ATLANTA — Paclitaxel-coated devices for femoropopliteal artery revascularization were not associated with any excess mortality risk in the latest update from Medicare data.
The risk of death from any cause, if anything, trended slightly lower (hazard ratio 0.98, 95% CI 0.96-0.99) with paclitaxel-eluting stents or -coated balloons compared with bare metal stent or percutaneous transluminal angioplasty (PTA) during a median follow-up of 3.52 years in more than 160,000 individuals, reported Eric A. Secemsky, MD, MSc, of Beth Israel Deaconess Medical Center in Boston.
Weighted cumulative mortality in up to 6.31 years of follow-up occurred in 62.5% of patients treated with paclitaxel-coated devices versus 63.6% with non-coated devices, which met non-inferiority criteria, he said at the Society for Cardiovascular Angiography and Interventions (SCAI) annual meeting. The findings were published simultaneously in a research letter in Circulation: Cardiovascular Interventions.
The results largely match earlier data from the same cohort in the SAFE-PAD study at 2 years and a number of other smaller observational cohorts.
“We’ve been dealing with this in the peripheral space since December 2018, when this meta-analysis was presented,” Secemsky noted at the SCAI featured clinical research session. That meta-analysis of randomized trials suggested a 68% relative jump in mortality with paclitaxel devices for peripheral artery disease (PAD) at 2 years and 93% at 4 to 5 years, albeit based on just three trials at that point with less than 1,000 patients.
FDA’s response, recommending only cautious use of paclitaxel-coated devices for PAD, has left the field in “limbo” ever since, Secemsky said.
“We haven’t been able to replicate that signal of harm in any of the subsequent studies that have come out,” he concluded. “It’s about time that we revisit the most recent regulatory communications about paclitaxel-coated peripheral devices.”
SCAI session panelist Herb D. Aronow, MD, MPH, of Henry Ford Health in Royal Oak, Michigan, agreed.
“It’s clear that a randomized trial is not going to happen,” he said. “It doesn’t seem like the data can get any better than what you just presented … Really, this is a very sophisticated analysis you’ve done, and I think it’s as convincing as anything. My conclusion as an operator is, it’s time to move on.”
Secemsky noted that his conversations with FDA suggest the agency is ready to move on too, but is still waiting on one final piece of data, an updated patient-level meta-analysis sponsored by industry.
“In reality, I think some of the pressure is going to have to come from us,” he said. The multi-society response at the FDA advisory panel in 2019 on this issue “made a huge impact at the time, and I think it’s time for us to do something like that.”
The SAFE-PAD study included all 168,553 Medicare fee-for-service beneficiaries who had femoropopliteal artery revascularization from April 2015 through December 2018 with a drug-eluting stent, drug-coated balloon, bare metal stent, or PTA. Patients had to have been enrolled in Medicare for at least a year prior to the procedure, to ascertain comorbidities.
None of the prespecified subgroups showed harm from paclitaxel-coated device use, including low-risk patients, those with critical limb ischemia or not, those with stents implanted, or those who only had balloon angioplasty.
Instrumental variable analyses were likewise consistent with the overall results.
A falsification analysis turned up “negligible” associations with acute myocardial infarction, heart failure, and pneumonia, further supporting the robust results of the main analysis.
While it was important to confirm lack of risk in the healthiest patients, SCAI president and session co-moderator Timothy Henry, MD, of The Christ Hospital in Cincinnati, noted that it’s plausible to believe that use of these devices could actually result in a mortality benefit in the sickest patients, like those with critical limb ischemia (CLI), for whom treatment should improve activity and thus survival. He pointed to the subgroup analysis in which the CLI patients had an HR 0.96 (95% CI 0.95-0.98) for mortality with paclitaxel-coated devices.
It’s worth revisiting once the dust settles, Secemsky agreed.
Secemsky disclosed funding from the National Heart, Lung, and Blood Institute, Harvard Medical School and the University of California San Francsico, grants to his institution from AstraZeneca, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic, and Philips, and consulting or speaking fees from Abbott, BD, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Philips.