug-coated balloons for the peripheral arteries, enrolling more than 1,500 patients across 27 countries. The In.Pact Admiral device also received FDA approval in September for the treatment of in-stent restenosis (ISR) in the peripheral arteries, making it the first DCB to receive clearance for this indication in the United States.

Of the consecutively enrolled clinical cohort, 1,406 patients were treated with the In.Pact Admiral DCB and analyzed. The study included external monitoring and adjudication of all adverse events by an independent clinical events committee. Core-lab evaluations were performed on prespecified imaging subsets for subjects with long lesions (≥15 cm) (n=157), chronic total occlusions (CTO) (≥ 5 cm) (n=126) and in-stent restenosis (ISR) lesions (n=131). The primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CD-TLR). The 1-year data demonstrated a low CD-TLR rate of 7.5% in the entire study population with a mean lesion length of 12.09 cm; 18.0% in-stent restenosis lesions; and 35.5% occluded lesions. Additional safety and efficacy outcomes also included low rates of thrombosis (2.9%) and low occurrences of major target limb amputation (0.2%).

These results confirm safety and effectiveness of the In.Pact Admiral DCB in femoropopliteal lesions. The results continue to underscore the consistent safety and efficacy for the IN.PACT Admiral DCB. “Despite the complexity of these challenging lesions and patients, the outcomes were consistent across all patients, including the imaging subsets,” said Dr. Jaff. “Complex lesion types, including long lesions, chronic total occlusions and ISR remain challenging to treat with no clearly superior treatment options. These results demonstrate the effectiveness of the IN.PACT Admiral DCB as a primary therapy in treating these challenging patients who we routinely see in clinical practice.”

VDM: What would you say the significance is of the data and the low CD-TLR percentage rate? 

Jaff: The only data presented from IN.PACT Global prior to VIVA16 have been the predefined subgroup analyses that were the imaging cohorts, including data on in-stent restenosis, long lesions, and chronic total occlusions. So this is the first time that the entire cohort of patients has been presented. What was surprising to many after they saw the data is the fact that this is a much more complicated patient population than was studied in the randomized trial. To have such a low target lesion revascularization rate in a population of patients with much longer lesions and artery calcification  really raises a question about how well DCBs can perform. And I think it’s pretty impressive that they perform so well, particularly in a multicenter, multinational population of patients. 

VDM: How does this study differ from IN.PACT SFA?

Jaff: IN.PACT SFA was a prospective, multicenter, single-blinded, randomized trial in which 331 patients with intermittent claudication or ischemic rest pain due to superficial femoral and/or popliteal peripheral artery disease were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The lesion lengths were much shorter. The patient population was far less complex, with less artery calcification. So it’s an entirely different population. IN.PACT Global includes a population of patients who were chosen by investigators from all around the region that was studied in over 60 sites. So you have to presume that there were a lot of different skill levels of the operators and yet despite all of that, the results were really very good. There were no mandates to assess operator skill prior to enrollment. 

VDM: And rates of thrombosis and amputation were extremely low.

Jaff: Exactly. Who would have imagined that a DCB would perform this well when you have investigators from all levels of skill and all parts of the world with much longer lesions, much more anatomic complexities? 

VDM: What do you think a key takeaway message is for an interventionalist when they are considering these data?

Jaff: This fits beautifully into the debate that everyone’s having about the algorithm for the management of patients with peripheral artery disease. The number of choices of technologies is staggering now compared to even a mere 10 years ago. You’ve got uncoated balloons, bare nitinol stents, drug-eluting stents, fabric-covered stents, atherectomy devices, crossing devices, scoring devices, on and on. Then you add DCBs, which previously had great results compared to balloon angioplasty but only in very straightforward patient populations. Now we see similar degrees of efficacy with very low TLR rates from regions around the world with a DCB, and it makes you wonder, where do DCBs fit into the treatment algorithm? It has to be considered among a group of first-line treatments for patients with peripheral artery disease. I’m not saying it’s the only first-line treatment. I’m saying it has clearly emerged as one of the first-line therapies for patients with peripheral artery disease. 

VDM: So maybe you could answer a question for a lot of people if they were sort of on the fence about it but now they might not be.

Jaff: That, or they previously thought they could only use it in lesion lengths of 8 cm to 9 cm. Now we see efficacy in lesion lengths of a mean of 12 cm, the imaging cohorts extending all the way up to 26 cm with TLR rates that are comparable to what we saw in the randomized trials in other data sets. 

The other great thing about this study is that unlike most post-market surveillance registries, a clinical events committee was involved in adjudicating every adverse event here so this was not left up to the investigators to determine safety endpoints. These were determined by an independent clinical events committee, so it really lets you feel like there is validity to the summary of the results.

VDM: What other information do you think is still needed for this particular device?

Jaff: The one thing that is worth looking at, and that people have appropriately asked me a lot about, was the provisional stent rate of 25%. Despite successful use of the drug-coated balloon, they still had to place a stent 1 in 4 times. Why is that? We need to learn whether that was an operator experience issue, or if there was something that made stenting more necessary for the lesions that required a provisional stent compared to the lesions that didn’t. There are a lot of important questions about the patterns of failure of drug-coated balloons as well. In other words, when a patient has restenosis with a drug-coated balloon, is it a focal restenosis? Is it a long diffuse in-lesion restenosis? I think those are questions we need to answer.

VDM: For how long will this group be followed?

Jaff: The sponsor has agreed to follow these patients out for another 12 months beyond this.

VDM: Is there anything else that you think is important for endovascular clinicians to know?

Jaff: I think the only question that remains is, “Where does cost and cost effectiveness fit into the algorithm for treatment of PAD?” In my view, that has to be a part of any trial going forward. We need to understand in an affordable care model how we make decisions that show not only treatment efficacy but also cost effectiveness.

Editor’s note: Dr. Jaff reports unpaid consultancy to Medtronic.