Another metaanalysis done by Katsanos et al. (1) from eight randomized trials show that amputation free survival was worse with Paclitaxel coated balloon (PCB) in infrapopliteal arteries for the treatment of critical limb ischemia. Authors also, show that the harm signal was evident when examining the high dose (3.0-3.5 micrograms/mm2) device and attenuated below significance in case of a low-dose (2 micrograms/mm2) device.
Prior metanalysis done by the same research group (2) has raised major concerns about the safety profile of paclitaxel in the lower extremity peripheral vascular disease by showing increased mortality at 2 and 5 years (2). Following this publication, the FDA recommended to, “discuss the risks and benefits of all available peripheral arterial disease treatment options with patients (3). “
In this study, authors have pooled 8 randomized clinical trials, out of which three were recently presented at international meetings. The results of these trials, SINGA-PACLI, ACOART BTK, ACOART II are not published yet. Different types of PCBs are used in these 8 studies (IN. PACT Amphirion, Passeo-18 Lux, Luminor 14, Passeo-18 Lux, Litos, Lutnoix).
In this metanalysis, authors have shown that amputation free survival was significantly worse with PCB, 13.7% crude risk of death or limb loss, compared to 9.4% in case of uncoated balloon angioplasty (HR 1.52, 95% CI 1.12-2.07, p=0.08). TLR was significantly reduced with PCB (11.8% vs. 25.6%, RR 0.53, 95% CI 0.35-0.81, p=0.004). Authors have also performed dose-response analysis and found that amputation free-survival was significantly high when high dose (3.0-3.5 micrograms/mm2) device was used (HR 1.62, 95% CI (1.16-2.27) and attenuated below significant in case of a low-dose (2 micrograms/mm2) device. (HR 1.06 (0.48-2.34).
Authors have stated the same limitations as prior study as it is a study-level meta-analysis and individual patient level details were not available. Follow-up beyond 1-year was not available in the studies and effect sizes when comparing high-dose and low-dose were different.
Authors conclude that there is risk of mortality or major limb loss during the first year with paclitaxel-coated balloon even in the infrapopliteal arteries for critical limb ischemia treatment and recommend further large size multicenter studies with longer-term follow-up.
- Risk of Death and Amputation with Use of Paclitaxel-Coated Balloons in the Infrapopliteal Arteries for Treatment of Critical Limb Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Katsanos, Konstantinos et al. Journal of Vascular and Interventional Radiology. Published online.
- Katsanos, K., Spiliopoulos, S., Kitrou, P., Krokidis, M., Karnabatidis, D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7: e011245