IN.PACT AV three-year subanalysis trial data show “durable” long-term results

Yesterday’s Vascular Access Masterclass session saw a Podium First presentation by Andrew Holden (Auckland, New Zealand) in which he presented new data from the IN.PACT AV Access trial of the IN.PACT AV (Medtronic) drug-coated balloon (DCB). Offering three-year subanalysis data, he said that the study is “the only randomised pivotal trial of a device treating dysfunctional arteriovenous fistulas (AVFs) to demonstrate consistent and sustained clinical benefit” up to three years.

ESTABLISHING SOME background to the study, Holden noted that there have been eight published peer-reviewed studies with outcomes reported through to three years, but he said that all of these were singlecentre with no adjudication—and that “all except one were single-arm and retrospective”. That means there is, in his words, “a paucity of evidence of long-term outcomes after treatment of stenoses in AV access”.

The IN.PACT AV study was initially planned to extend to 24 months, and a five-year extension meant a shrinking of the pool of participants as a result of death, withdrawal and declined consent to further study. In total, 133 participants completed their threeyear visit out of an original cohort of 330 patients receiving the index procedure. Of that 330, 170 were in the IN.PACT AV arm, while 160 received percutaneous transluminal angioplasty (PTA). In the IN.PACT AV arm, the mean age was 65.8 years and 112 of 170 were male. The standard PTA arm had a mean age of 65.5 and 101/160 were male.

As presented last year at CX, at 36 months, the DCB arm yielded a target lesion primary patency (TLPP) rate of 43.1% while the PTA arm had a rate of 28.6%, a statistically significant patency advantage for the DCB. This year, Holden set out for the first time the results of subgroup analyses in patients receiving an AVF in the forearm and upper arm at three years.

Those analyses included one in which the results were stratified by AVF type. In that analysis, the

Moving on to outline the latest data with Axess from an EU first-in-human (FIH) study, Moll detailed that enrolment of a total of 20 patients across six sites has now been completed. As per follow-up data, which were available for all 20 patients, primary patency rates of 80% at six months and secondary patency rates of 100% at 12 months were achieved. The speaker also reported that no infections were observed. A full follow-up period of five years is now planned in these patients, and is ongoing.

Moll also provided attendees with insight based on surgeon feedback from the first 20 Axess implants—alluding to the fact it is a similar procedure to standard AVG implantation; the device being easier to suture and softer than traditional expanded polytetrafluoroethylene (ePTFE) products; and its improved adaptation to patient arteriotomy/ venotomy proving “very helpful” in fragile vessels. A prospective, single-arm EU pivotal trial of Axess is now also actively enrolling patients, at up to 25 sites spanning nine countries and with a total followup period of five years. Moll noted that enrolment in this larger-scale study began in Q4 2022. Among the key study endpoints is freedom from devicerelated serious adverse events during the first six months after implantation, and the pivotal trial is also powered to assess both primary and secondary patency rates.

IN.PACT AV arm had a patency rate of 44.5% in forearm (radiocephalic) AVFs and 39.9% in upper arm (brachiocephalic and brachiobasilic) AVFs at 36 months, while the same rates with PTA were 33.8% and 21.3%, respectively. The patency advantage for DCB was significant for both forearm and upper arm fistulas. The authors also stratified results by lesion type, with a DCB rate of TLPP of 50.6% at 36 months for de novo lesions and 40.5% for restenotic lesions. This was statistically superior to TLPP rates for PTA which were 42.2% and 22.7%.

Lesion location

A further subgroup analysis by lesion location focused on peri-anastomotic, cephalic arch and venous outflow lesions. For peri-anastamotic lesions, IN.PACT AV had a TLPP rate of 40.4% while PTA had a rate of 31.1% at 36 months. For cephalic arch lesions, the DCB arm saw a rate of 40.9% and the PTA arm one of 27.9%, while on venous outflow lesions the former had a rate of 45.6% and the latter of 25.5%. While patency was statistically superior at all lesion locations, the most notable effect was seen in perianastomotic and cephalic arch lesions.

For the first time, the 48-month all-cause mortality results were presented which again showed no evidence of a safety concern using a paclitaxel-eluting device in the AV access circuit. The mortality at 48 months was actually higher in the PTA arm at 41.8% compared to to the DCB arm where mortality was 34.6% although this did not reach statistical significance.

Summarising the findings, Holden stated that they demonstrated “sustained patency benefit for IN.PACT AV DCB compared to PTA in all subgroup analyses”, and he highlighted restenoses, perianastomotic and cephalic arch lesions in particular. Concluding his talk, he said: “Durable long-term data suggest the use of IN.PACT AV DCB as a standard of care for AVF maintenance in patients with end-stage kidney disease.”