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.

A formal systematic review and study-level meta-analysis of randomized controlled trials investigating treatment of the infrapopliteal arteries with paclitaxel-coated balloons compared with conventional balloon angioplasty for critical limb ischemia (CLI) was conducted. Medical databases and online content were last screened in September 2019. The primary safety and efficacy endpoint was amputation-free survival defined as freedom from all-cause death and major amputation. Target lesion revascularization (TLR) constituted a secondary efficacy endpoint. Summary effects were synthesized with a random-effects model. Some 8 randomized controlled trials with 1,420 patients (97% CLI) were analyzed up to 1 year follow-up. Amputation-free survival was significantly worse in case of paclitaxel (13.7% crude risk of death or limb loss compared to 9.4% in case of uncoated balloon angioplasty; hazard ratio 1.52; 95% confidence interval: 1.12-2.07, p = .008). TLR was significantly reduced in case of paclitaxel (11.8% crude risk of TLR versus 25.6% in control; risk ratio 0.53; 95% confidence interval: 0.35-0.81, p = .004). The harm signal was evident when examining the high-dose (3.0-3.5 μg/mm2) devices, but attenuated below significance in case of a low-dose (2.0 μg/mm2) device. Actual causes remain largely unknown, but non-target paclitaxel embolization is a plausible mechanism.