Dive brief:

• A real world study of paclitaxel-coated stents and balloons used to treat peripheral artery disease in the legs found no evidence of harm associated with the devices, appearing to contradict an earlier mortality signal from a meta-analysis that FDA recommended physicians factor into treatment decisions.
• The researchers noted several limitations to the new study, including a shorter followup time of 2.72 years than the meta-analysis, in which the mortality signal was most apparent in the fourth and fifth years. The findings were presented Sunday at the American College of Cardiology's virtual meeting and published in JAMA Internal Medicine.
• In an accompanying editorial, the editor and deputy editor of JAMA Internal Medicine focused on the above-50% mortality rates in the new study's two patient groups. "While this well-done observational study provides new information on the association of paclitaxel stents with mortality, a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization with any devices," they wrote.

Dive Insight:

The device safety signal in the controversial 2018 meta-analysis, which was published in the Journal of the American Heart Association, created concerns for patients, clinicians, manufacturers and regulators. The signal of harm associated with the drug-coated devices was replicated in an internal meta-analysis by the FDA.

The safety worries prompted FDA to convene a hearing of its Circulatory System Devices Panel Advisory Committee, which recommended new labeling to warn physicians and patients of a potential long-term mortality risk associated with the products. Still, the advisory panel agreed the devices offer benefits to patients, including preventing amputation, and should stay on the market.

Five manufacturers, BD, Boston Scientific, Cook Medical, Medtronic and Philips, argued that there was insufficient evidence to blame paclitaxel for the heightened mortality signal. Companies offered their own data that showed no significant differences in survival rates among patients followed. But sales of the products declined.

FDA approved label revisions for the devices addressing the concern over long-term harm and recommended further research into the issue. The assessment published this weekend is the first report from the Safety Assessment Of Femoropopliteal Endovascular Treatment With Paclitaxel-coated Devices, or SAFE-PAD, study, conducted by researchers at the Smith Center for Outcomes Research in Cardiology in Boston and Beth Israel Deaconess Medical Center, and developed with input from FDA.

The study evaluated 168,553 Medicare beneficiaries ages 66 and older treated with a drug-coated or non-drug-coated device between 2015 and 2018. The incidence of mortality was 55.06% with non-drug-coated devices and 53.75% with drug-coated devices. The researchers found that peripheral drug-coated devices were noninferior for mortality to non-drug-coated devices, concluding there was no evidence of harm associated with the drug-coated devices.

In their related editorial, JAMA Internal Medicine Editor Rita Redberg of the University of California, San Francisco, Department of Medicine and Deputy Editor Mary McDermott of Northwestern University Feinberg School of Medicine said that while the SAFE-PAD analysis did not confirm the earlier signal of harm associated with paclitaxel-coated devices, it raises new and important questions about the high mortality rates in Medicare beneficiaries with PAD undergoing endovascular revascularization.

Physicians should continue to follow clinical practice guidelines that recommend conservative measures such as smoking cessation, exercise and medical therapy before endovascular revascularization for PAD patients, the editors said.

The SAFE-PAD researchers said the study is ongoing and will continue the safety evaluation of the devices until the median follow-up of all patients surpasses five years. The study may also serve as an example of how to use real-world evidence in making device safety evaluations, the researchers said.