Abbott Northwestern Hospital, a major center for vascular medicine in the Twin Cities, has stopped using medical devices in the legs that contain paclitaxel amid a growing international debate over the devices' long-term safety.

"Right now, since we don't have an answer, I think you have to proceed with caution," Abbott Northwestern vascular surgeon Dr. Jason Alexander said. "Until we have that answer, at Abbott, we are proceeding with extreme caution and we are just not using those particular devices."

Health care providers are taking different approaches to a sweeping analysis of past studies published last month in the Journal of the American Heart Association (JAHA). The study reported that patients who had paclitaxel-coated stents and balloons used to open blocked blood vessels above the knee had a higher rate of death two years later, and even higher mortality at five years. Regulators are investigating, competing papers are being prepared for publication, and a major medical meeting in Germany on Tuesday will debate the issue.

At Mayo Clinic hospitals, doctors who use paclitaxel-coated stents and medical balloons to reopen blocked blood vessels in the legs are making decisions based on each individual case, after considering other factors like how urgently the device is needed and the underlying health conditions of the patient.

"I think you just have to keep going the way you are going, but also fully disclose to the patient that there is a paper that says this," Dr. Sanjay Misra, chairman of the research committee at the Mayo Clinic Gonda Vascular Center in Rochester, said Monday. "If the patient says 'no,' then I think the patient has decided. But I think the thing I would add is to explain that this is one paper that looked at all the trials that were available at that moment in time."

Misra said Mayo Clinic staff are in the process of bringing together stakeholders involved in the care of patients with peripheral artery disease to discuss what to do in the use of these devices.

Doctors have long used small balloons and metal-mesh tubes to reopen clogged blood vessels in the heart. More recently, those same types of devices have been used in the legs.

Paclitaxel is applied to many of them by the manufacturers because the drug has been shown to lower the risk of the target vessel reclosing after the procedure. (The increased risk of death has not been shown to be associated with paclitaxel devices used in coronary arteries.)

At Abbott Northwestern in Minneapolis, vascular physicians in late December collectively decided that the mortality risks documented in the JAHA paper were too high, and too unexplained, to continue using paclitaxel devices in the lower extremities until better information is available.

For the time being, procedures with stents and balloons above the knee in the legs at Abbott Northwestern will be done with devices that are not coated in the drug — a decision that will affect about 15 to 20 people per month who get medical interventions for peripheral artery disease, Alexander said.

In an interview, Alexander said the decision to temporarily stop using devices like Medtronic's In.Pact Admiral drug-coated balloon and Boston Scientific's Eluvia peripheral drug-eluting stent came after a close reading by multiple doctors of the peer-reviewed JAHA paper.

"We initially thought, this doesn't make any sense. It's not a paper that can possibly be accurate, because how much drug can really be getting into the [body systemically] that could be causing an increased rate of death?" Alexander said. "But we've read the paper. And the problem, if you want to say it's a problem, is that it's a good paper. It's a meta-analysis. It's got 4,600 people. It's all from randomized, controlled trials. It's all patients that have either critical limb ischemia or claudication — so, lower-extremity arterial disease. And the results are kind of stark."

What the study found

Study authors analyzed 28 clinical trials published between 2011 and 2018 and found no mortality difference before two years.

However, at two years post-implant, 7.2 percent of the patients who had devices coated with paclitaxel had died, vs. 3.8 percent of the control-group patients whose devices were not coated with the anti-inflammatory drug.

In the three papers with five-year data, the difference was even more stark, with a 14.7 percent risk of death in the paclitaxel group vs. 8.1 percent without it.

Lead study author Dr. Konstantinos Katsanos has said the statistical significance of the finding "is too strong to be ignored," even though the paper offers no clear theory on how the doses of paclitaxel from medical devices could be affecting the risk of death years after it's been used.

The drug has been used in heart devices and as a chemotherapy agent, and the same effects have not been documented in those populations.

The U.S. Food and Drug Administration last week announced that it was investigating the issue. The FDA does not recommend stopping all use of the devices but says patients should be informed of their risks and benefits.

The FDA will be re-examining data the companies provided for device approval, as well as looking at fresh long-term data provided by the companies in response to the JAHA report.

The agency review will focus on determining individual patients' causes of death and their unique health circumstances in the hopes of finding larger trends that weren't initially visible to researchers because of limitations in the data.

The paper in JAHA examined "all-cause" mortality, meaning that all deaths were counted whether the person died in a car accident or if they had a cardiac event tied to paclitaxel toxicity. The paper also lacks specificity on the paclitaxel doses received by individual patients.

In addition to the ongoing FDA review, several medical device companies including Medtronic and Boston Scientific will be presenting new data Tuesday at the industry meeting in Germany.

Other data will be reviewed at a meeting in Washington, D.C., in March.

Joe Carlson • 612-673-4779