A long-term real-world experience with Stellarex (Philips) drug-coated balloons (DCB) in the periphery strengthens the mass of recent evidence largely acquitting it and other paclitaxel-coated devices of any special mortality hazard.
A 4-year analysis based on the ILLUMENATE Global postmarket registry suggested that the DCB was safe and effective in a broad population of patients with often complex femoropopliteal lesions, fewer than one-third of whom required stents on a provisional basis.
Their target-limb amputation rate was only 0.8% and all-cause mortality was 8.1%, “very low for a cardiovascular patient group with claudication,” said Andrew Holden, MB, ChB, Auckland City Hospital, New Zealand, reporting the results during TCT Connect, the virtual edition of Transcatheter Cardiovascular Therapeutics (TCT) 2020.
The findings were consistent across prospectively defined subgroups by sex, diabetes, and target-lesion length, as well as the broader ILLUMENATE trial experience encompassing more than 2000 patients, he said.
And they impressed observers at TCT Connect, who called for an end to any stigma against paclitaxel-coated devices in peripheral vascular disease (PAD) and for tighter focus on randomized trials to refine their selection and targeted use.
As chronicled at length by theheart.org | Medscape Cardiology, a controversial meta-analysis published in December 2018 upended clinical trials looking at paclitaxel-coated devices for PAD revascularization by tying them to an almost 70% jump in relative risk (RR) for mortality at 2 years and a 93% RR increase at 5 years.
The findings led to a warning letter regarding the alleged risk from the US Food and Drug Administration (FDA), followed by a comprehensive public analysis by the agency and its independent advisors in June 2019, which acknowledged the existence of a safety signal.
Four months later, the FDA approved two sizes of the Stellarex for de novo and restenotic lesions in the superficial femoral and popliteal arteries. They joined other Stellarex DCBs and paclitaxel-coated peripheral devices already on the market, all of which account for the safety signal in their labeling.
“The mortality at 4 years is strikingly low. Normally, in a population like this, we would expect it to be at least 10% to 20% at 4 years,” Peter A. Schneider, MD, University of California, San Francisco, said as an observer of ILLUMENATE-Global at a media briefing.
“So, far from a doubling of mortality risk with paclitaxel, actually this appears to be less than what we would expect for a population like this.”
At the same press conference, Robert Lookstein, MD, MHCDL, said the findings represent “just really spectacular data in a real world subset — high degrees of severe calcification, high preponderance of diabetics. I think this just further reinforces the broad consensus among vascular specialists that DCB has really become the go-to therapy for patients with lifestyle-limiting claudication.”
ILLUMENATE-Global “is just another valuable contribution to the literature suggesting that this Stellarex balloon is a safe and effective technology in a real-world population,” said Lookstein, Ichan School of Medicine at Mount Sinai, New York City.
“I think right now, many of us are looking to put the paclitaxel issue behind us as we’re trying to make a decision on which device to use for which patient,” he said after Holden’s presentation of the study elsewhere at TCT Connect.
The world of paclitaxel DCBs for the periphery also include the IN.PACT Admiral (Medtronic) and Lutonix (Bard), which — although tempting to lump together — differ in key ways that could affect their safety, effectiveness at PAD revascularization, and restenosis risk. They include the paclitaxel dosage as well as delivery and absorption characteristics of the balloon coating that conveys the drug.
Clinical trial or registry results for one of the DCBs don’t necessarily apply to the other devices, Schneider emphasized at the briefing. “Each device has to stand on its own, and this is where having this kind of follow up — a lot of patients, 4 years, with specific end points — is important for us to understand what we’re dealing with.”
The current analysis involved 371 patients at 37 sites in Europe, Australia, and New Zealand who received Stellarex for a total of 417 fem-pop lesions that ranged widely in complexity and length, ranging up to 20 cm (mean, 7.5 cm).
The predominantly male patients averaged about 68 years in age, 34% had diabetes, and the mean ankle-brachial index was 0.70. Interpretation of angiograms, duplex ultrasounds, and clinical event was conducted at central core laboratories.
Of the treated lesions, 75% were in the mid- to distal superficial femoral artery (SFA), 11% were in the proximal SFA, and 9% and 5% were in the proximal and mid-to-distal popliteal artery, respectively; 94% were de novo and 41 were severely calcified, Holden reported.
Of the entire cohort, 77.9% met the primary safety end point of freedom from device- and procedure-related death at 30 days and from target-limb major amputation or clinically driven target-lesion revascularization (TLR) through 12 months.
Only three patients required target-limb amputation throughout the follow-up. All-cause mortality was 0.5% at 1 year and 2.4%, 5.1%, and 8.1% at 2, 3, and 4 years, respectively. Freedom from clinically driven TLR was 75.5% at 4 years.
“These observational studies are useful in terms of understanding the patterns of utilization, and then also to look at overall aggregate event rates. Here I think you were quite low for amputation and mortality, which is reassuring,” said Marc P. Bonaca, MD, MPH, University of Colorado School of Medicine, Aurora, after Holden’s presentation of the analysis.
Regarding the abundant choices of paclitaxel-delivering devices for the periphery, he said, “we need to look to head-to-head trials in randomized fashion, and decide what end points, in which populations, what matters here, and how we measure that in order to help us guide our clinical use.”
At the same forum, Lookstein said, “I would call on all of us, as vascular specialists and trialists, to develop the next set of comparative effectiveness research to try and answer these questions.” Such research so far “has been anemic at best, with only fewer than a handful of trials comparing one device to another,” he said.
“We’re sort of closing the door on paclitaxel as a safety issue. We really need to start comparing device to device, and look for truly which patient demographics are best suited for which specific balloon, which specific stent, which specific technology.”
TCT Connect is sponsored and run by the Cardiology Research Foundation, which, it frequently notes on the meeting site, “gratefully acknowledges the educational grant support from the ‘Major Benefactors’ Abbott, Boston Scientific, Edwards, and Medtronic,” among other companies. ILLUMENATE Global was funded by Philips Image Guided Therapy. Holden is an investigator in the ILLUMENATE trials and a member of the medical advisory board for Philips. Schneider discloses receiving honoraria or consulting fees or serving on a speakers bureau for Medtronic, Boston Scientific, Cordis, Intact Vascular, Surmodics, and Silk Road Medical. Lookstein discloses receiving honoraria or consulting fees or serving on a speakers bureau for Boston Scientific, Medtronic, Penumbra, and Abbott Vascular; and holding stock options or equity interest in Truvic. Bonaca discloses receiving grant support or a research contract from AstraZenca, Bayer, Medtronic, Merck/Schering Plough, Sanofi-Aventis, Amgen, and Janssen.
Transcatheter Cardiovascular Therapeutics (TCT) 2020. Endovascular 1: Late-Breaking Clinical Trials and Science. Presented October 18, 2020.