What Now for the Endovascular Community After the Paclitaxel Mortality Meta-Analysis: Can Sirolimus Replace Paclitaxel in the Peripheral Vasculature?

Early (6 months) results of a pilot prospective study to investigate the efficacy and safety of sirolimus coated balloon angioplasty for dysfunctional arterio-venous fistulas: MAgicTouch Intervention Leap for Dialysis Access (MATILDA) Trial

“…However, this trend has never been shown in the AVF circuit from either the meta-analysis data [ 9 ] or from the larger RCTs [ 10 ] and registries [ 21 ]. If the current trend continues, paclitaxel devices may be ultimately consigned to the past [ 13 ] and this will be a setback for progress as many vascular specialists perceive CBA and bare metal stents to be basic technologies with poorer outcomes. The mortality rate of 12.1% (4 deaths) all from cardiovascular-related causes may seem slightly alarming but these are patients with multiple co-morbidities and vascular risk factors.…”

“…Furthermore, recent attention has been drawn to a possible increase in late mortality signal [ 11 ] and lower amputation free survival [ 12 ] in patients receiving DCB treatment with paclitaxel for peripheral arterial disease, although this suggestion has not been demonstrated in the data of DCB within the fistula circuit either at 1 or 2 years [ 9 , 10 ]. In light of these concerns, attention has turned away recently from paclitaxel-based technologies to sirolimus coated platforms [ 13 ]. Sirolimus, like paclitaxel, is a potent antiproliferative agent, which has been found to prevent restenosis in the coronary bed [ 14 ] and more recently in the peripheral vasculature [ 15 ] but to date has not been studied in AVF circuits.…”

Utility of sirolimus coated balloons in the peripheral vasculature – a review of the current literature

“…This was a problem especially for its use in the peripheral circulation, where ‘nude’ sirolimus application had slow tissue absorption, necessitating the use of a co-solvent to enhance tissue uptake (Tang et al 2020a ). Initial attempts also saw rapid deactivation of sirolimus molecules when delivered into aqueous media via sirolimus eluting stents in the superficial femoral artery (SFA), resulting in no or marginal benefit (Tang et al 2020a ).…”

“…However, the findings of the landmark meta-analysis by Katsanos et al (Katsanos et al 2018 ) in 2018 called in doubt the role and safety of the use of paclitaxel devices including PCB and stents, where it was suggested that there was an increase mortality in patients with femoropopliteal disease following treatment with paclitaxel devices in the medium term. This resulted in widespread alarm among the endovascular surgery community (Tang et al 2020a ), who have by that point assumed the safety of paclitaxel devices (Salisbury et al 2016 ) and considered it standard of care over POBA for the femoropopliteal region (Aboyans et al 2018 ; Feldman et al 2018 ). A subsequent study by Katsanos (Katsanos et al 2020 ) also demonstrated worse AFS with the use of PCB compared to POBA for below the knee (BTK) disease at 12 months.…”

“…A subsequent study by Katsanos (Katsanos et al 2020 ) also demonstrated worse AFS with the use of PCB compared to POBA for below the knee (BTK) disease at 12 months. While several justifications have been offered to cast doubt on the findings of the meta-analysis (Tang et al 2020a ; Soon et al 2020 ), such as the lack of standardized endpoints, poor handling of outcomes, lack of long-term data and insufficient statistical power, sufficient damage has been done, with the Food and Drug Administration (FDA) in the United States eventually publishing a provisional warning on the use of paclitaxel devices pending further recommendation (Update 2019 ).…”