FDA: Reduce use of paclitaxel devices in PAD until mortality signal clarified

Issue: April 2019

The FDA warned in March that using paclitaxel-coated products in the treatment of peripheral arterial disease in the femoropopliteal artery may increase mortality risk.

“Because of this concerning safety signal, we believe alternative treatment options should generally be used for most patients while we continue to further evaluate the increased long-term mortality signal and its impact on the overall benefit-risk profile of these devices,” the agency wrote in the safety communication, noting exceptions can be made for patients at very high risk for restenosis.

The announcement came after an FDA official reported at the Vascular Leaders Forum that the agency’s preliminary analysis of the possible link between paclitaxel-coated devices and mortality showed a signal of a link between the two, but no “smoking gun” to provide definitive proof or pinpoint a cause.

Also at the meeting, VIVA Physicians announced it will conduct and fund a patient-level meta-analysis to determine whether aggregated findings from summary-level data hold up when patient-level data are aggregated.

As Cardiology Today previously reported, a summary-level meta-analysis published in the Journal of the American Heart Association by Konstantinos Katsanos, MD, PhD, MSc, EBIR, of the department of interventional radiology at Patras University Hospital in Rion, Greece, and colleagues found that patients with peripheral artery disease receiving paclitaxel-coated balloons or stents had higher mortality risk at 2 and 5 years compared with controls. The analysis prompted two trials of paclitaxel-coated devices to be paused, the FDA to launch its investigation and the manufacturers of the devices to make their trial data available for independent researchers to conduct patient-level analyses.

FDA investigation

Misti Malone, PhD, chief of the peripheral interventional devices branch of the FDA’s Center for Devices and Radiological Health, said the FDA’s investigation is aimed to confirm the results of the JAHA meta-analysis with all 28 trials included in the meta-analysis and then evaluating all available long-term U.S. and global randomized controlled trial data

In its safety communication, the FDA stated it will convene its Circulatory System Devices Panel for advice on the topic.

Patient-level meta-analysis

During the forum, Krishna Rocha-Singh, MD, FACC, FAHA, chief scientific officer for the Prairie Heart Institute of Illinois at St. John’s Hospital in Springfield, Illinois, announced that VIVA Physicians will conduct and fund a meta-analysis using independent patient data, “the new gold standard for data synthesis.”

In an interview with Cardiology Today after the FDA alert, Rocha-Singh said that “as cardiologists, we understand that the FDA is tasked with the safety of medical devices, and they saw a statistical safety signal, so I think they are well within their purview to recommend against using paclitaxel-coated devices in most patients with PAD until we learn more. I do think it’s a bit hyperbolic, however, to suggest that insurance agencies will stop reimbursing for use of these devices and that medicolegal issues should drive the issue as to whether physicians chose to use these devices in the best interest of their patients.” – by Erik Swain

References:
Malone M. The FDA interpretation of the meta-analysis and what we are looking for with the data we requested.
Rocha-Singh K. The power of combining patient-level data. Both presented at: Vascular Leaders Forum; March 1-2, 2019; Washington, D.C.
Katsanos K, et al. J Am Heart Assoc. 2018;doi:10.1161/JAHA.118.011245.

Disclosures: Malone reports she is an employee of the FDA. Rocha-Singh reports he is a consultant for Medtronic.