Stavros Spiliopoulos

Paclitaxel-Coated Balloon Angioplasty vs. Plain Balloon Dilation for the Treatment of Failing Dialysis Access: 6-Month Interim Results From a Prospective Randomized Controlled Trial:

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.

Primary Everolimus-Eluting Stenting Versus Balloon Angioplasty With Bailout Bare Metal Stenting of Long Infrapopliteal Lesions for Treatment of Critical Limb Ischemia

Purpose: To report the long-term outcomes of a single-center prospective study investigating primary placement of everolimus-eluting metal stents for recanalization of long infrapopliteal lesions compared to a matched historical control group treated with plain balloon angioplasty and provisional placement of bare metal stents in a bailout manner. Methods: The study included 81 patients (63 men; mean age 71 years, range 45–85) suffering from critical limb ischemia (CLI) and angiographically proven long-segment (at least 1 lesion >4.5 cm) de novo infrapopliteal artery disease who underwent below-the-knee revascularization with either primary placement of everolimus-eluting stents (n = 47, 51 limbs, 102 lesions) or angioplasty and bailout bare metal stenting (n=34, 36 limbs, 72 lesions). Clinical and angiographic follow-up was collected at regular time intervals. Primary clinical and angiographic endpoints included patient survival, major amputationfree survival, angiographic primary patency, angiographic binary restenosis (>50%), and overall event-free survival. Results were stratified according to endovascular treatment received. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity. Results: Baseline demographics were well matched. No significant differences were identified between the 2 groups with regard to overall 3-year patient survival (82.2% versus 65.7%; p=0.90) and amputation-free survival (77.1% versus 86.9%; p=0.20). Up to 3 years, lesions fully covered with everolimus-eluting stents were associated with significantly higher primary patency [hazard ratio (HR) 7.98, 95% CI 3.69 to 17.25, p<0.0001], reduced binary restenosis (HR 2.94, 95% CI 1.74 to 4.99, p<0.0001), and improved overall event-free survival (HR 2.19, 95% CI 1.16 to 4.13, p=0.015) versus the matched historical control group. Conclusion: Primary infrapopliteal everolimus-eluting stenting for CLI treatment significantly inhibits restenosis and improves long-term angiographic patency and overall patient event-free survival compared to balloon angioplasty and bailout bare metal stenting.

Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting stents, and drug-coated balloons in the femoropopliteal artery

OBJECTIVE Several randomized controlled trials (RCTs) have shown the superiority of some of these technologies over balloon angioplasty, but direct comparisons between these treatment options are lacking. The authors conducted a network meta-analysis of RCTs comparing bare nitinol stents, covered nitinol stents, paclitaxel- or sirolimus-eluting stents (PES or SES), and paclitaxel-coated balloons (PCB) with plain balloon angioplasty or with each other in the femoropopliteal artery (PROSPERO registry: CRD42013004845). METHODS Sixteen RCTs comprising 2532 patients with 4227 person-years of follow-up were analyzed on an intention-to-treat basis. Bayesian random effects Poisson and binomial models were used for mixed treatment comparisons (WinBUGS). Clinical heterogeneity was accounted for by incorporating a meta-regression model on trial-specific baseline risk. End points included technical success, vascular restenosis, target lesion revascularization, and major amputations. Pairwise odds ratios and rate ratios (ORs and RRs) of absolute treatment effects were calculated, and the probabilities of each treatment being best are reported. Summary estimates are reported as the posterior median and associated credible intervals (CrIs) that serve the same purpose as confidence intervals in the context of the Bayesian framework. Extensive sensitivity, meta-regression, and network consistency analyses were performed to evaluate heterogeneity. RESULTS Technical success was highest with covered stents (pooled OR, 13.6; 95% CrI, 3.3-31.1, probability best 82%) followed by uncovered stents (pooled OR, 7.0; 95% CrI, 2.6-129, probability best 18%) when compared with balloon angioplasty (reference treatment). Vascular restenosis was lowest with PES (RR, 0.43; 95% CrI, 0.16-1.18, probability best 45%) followed by PCB (RR, 0.43; 95% CrI, 0.26-0.67, probability best 42%). Target lesion revascularization was lowest with PCB (RR, 0.36; 95% CrI, 0.23-0.55, probability best 56%) followed by PES (RR, 0.42; 95% CrI, 0.16-1.06, probability best 33%). Major amputations were rare in all treatment and control groups (pooled amputation rate of 0.7 events per 100 person-years). CONCLUSIONS Immediate technical success is better with the use of covered stents, whereas paclitaxel-eluting stents and paclitaxel-coated balloons offer the best long-term results in the femoropopliteal artery.

