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.

Purpose To report the 6-month results of a prospective randomized trial investigating angioplasty with paclitaxel-coated balloons (PCB) vs. plain balloon angioplasty (BA) for the treatment of failing native arteriovenous fistulae (AVF) or prosthetic arteriovenous grafts (AVG). Methods The enrollment criteria for this non-inferiority hypothesis trial included clinical signs of failing dialysis access with angiographic documentation of a significant venous stenotic lesion in patients with AVF or AVG circuits. From March to December 2010, 40 patients (29 men; mean age 64.1±14.3 years) were randomized to undergo either PCB dilation (n=20) or standard BA (n=20) of a stenosed venous outflow lesion. Regular angiographic follow-up was scheduled bimonthly. Study outcome measures included device success (<30% residual stenosis without postdilation), procedural success (<30% residual stenosis), and primary patency of the treated lesion (<50% angiographic restenosis and no need for any interim repeat procedures). Results Baseline and procedural variables were comparably distributed between both groups. Device success was 9/20 (45%) for the PCB device vs. 20/20 (100%) for standard control BA (p<0.001). Procedural success was 100% in both groups after further high-pressure post-dilation as necessary. There were no major or minor complications in either group. At 6 months, cumulative target lesion primary patency was significantly higher after PCB application (70% in PCB group vs. 25% in BA group, p<0.001; HR 0.30, 95% CI 0.12 to 0.71, p<0.006). Conclusion PCB angioplasty improves patency after angioplasty of venous stenoses of failing vascular access used for dialysis.

The optimal transcatheter embolization strategy for patients with unresectable hepatocellular carcinoma (HCC) remains elusive. We conducted a systematic review and network meta-analysis (NMA) of different embolization options for unresectable HCC. Medical databases were searched for randomized controlled trials evaluating bland transarterial embolization (TAE), conventional TACE, drug-eluting bead chemoembolization (DEB-TACE), or transarterial radioembolization (TARE), either alone or combined with adjuvant chemotherapy, or local liver ablation, or external radiotherapy for unresectable HCC up to June 2017. Random effects Bayesian models with a binomial and normal likelihood were fitted (WinBUGS). Primary endpoint was patient survival expressed as hazard ratios (HR) and 95% credible intervals. An exponential model was used to fit patient survival curves. Safety and objective response were calculated as odds ratios (OR) and accompanying 95% credible intervals. Competing treatments were ranked with the SUCRA statistic. Heterogeneity-adjusted effective sample sizes were calculated to evaluate information size for each comparison. Quality of evidence (QoE) was assessed with the GRADE system adapted for NMA reports. All analyses complied with the ISPOR-AMCP-NCP Task Force Report for good practice in NMA. The network of evidence included 55 RCTs (12 direct comparisons) with 5,763 patients with preserved liver function and unresectable HCC (intermediate to advanced stage). All embolization strategies achieved a significant survival gain over control treatment (HR range, 0.42–0.76; very low-to-moderate QoE). However, TACE, DEB-TACE, TARE and adjuvant systemic agents did not confer any survival benefit over bland TAE alone (moderate QoE, except low in case of TARE). There was moderate QoE that TACE combined with external radiation or liver ablation achieved the best patient survival (SUCRA 86% and 96%, respectively). Estimated median survival was 13.9 months in control, 18.1 months in TACE, 20.6 months with DEB-TACE, 20.8 months with bland TAE, 30.1 months in TACE plus external radiotherapy, and 33.3 months in TACE plus liver ablation. TARE was the safest treatment (SUCRA 77%), however, all examined therapies were associated with a significantly higher risk of toxicity over control (OR range, 6.35 to 68.5). TACE, DEB-TACE, TARE and adjuvant systemic agents did not improve objective response over bland embolization alone (OR range, 0.85 to 1.65). There was clinical diversity among included randomized controlled trials, but statistical heterogeneity was low. Chemo- and radio-embolization for unresectable hepatocellular carcinoma may improve tumour objective response and patient survival, but are not more effective than bland particle embolization. Chemoembolization combined with external radiotherapy or local liver ablation may significantly improve tumour response and patient survival rates over embolization monotherapies. Quality of evidence remains mostly low to moderate because of clinical diversity. CRD42016035796 (http://www.crd.york.ac.uk/PROSPERO).

Purpose: To report a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons (PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each other in the infrapopliteal arteries. Methods: Sixteen RCTs comprising 1805 patients with 1-year median follow-up were analyzed. Bayesian random effects binomial models were employed (WinBUGS). Relative treatment effects were expressed as odds ratios (ORs) with 95% credible intervals (CrI), and the cumulative rank probabilities were calculated to provide hierarchies of competing treatments. Quality of evidence (QoE) was assessed with the GRADE (grading of recommendations assessment, development, and evaluation) system. Sensitivity, heterogeneity, and consistency analyses were performed. Results: There was high QoE that infrapopliteal DES significantly reduced restenosis compared with BMS (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95% CrI 0.11 to 0.45). Likewise, DES significantly reduced target lesion revascularization (TLR) compared with BA (OR 0.41, 95% CrI 0.22 to 0.75) and BMS (OR 0.26, 95% CrI 0.15 to 0.45). Paclitaxel-coated balloons also reduced TLR compared with BA (OR 0.55, 95% CrI 0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18 to 0.67), but QoE was low to moderate. BA had lower TLR than BMS (OR 0.63, 95% CrI 0.40 to 0.99) with high QoE. DES was the only treatment that significantly reduced limb amputations compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB (OR 0.51, 95% CrI 0.26 to 0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with moderate to high QoE. DES also significantly improved wound healing compared with BA (OR 2.02, 95% CrI 1.01 to 4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with high QoE. Results were stable on sensitivity and meta-regression analyses without any significant publication bias or inconsistency. Conclusion: Infrapopliteal DES were associated with significantly lower rates of restenosis, TLR, and amputations and improved wound healing compared to BA and BMS. DES also significantly reduced amputations compared with PCB.