Medtronic, other devicemakers defend safety of paclitaxel devices

In the wake of a critical study, medical device companies presented fresh patient data Tuesday aimed at bolstering the safety profile of stents and medical balloons that contain a drug called paclitaxel to treat peripheral artery disease above the knee in the legs.

Some drug-eluting stents and drug-coated balloons use paclitaxel to prevent blood vessels from reclosing after they're opened up in medical procedures. But a critical meta-analysis in the Journal of the American Heart Association in December documented a surprising increase in death rates five years after the devices were used by pooling the results of 28 past randomized controlled trials.

At the LINC 2019 conference in Leipzig, Germany, on Tuesday, Medtronic presented new patient-level data that showed age, kidney problems, limb amputation and overall complexity of disease were strongly associated with mortality five years after Medtronic's In.Pact Admiral drug-coated balloon was used in 1,837 patients. Whether the patient got a high or lose dose of paclitaxel was not predictive of mortality in the Medtronic data.

"Results from this independent patient-level meta-analysis demonstrate no correlation between exposure to paclitaxel and mortality through 5 years," said the slides from the presentation Tuesday by Hawaii vascular surgeon Dr. Peter Schneider, who consults for Medtronic and its competitors. "Alternative hypothesis: Preliminary findings suggest follow-up visit compliance ... is associated with lower mortality risk. This needs further evaluation."

The devices in question are used to treat peripheral artery disease (PAD), a blockage in blood vessels in the lower legs that affects more than 7 million Americans and can lead to limb amputation in severe cases. The prevalence of PAD increases with age, and is more common among black patients, though it affects all groups of people.

Many different treatments for PAD are available. A growing number of patients are having skinny balloons temporarily inflated inside blocked vessels to open them up, and sometimes the physician leaves behind a metal mesh tube called a stent to keep the vessel open. In some cases, these devices are coated with paclitaxel to reduce the chances of vessel re-closure.

Paclitaxel devices like Medtronic's In.Pact Admiral and Boston Scientific's Eluvia drug-eluting stent are important to investors because of their strong commercial potential — analysts with Barclays Capital estimate the In.Pact Admiral alone accounts for more than $200 million in sales at a higher-than-average profit margin compared to the rest of the Medtronic portfolio.

The study analyzed past randomized controlled clinical trials using several kinds of devices, and found that patients who were treated with paclitaxel balloons and/or stents had a 68 percent greater relative risk of dying two years later, and a 93 percent higher relative risk of death five years after the procedure. (The findings do not apply to paclitaxel stents and balloons used in coronary arteries.)

Authors of the meta-analysis report called their finding "alarming" and postulated that "paclitaxel toxicity" related to the way the drug is formulated and applied to the devices could be causing the problem. But they offered no clear explanation. The Food and Drug Administration has opened an investigation into the matter.

Device makers have noted that the JAHA analysis included anyone who died in the trials for any reason, and did not take into account patient-specific factors that could have pointed to other factors that could be strongly associated with death, such as the patient's age and health history — data that were not available to the team that did the JAHA meta-analysis.

A consultant for Cook Medical, the Indiana-based maker of the popular Zilver PTX drug-eluting peripheral stent, emphasized at the LINC conference that the JAHA paper lacked any patient-level data. "Cook's patient-level data demonstrate no increased mortality rates at five years with use of a Zilver PTX paclitaxel-coated stent vs. the use of non-coated stents and balloons," said Dr. Michael Dake, global principal investigator for the Zilver PTX randomized controlled clinical trial.

Boston Scientific consultant Dr. William Gray, meanwhile, said the company's Eluvia drug-eluting stent and Ranger drug-coated balloon did not have higher mortality rates at three years than non-paclitaxel devices, according to patient-level data presented at LINC.