Incidence, anatomical location, and clinical significance of compressions and fractures in infrapopliteal balloon-expandable metal stents.

Purpose: To investigate the incidence, anatomical location, and clinical impact of fractures and/or compression of infrapopliteal balloon-expandable metal stents implanted for critical limb ischemia (CLI) treatment. Methods: This prospective study included 63 CLI patients (45 men; mean age 71.3±9.5 years) who had been treated with infrapopliteal angioplasty and stent placement for 191 lesions in 84 limbs. In all, 369 stents (296 stainless steel and 73 cobalt-chromium alloy) were implanted; 239 were placed overlapping in tandem lesions. Mean length of the overall stented segment was 4.4±6.3 cm (range 1.6–14.0). Stents were located in the tibioperoneal (n=34), anterior tibial (n=195), posterior tibial (n=63), and peroneal (n=77) arteries. Follow-up consisted of digital subtraction angiography and infrapopliteal radiography imaging at 2 different angles. Evaluation of stents for the presence of fracture and/or compression was done after digital processing at the highest possible magnification. Stent fractures were defined according to published standards, whereas compression was classified as severe shape alteration and/or collapse of the stent mesh. Angiographic restenosis was based on a 50% threshold. Results: Mean follow-up was 15±11 months (range 6–60). Image analysis detected 1 (0.3%) severe stent fracture (complete separation and misalignment of stent struts) and 11 (3.0%) stent compressions. Infrapopliteal stent fracture and compressions were associated with increased artery restenosis [100% (12/12) versus 47.3% (169/357), p<0.001] and an increased rate of clinical deterioration and clinically-driven reinterventions [41.7% (5/12 limbs) versus 19.4% (14/72 limbs), p=0.04]. The single fracture and most of the compressions were located in the distal third of the anterior tibial artery. Conclusion: Stent fractures and compressions of infrapopliteal balloon-expandable metal stents are infrequent. However, they may be related to increased restenosis.

Quality Improvement Guidelines for Percutaneous Catheter-Directed Intra-Arterial Thrombolysis and Mechanical Thrombectomy for Acute Lower-Limb Ischemia

Percutaneous catheter-directed intra-arterial thrombolysis is a safe and effective method of treating acute and subacute lower limb ischemia, as long as accurate patient selection and procedural monitoring are ensured. Although larger, controlled trials are needed to establish the role of PTDs in ALI, mechanical thrombectomy could currently be applied combined with lytic infusion in selected cases where rapid recanalization is required or as a stand-alone therapy when the administration of thrombolytic agents is contraindicated.

Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel-Coated Balloon Angioplasty in the Femoropopliteal Arteries: Role of Paclitaxel Dose and Bioavailability

Purpose: To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery. Methods: PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration’s tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO ). Results: Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1–11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference −0.89 mm, 95% CI −1.14 to −0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-μg and 3.5-μg) PCBs were significantly more effective compared with low-dose 2-μg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001). Conclusion: PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability.

Drug-eluting versus plain balloon angioplasty for the treatment of failing dialysis access: Final results and cost-effectiveness analysis from a prospective randomized controlled trial (NCT01174472)

