SAFE PAD: Paclitaxel-coated devices noninferior to uncoated devices for mortality
Click Here to Manage Email Alerts
ATLANTA — An analysis of 160,000 Medicare beneficiaries demonstrated the noninferiority of paclitaxel-coated devices for mortality compared with uncoated devices for the treatment of peripheral artery disease, a speaker reported.
In the analysis, presented at the Society for Cardiovascular Angiography and Interventions Scientific Sessions by Eric A. Secemsky, MD, MSc, RPVI, FACC, FSCAI, FSVM, director of vascular intervention at Beth Israel Deaconess Medical Center, director of vascular research at the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology and assistant professor of medicine at Harvard Medical School, researchers observed no difference in mortality out to 5 years following femoropopliteal artery revascularization using paclitaxel-coated devices compared with uncoated devices.
The study was simultaneously published in Circulation: Cardiovascular Interventions.
“We’ve been dealing with this in the peripheral space since December 2018, when a meta-analysis was presented in JAHA,” Secemsky said during a presentation. “But there were a lot of limitations in these data. One big issue was more than 15% to 30% of the data were missing, and thus, a lot of the assumptions made here were probably flawed. However, the FDA responded swiftly, and we’ve been stuck in this limbo.”
As Healio previously reported, the meta-analysis by Konstantinos Katsanos, MD, PhD, MSc, EBIR, of the department of interventional radiology at Patras University Hospital in Rion, Greece, and colleagues, identified increasing mortality risk over 5 years of follow-up, prompted debate and caused a temporary halt to enrollment in two ongoing trials.
As a result, the FDA issued a series of recommendations that advised clinicians to discuss the potential benefits and risks tied to paclitaxel-coated devices and ensure patients are on optimal medical therapy and following appropriate lifestyle practices. The agency also stated that clinical studies of the drug-coated devices should continue.
Therefore, Secemsky and colleagues conducted a prespecified analysis, designed with FDA feedback, to assess the primary outcome of all-cause mortality among 168,553 Medicare beneficiaries who underwent femoropopliteal artery revascularization with a drug-eluting stent or drug-coated balloon compared with bare-metal stents or percutaneous transluminal angioplasty from April 2015 to December 2018 (mean age, 77 years; 45% women; 82% white; 46.7% with critical limb ischemia). Patients were followed through July 21, 2021 (median follow-up, 3.5 years). Baseline characteristics were similar between patients who did and did not receive a drug-coated device.
“If we did a randomized control trial powered for 4- to 5-year mortality, we’d need between 20,000 and 40,000 patients, which would be by far and away the largest peripheral study ever, and also have to exclude everybody already treated with paclitaxel-coated devices, which had been the standard of care up to that point,” Secemsky said. “We were charged to design a real-world study for the FDA and our peers to examine the safety of paclitaxel devices using the Medicare database.”
Among 32,000 patients with at least 5 years of follow-up data, the researchers observed no significant difference in all-cause mortality between uncoated (63.6%) and coated devices (62.5%; HR = 0.98; 95% CI, 0.96-0.99; P for noninferiority < .0001).
Following an instrumental variable analysis, Secemsky and colleagues observed no difference in mortality risk between coated and uncoated devices at 1 year (P for noninferiority = .015) and through 5 years of follow-up (P for noninferiority < .01).
In a sensitivity analysis using the negative control endpoints of acute MI, congestive HF and pneumonia, the researchers observed a negligible risk with paclitaxel devices compared with uncoated devices.
Drug-coated devices were similarly safe in terms of mortality among a subgroup of 4,212 low risk patients with no more than two comorbidities and no history of CLI (HR = 0.98; 95% CI, 0.87-1.1). The longest follow-up in this subgroup was 6.31 years.
The results were comparable across all other prespecified subgroups.
“It’s about time we update the most recent regulatory communications about paclitaxel-coated peripheral devices,” Secemsky said. “We now have a number of both prospective randomized trial data and observational data, and we are yet to be able to replicate the harm associated with paclitaxel in any of the subsequent studies that have come out since the December 2018 meta-analysis.”
Reference:
Collapse
Secemsky EA, et al. Featured Clinical Research: Part 2. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 19-22, 2022; Atlanta.
Click Here to Manage Email Alerts