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

Background-Several randomized controlled trials (RCTs) have already shown that paclitaxel-coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularization after lower extremity interventions. Methods and Results-A systematic review and meta-analysis of RCTs investigating paclitaxel-coated devices in the femoral and/or popliteal arteries was performed. The primary safety measure was all-cause patient death. Risk ratios and risk differences were pooled with a random effects model. In all, 28 RCTs with 4663 patients (89% intermittent claudication) were analyzed. All-cause patient death at 1 year (28 RCTs with 4432 cases) was similar between paclitaxel-coated devices and control arms (2.3% versus 2.3% crude risk of death; risk ratio, 1.08; 95% CI, 0.72-1.61). All-cause death at 2 years (12 RCTs with 2316 cases) was significantly increased in the case of paclitaxel versus control (7.2% versus 3.8% crude risk of death; risk ratio, 1.68; 95% CI, 1.15-2.47; -number-needed-to-harm, 29 patients [95% CI, 19-59]). All-cause death up to 5 years (3 RCTs with 863 cases) increased further in the case of paclitaxel (14.7% versus 8.1% crude risk of death; risk ratio, 1.93; 95% CI, 1.27-2.93; -number-needed-to-harm, 14 patients [95% CI, 9-32]). Meta-regression showed a significant relationship between exposure to paclitaxel (dose-time product) and absolute risk of death (0.4 +/- 0.1% excess risk of death per paclitaxel mg-year; P<0.001). Trial sequential analysis excluded false-positive findings with 99% certainty (2-sided alpha, 1.0%). Conclusions-There is increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs. Further investigations are urgently warranted.