Nearly 1 Year Later, Endovascular Community Continues to Struggle With Paclitaxel

LAS VEGAS, NV—After nearly a year of analyzing and reanalyzing data to try to understand the vexing signal of long-term mortality with paclitaxel-based devices in patients with femoropopliteal artery disease, new ideas are emerging as to how individual health systems can navigate restrictions on their use.

Since the publication in December 2018 of a meta-analysis that sent the endovascular community reeling, every major vascular and cardiovascular meeting held this year has devoted at least one session—some lasting a full day—to in-depth discussions of paclitaxel. Large real-world Medicare analyses, led by Eric Secemsky, MD (Beth Israel Deaconess Medical Center, Boston, MA), have found no support for the mortality signal, and neither has the recent BARMER health insurance study from Germany.

Amidst the academic headaches of missing data and debates on how best to analyze and pool the underpowered randomized trial and registry numbers that are available, clinical confusion has been a recurrent theme: given all the uncertainty, how best can physicians treat their patients today?

“There’s a mixture in the community. There are those who, with the greater and larger real-world population findings, are now much more comfortable and are slowly going back to using paclitaxel-based devices. Then there are those who are still not using them because of fear of lawsuit,” said Gary Ansel, MD ( OhioHealth Riverside Methodist Hospital, Columbus), in an interview with TCTMD following a special paclitaxel session here at VIVA 2019.

From Moratorium to Resolution

In the presentation he gave at VIVA, Ansel described the steps that his large healthcare system in Ohio used to navigate the controversy and to reach a solution quickly. Following the first letter from the US Food and Drug Administration last spring recommending that alternative therapies to paclitaxel be used for most patients, Ansel said his institution put an “absolute moratorium” on the devices. Within 24 hours they had been removed from shelves or taped off and there was “zero percent usage,” which he said did not always go over well with some clinicians who wanted to use them in their high-risk patients. During this time, Ansel said, monthly discussions were held and any new peer-reviewed data were presented. He described how several dozen patients eligible for paclitaxel-based therapy were told their procedures had to be put on hold.

But in the weeks following the FDA advisory committee meeting, held in June, Ansel’s institution lifted their moratorium after discussing what had been presented there, including the advisory committee’s recommendation that the devices should remain on the market and that, at least in the short term, their benefit appeared to outweigh the risk.

To TCTMD, Ansel said other large healthcare systems have expressed interest in their experience and in using this type of multidisciplinary team approach of clinicians, administrators, and legal representatives to achieve fast resolution on this issue.

“I can tell you we went over the published literature in detail,” Ansel said. “It was interesting how easily people voiced their concern early on, and [then] got away from those concerns as the data became more and more apparent. It was refreshing for all of us to see the politics leave and just focus on the patients.”

Clearing the Smoke

The other key piece of this was decided on wording that should be added to consent forms when patients are being offered paclitaxel-based therapy. Ansel’s institution decided on: “The procedure alternatives and risk/benefit of drug devices has been discussed and their use is acceptable.”

While these discussions with patients can sometimes be difficult, “what we’ve tried to do is balance the meta-analysis and the patient-level data with the [Medicare data] where there’s no signal,” he said. “I think for patients that’s very reassuring, because the vast majority are Medicare patients.” A significant portion of the time at the FDA advisory panel meeting in fact was devoted to the problem of how to convey all of the known and unknown information to patients, most of whom likely have never even heard of a meta-analysis.

“There have been a couple of patients [in our experience] who have said, ‘If there’s any risk, I don’t want to take it,’” Ansel noted. “But the vast majority of them say ‘I’m willing to take the risk because of the benefit.’ It’s really a shared-decision process at that point in time.”

The ability of all stakeholders in the healthcare decision-making process to agree to remove procedure restrictions from patients who are waiting, based on emerging data such as the Medicare analyses, signals an important change in the arc of the paclitaxel story, Ansel agreed.

Krishna J. Rocha-Singh, MD (Prairie Heart Institute, Springfield, IL), who began this week’s paclitaxel session by saying “it is time to turn the page” and to use real-world datasets to inform discussions and decisions, noted that VIVA has conducted additional soon-to-be-published analyses of its own that include examination of outcomes according to the amount of drug on the balloon when patients were treated. His presentation showed no consistent effect across increasing doses, with patients in the medium dose range at lower risk than those at low or high doses.

Rocha-Singh concluded that emerging real-world analyses, particularly the ones from the Medicare population, are helping to clear “some but not all the smoke in the room” with regard to the ongoing paclitaxel controversy.