In June 2023, the Cardiovascular Interventional Radiological Society of Europe (CIRSE) published an editorial in Cardiovascular Interventional Radiology (CVIR). Written on behalf of CIRSE’s Endovascular Subcommittee, the authors “advocate that the benefits of paclitaxel-coated device used in the femoropopliteal segment in terms of increased primary patency and reduced TLR [target lesion revascularisation] warrant their use in the routine treatment of patients with femoropopliteal disease”. The editorial was published this week in the wake of the US Food and Drug Administration (FDA) letter stating that the data do not show that paclitaxel-coated devices come with an excess mortality risk.
The authors, including corresponding author Robert Morgan (St George’s University Hospitals NHS Foundation Trust, London, UK) begin their editorial by outlining the background to the controversy around use of paclitaxel-coated balloons and paclitaxel-eluting stents. They reference initial “encouraging data” that led to “increasingly widespread” recourse to drug-based therapies to treat peripheral arterial disease (PAD) in femoropopliteal disease up until Katsanos et al published their meta-analysis in 2018. The findings of this meta-analysis—that all-cause mortality following treatment with paclitaxel-coated balloons and paclitaxel-eluting stents in the femoropopliteal segment in claudicants was 14.7% at five years, with the rate post-percutaneous transluminal angioplasty (PTA) calculated as 8.1%—“resulted in a metaphorical tsunami destroying confidence worldwide in paclitaxel” as safe for preventing restenosis.
Morgan et al outline that after the Katsanos meta-analysis was published, the US FDA created an expert panel to provide updates to healthcare providers. Other national medical regulators also made recommendations in light of the findings to be “[cautious]” in using paclitaxel, with the UK Medicines and Healthcare Products Regulatory Agency (MHRA) among those advocating for limiting its use to patients with chronic limb-threatening ischaemia (CLTI) only. This reduction in use of paclitaxel in these settings led to the “loss of the proven benefits of drug-based device therapies to patients in terms of reduced patency of femoropopliteal angioplasty and stenting using non-paclitaxel-coated devices, and probably an associated increase in the need for hospital readmission rates for repeat revascularisation procedures”.
The editorial proceeds to highlight the findings of a subsequent meta-analysis based on the same randomised trials included by Katsanos et al: “that there is a minimal or no increase in mortality associated with paclitaxel-coated devices. Moreover, when the patient-level data of the trials used for the Katsanos meta-analysis were assessed, the absolute increased mortality risk associated with paclitaxel use at five years decreased from 14.7 to 4.6%”. Morgan et al suggest that the difference in these reported outcomes could be attributed to different study designs and data sources, among other factors.
“One major flaw” in the conclusions reached by Katsanos, the CIRSE editorial opines, is that “none of [the trials included in the meta-analysis] were designed to assess for a difference in mortality between the patient groups”. Morgan et al also list various studies post-Katsanos that suggest paclitaxel to be “associated with improved efficacy but was not associated with increased mortality” (the full list can be found in the footnotes of the CVIR publication here).
Rounding off their editorial, the CIRSE authors point out that “a robust body of evidence now exists to refute the existence of a long-term mortality signal associated with paclitaxel-coated devices i.e. any mortality risk is negligible or absent”. They go further to conclude that “all efforts to find a link and a causal explanation for the perceived mortality risk between paclitaxel dose and mortality have failed”. Looking to the future, Morgan et al urge that “endovascular trial designs must incorporate strategies and methods to maximise patient retention and facilitate long-term assessment and reporting of vital statistics, including mortality”. In addition, they express their interest in seeing data on the efficacy of sirolimus-eluting devices and on the comparative efficacy of paclitaxel-coated versus sirolimus-eluting devices.
For the time being, as stated above, the authors support using paclitaxel-coated devices in the femoropopliteal segment to increase primary patency and reduce TLR in patients with femoropopliteal disease.