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

Abstract

Background Several randomized controlled trials ( RCT s) 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 RCT s 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 RCT s with 4663 patients (89% intermittent claudication) were analyzed. All‐cause patient death at 1 year (28 RCT s 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 RCT s 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 RCT s 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 α, 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. Clinical Trial Registration URL : www.crd.york.ac.uk/PROSPERO . Unique identifier: CRD 42018099447.

Drug‐coated balloon versus plain old balloon angioplasty in femoropopliteal disease: An updated meta‐analysis of randomized controlled trials

“…Our findings are consistent with findings from the IN PACT SFA trial which found no association between paclitaxel‐coated balloon use and mortality. Interestingly a recent meta‐analysis published by Katsanos et al compared paclitaxel devices (both stents and balloons) in FPD to nondrug‐coated treatment device and reported higher mortality both at 2‐year and 5‐year follow‐up. The analysis included 4,600 patients from 28 RCTs.…”

“…Revascularization of FPD with DCB has been shown to improve primary patency and reduces target lesion revascularization (TLR) . However, a recent study suggested that there may be increased all‐cause mortality in patients with FPD who are treated with paclitaxel devices (DCB and drug eluting stents) . Subsequently the Food and Drug Administration authored a letter to peripheral interventionalists and vascular medicine providers recommending surveillance of patients treated with paclitaxel devices and initiated a review of available data to determine if long‐term risks are present .…”

“…Considering the theoretical advantages of DCB and the numerous recent comparative studies of DCB versus POBA, we performed a systematic review and meta‐analysis of all available randomized controlled trials (RCTs) to date. The objective of this study is to analyze and update the available evidence comparing DCB to POBA with a focus on device‐related safety considering the recent report of increased mortality with paclitaxel‐coated devices …”

“…5,9 However, a recent study suggested that there may be increased all-cause mortality in patients with FPD who are treated with paclitaxel devices (DCB and drug eluting stents). 10 Subsequently the Food and Drug Administration authored a letter to peripheral interventionalists and vascular medicine providers recommending surveillance of patients treated with paclitaxel devices and initiated a review of available data to determine if long-term risks are present. 11 Considering the theoretical advantages of DCB and the numerous recent comparative studies of DCB versus POBA, we performed a systematic review and meta-analysis of all available randomized controlled trials (RCTs) to date.…”

Treatment of lower limb ischaemia in patients with diabetes

“…Drug‐eluting balloons (DEBs) may then be used for femoropopliteal lesions as they have been shown to significantly reduce binary restenosis, target lesion revascularization and improve primary patency rates. However there is a controversy regarding increased risk of death following the use of paclitaxel‐coated balloons and stents in the femoropopliteal artery of the lower limbs and the use of DEBs in BTK lesions have shown equivocal results.…”