Medtronic's In.Pact Admiral Drug-Coated Balloon Shows Superiority Versus Standard Angioplasty at 2 Years

October 14, 2015—Two-year results from the pivotal IN.PACT SFA trial were presented by John R. Laird, MD, at the 2015 Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco, showing sustained superior outcomes for the In.Pact drug-coated balloon (DCB, Medtronic, Inc.) over standard percutaneous transluminal angioplasty (PTA). The data were simultaneously published by Laird et al in the Journal of the American College of Cardiology (JACC). 

IN.PACT SFA is a prospective randomized trial evaluating the safety and efficacy of the In.Pact Admiral DCB versus standard PTA in the superficial femoral (SFA) and proximal popliteal arterial segments. In total, the trial enrolled 331 patients at 57 centers in the United States and Europe in a 2:1 fashion (DCB: 220 subjects, 221 lesions; PTA: 111 subjects, 113 lesions). IN.PACT SFA I enrolled 150 subjects at 13 European sites from September 2010 to April 2011, and IN.PACT SFA II enrolled 181 subjects at 44 US sites from April 2012 to January 2013. Inclusion criteria in the trial included Rutherford categories 2-4 and lesion lengths of 4 to 18 cm or occlusions ≤ 10 cm. The mean lesion length in the trial was 8.9 ± 4.96 cm. 

Key among the reported 2-year efficacy data were a primary patency rate of 78.9% in the DCB arm versus 50.1% in the PTA group (P < .001), with primary patency defined as freedom from core lab–assessed restenosis (duplex ultrasound–derived peak systolic velocity ratio [PSVR] ≤ 2.4) or clinically driven target lesion revascularization (TLR) through 24 months (adjudicated by a blinded clinical events committee). 

The reported rate of freedom from clinically driven TLR was 91% in the DCB arm versus 72.2% with PTA alone (P < .001). 

Safety outcomes included no major target limb amputations in either arm (P > .999); low rates of thrombosis (1.5% [3/198] for DCB vs 3.8% [4/106] for PTA; P = .243); but a higher rate of all-cause mortality in the DCB arm (8.1% [16/198] vs 0.9% [1/106]; P = .008). However, neither arm reported any occurrence of device- or procedure-related death (P > .999). 

In his presentation and in comments to Endovascular Today, Dr. Laird, an interventional cardiologist at UC Davis in California, summarized the 2-year findings from IN.PACT SFA as showing a sustained and durable effect of the In.Pact Admiral DCB, with significantly better primary patency compared to PTA alone, as well as a significant reduction in the need for TLR. He also noted that there was a similar improvement in clinical outcomes between the DCB and PTA arms (referring to 6-minute walking distance tests), but that the level of improvement was achieved with 58% fewer reinterventions in the DCB arm.

Putting the presented results from IN.PACT SFA into context, Dr. Laird noted that the 2-year data are a favorable continuation of the course from the trial’s 1-year data, which were published in Circulation and also showed significantly better primary patency and a very low TLR rate in the DCB arm. 

“We are seeing no late catch-up between the 1-year and 2-year time periods, with parallel Kaplan-Meier curves,” Dr. Laird told Endovascular Today. “The data are also consistent with previous experiences in the PACIFIER randomized trial and suggest that a relatively brief duration of paclitaxel delivery into the vessel wall can result in sustained clinical benefit.”

Commenting further on the significance of the 2-year mark in SFA trials, in particular those evaluating DCBs, Dr. Laird acknowledged that there have been questions as to whether DCBs will provide a durable treatment in both study and so-called “real world” populations and discussed the degree to which the current data address those concerns. 

“In this and the other [FDA investigational device exemption] trials, we’re treating relatively straightforward lesions,” he said, referring to those studies largely aimed at gaining regulatory approvals, which require a robust dataset derived from rigorous clinical evaluations with substantial oversight, but often do not include the complexity or severity of disease encountered in “real world” practice.

“The mean lesion length in IN.PACT SFA was close to 9 cm, which is longer than in some of the other stenting and DCB trials,” continued Dr. Laird. “But, we’re still talking about relatively short lesions. Still, it’s very reassuring to see that the results of IN.PACT SFA were sustained out to 24 months—that there was not a late drop in patency, and the antiproliferative effects of the paclitaxel were durable,” he said. 

Regarding the trend toward higher mortality in the DCB arm, Dr. Laird emphasized that the deaths were not determined to be related in any way to the procedures, while also putting the all-cause mortality rate of the PTA arm into historical context. “The all-cause mortality was higher in the patients treated with the DCB at a rate that was statistically significant, so that may raise concerns for some people. But the independent events committee looked at all of the deaths and found that they were not device- or procedure-related,” said Dr. Laird to Endovascular Today. “In fact, if you look at the mortality rate in the standard balloon angioplasty arm of the trial, it was remarkably low—much lower than would be expected in this type of trial. The mortality rate was 0.9% in the PTA arm of the trial, and if you look at similar trials over the past several years, the mortality rate is generally in the 3% to 11% range. Also, the mean time of death was around 560 days after the procedure, and that’s well after the paclitaxel has dissipated out of the artery. The preclinical work shows no trace of the paclitaxel at 320 days after the procedure. So, I think the excess mortality in the DCB arm occurred by chance, and the differences there may be driven by the remarkably low mortality rate in the standard balloon angioplasty arm.”

The IN.PACT SFA data presentation and publication also provided detailed subgroup analyses, in which the DCB was shown to provide clinical superiority and consistency across several patient types such as female sex and diabetics. Primary patency in women was 76.7% with In.Pact Admiral and 42.3% with PTA alone (P < .001), and 80.2% versus 53.7% in men (P < .001). The patency rates in diabetic patients were 73.3% and 45.8% in the DCB and PTA arms, respectively (P < .001), and 82.5% and 54.5% in nondiabetics (P < .001). 

Duplex ultrasound follow-up in IN.PACT SFA will take place again at 3 years, and clinical follow-up will continue out to 5 years. In its announcement of the data presented at TCT and published in JACC, Medtronic also stated that 2-year health economic data from the IN.PACT SFA US cohort and 1-year data from the IN.PACT Global Study in-stent restenosis cohort are expected to be presented at the Vascular Interventional Advances (VIVA) 2015 meeting in November.