FDA evaluating stents, balloons with paclitaxel coating following JAHA evaluation

A December study in The Journal of the American Heart Association by Konstantinos Katsanos, MD, of Rion, Greece, et al, reported a higher risk of death after balloons and stents used to open vessels in the legs were coated with an anti-inflammatory chemo agent called paclitaxel.
“Further investigations are urgently warranted,” Dr. Katsanos concluded after synthesizing the results of 28 randomized controlled trials of stents and drug-coated balloons used above the knee in the legs.

The FDA is “evaluating” the new information presented by the study and recommended that healthcare providers continue closely watching patients who have been treated with the drug-eluting devices. However, currently the FDA believes that the benefits continue to outweigh the risks for approved paclitaxel-coated balloons and paclitaxel-eluting stents when used in accordance with their indications for use.
The FDA also plans to assess long-term follow-up data from studies that supported the approval of paclitaxel-coated balloons or paclitaxel-eluting stents in the U.S. Specifically, the regulatory group is slated to focus on causes of death within these studies, paclitaxel dose delivered and patient characteristics.
A Medtronic statement to Vein Therapy News following publication of the article noted that after reviewing the findings carefully, Medtronic’s conclusion that there is a connection in mortality and paclitaxel drug-based toxicity as the authors stated was made without having patient-level data so they would have been unable to establish a plausible mechanism of action between drug-based toxicity and death.
“At Medtronic, patient safety is a top priority and we recognize Katsanos et al for this work to address the important question on an increased mortality rate in paclitaxel-coated balloons and paclitaxel-eluting stents studies,” Medtronic stated. “We have reviewed these findings carefully and caution the conclusion that there is a connection in mortality and paclitaxel drug-based toxicity as the authors did not have access to patient level data and were unable to establish a plausible mechanism of action between drug-based toxicity and death.”
The stents studied in the data review, called a meta-analysis, include Medtronic’s In.Pact Admiral drug-coated medical balloon and Boston Scientific’s Ranger drug-coated balloon and Eluvia drug-eluting stent.
Representatives of both Medtronic and Boston Scientific told investors at the J.P. Morgan Healthcare Conference in San Francisco in early January that they could not find any support for the higher death rates documented in the JAHA article.
Medtronic Cardiac and Vascular Group President Mike Coyle told investors that the company had generated a ton of clinical evidence: 1,800 patients, data out to five years, a randomized controlled study for the United States, a randomized controlled clinical study for Japan, and global registry data. “And all of these data have been analyzed, and we have not seen this safety signal in our data.”
As reported in the December/January issue of Vein Therapy News, IN.PACT Admiral is the only commercialized drug coated balloon that has data presented out to five years. Medtronic has made numerous updates in reporting the safety and efficacy in the trial data over the past five years.
“This meta-analysis includes our previously published findings on the all-cause mortality rate across our trials, which have gone through independent clinical events committee analyses that determined that no deaths were related to IN.PACT DCB or paclitaxel,” the statement continued. “Additionally, a review of published literature has deemed that the mortality rates across our IN.PACT DCB studies are within the range with other non-drug eluting technologies.
“We remain confident in the performance and long-term safety of IN.PACT DCB and believe strongly that additional, patient-level analyses are needed to validate this conclusion. We are dedicated to working closely with our primary investigators of the IN.PACT studies and independent researchers to help further answer the question around this mortality trend and explore other factors that could play a role. In line with our commitment to data transparency and to our physicians and the patients we serve, it is important that we continue to review, report, and publish our findings on this topic.”
Boston Scientific Global Chief Medical Officer Ian Meredith told the Minneapolis Star-Tribune that meta-analyses like the paclitaxel-device study in JAHA sometimes reach findings that are not borne out in later studies.
Meredith also told the newspaper that the broad, study population-level data offered no explanation for the potential mechanism behind the deaths.
“I think at this stage, good clinical studies are appropriate,” Meredith was quoted as saying. “There does not seem to be a plausible mechanism to understand how a dose that is imperceptible in plasma or tissue at 30 days could actually really affect mortality two years and beyond.”
Dr. Katsanos, responding to the newspaper by email, said he understood the skepticism of the industry, “but at the end of the day, the statistical signal is too strong to be ignored by reasonable doubt.” VTN

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Camden Lawless

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