OBJECTIVE To report the final results and cost-effectiveness analysis of a prospective randomized controlled trial investigating drug-eluting balloon (DEB) versus plain balloon angioplasty (BA) for the treatment of failing dialysis access (NCT01174472). METHODS 40 patients were randomized to angioplasty with either DEB (n=20) or BA (n=20) for treatment of significant venous stenosis causing a failing dialysis access. Both arteriovenous fistulas (AVF) and synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was scheduled every two months. Primary endpoints were technical success and target lesion primary patency at 1 year. Cumulative and survival analysis was performed. Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER) were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn. RESULTS Baseline variables were equally distributed between the two groups. At 1 year, cumulative target lesion primary patency was significantly higher after DEB application (35% vs. 5% after BA, p<0.001). Overall, median primary patency was 0.64 years in case of DEB vs. 0.36 years in case of BA (p=0.0007; unadjusted HR=0.27 [95%CI: 0.13-0.58]; Cox adjusted HR=0.23 [95%CI: 0.10-0.50]). ICER was 2198 Euros (€) per primary patency year of dialysis access gained. INB was 1068€ (95%CI: 31-2105€) for a willingness-to-pay (WTP) threshold of 5000€ (corresponding acceptability probability >97%). CONCLUSION DEB angioplasty may be a cost-effective option that significantly improves patency after angioplasty of venous stenoses of failing vascular dialysis access. Further large-scale randomized trials are warranted.

Paclitaxel-coated versus plain balloon angioplasty for dysfunctional arteriovenous fistulae: one-year results of a prospective randomized controlled trial.

PURPOSE To report 1-year results of a single-center randomized controlled trial comparing paclitaxel-coated balloon (PCB) versus high-pressure plain balloon angioplasty for the treatment of failing arteriovenous fistulae (AVFs). MATERIALS AND METHODS Forty patients (26 men; mean age, 61 y ± 14.63) were randomized at 1:1 to undergo PCB (n = 20) or high-pressure balloon (HPB; n = 20) angioplasty of dysfunctional AVFs. There were no significant differences in baseline demographics between groups. Enrollment required a clinical diagnosis of a dysfunctional AVF attributed to a single stenotic lesion verified with digital subtraction angiography. Primary endpoints included device success, anatomic success, clinical success, and target lesion revascularization (TLR)-free survival. Secondary endpoints included dialysis circuit primary patency and procedure-related complication rates. RESULTS Device success rates were 100% in the HPB group and 35% in the PCB group (P < 0001): further dilation with an HPB was needed to achieve anatomic success in 13 of 20 cases in the PCB group (65%). Anatomic and clinical success rates were 100% in both groups. TLR-free survival (PCB, 308 d; HPB, 161 d; hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.236-0.966; P = .03) and access circuit primary patency (PCB, 270 d; HPB, 161 d; HR, 0.479; 95% CI, 0.237-0.968; P = .04) were significantly in favor of PCB angioplasty. No minor or major procedure-related complications occurred. CONCLUSIONS In this single-center study, the use of PCBs resulted in superior TLR-free survival and dialysis access circuit primary patency of dysfunctional AVFs. However, additional HPB postdilation was required in the majority of cases.

Safety and Efficacy of the StarClose Vascular Closure Device in More Than 1000 Consecutive Peripheral Angioplasty Procedures

Purpose To present a large singlecenter retrospective study investigating the safety and efficacy of the StarClose extravascular closure device in achieving hemostasis after antegrade or retrograde femoral artery catheterization during peripheral angioplasty procedures. Methods Between January 2004 and October 2009, 1213 StarClose devices were implanted in 850 consecutive patients (598 men; mean age 65.8±12.2 years) who underwent peripheral endovascular procedures. Femoral artery punctures included 625 (51.5%) retrograde and 588 (48.5%) antegrade accesses. The primary endpoints were hemostasis success, device failure, and major and minor complication rates up to 30 days. Results A 6-F vascular sheath was used in the majority of cases [39 (3.2%) 7-F and 9 (0.7%) 8-F]. The device was applied more than once in the same femoral artery of 124 (10.2%) limbs during different angioplasty sessions. Overall hemostasis success was achieved in 1139 (93.9%) cases. In 237 (20.8%) of those, additional manual compression for <5 minutes was necessary due to immediate vessel oozing. The remaining 74 (6.1%) cases required prolonged standard manual compression because of hemostasis failure, including 13 (1.1%) failures to deliver the clip. Overall major and minor complication rates were 0.3% (4/1213) and 5.3% (64/1213), respectively. Conclusion The StarClose vascular closure device is safe and effective in achieving hemostasis during antegrade and retrograde peripheral angioplasty procedures.

Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.

There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46–0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58–0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58–0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61–0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46–0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23–39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22–2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05–2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.