Response to “Re Risk of Major Amputation Following Application of Paclitaxel Coated Balloons in the Lower Limb Arteries: a Systematic Review and Meta-Analysis of Randomised Controlled Trials”

We thank Dr Coscas and colleagues for their interest in our recent paper documenting a substantially higher risk of major amputation following use of paclitaxel coated balloons in the infra-inguinal arteries. The authors discuss the fact that the control arm in the PACUS trial had also received liquid paclitaxel at the treatment site. We would like to clarify that this has been noted and accounted for in our meta-analysis. First, as explained in the legend of Table 1, in the PACUS trial, DCB were randomised vs. a combination of high frequency low intensity intravascular ultrasound therapy and contrast dissolved liquid paclitaxel (1.0 μg/mm³) delivered in the femoropopliteal treatment area under distal balloon occlusion and aspirated with a 50 mL syringe after 60 sec. Second, the total dose of liquid paclitaxel in the control arm was accounted for in the multivariable dose response meta-analysis, that is the control liquid paclitaxel dose was incorporated in the reference control arm when the amputation log hazard was regressed on the nominal paclitaxel dose delivered from the DCB devices. Of note, the dose response meta-analysis demonstrated an accelerated amputation risk over increasing paclitaxel dose. Finally, in the sensitivity tests, the pooled HR was congruent across leave one out meta-analysis without any influential studies. The pooled estimate was HR 1.55 (95% CI 1.06 – 2.26; p = .025) when excluding the PACUS trial. Hence, the authors believe that the current findings are stable and robust.