Paclitaxel-Coated Balloons: Review of a Promising Interventional Approach to Preventing Restenosis in Femoropopliteal Arteries.
ABSTRACT: Peripheral arterial disease (PAD), a major cause of morbidity and mortality worldwide, is characterized by intermittent claudication and is associated with chronic diseases such as diabetes and hypertension. The goal of treatment is to address the underlying cause and to modify risk factors. Although medical management is the first-line treatment of PAD, some individuals may have severe symptoms and require revascularization with percutaneous transluminal angioplasty with or without stent placement or surgery. Interventional approaches may, however, be associated with high prevalence of restenosis and subsequent complications such as critical limb ischemia and amputation. Drug-eluting balloons (DEBs) are a new interventional technology with the primary goal of preventing restenosis. We review the clinical trials and studies that assessed the efficacy and safety profile of DEB and will focus on the restenosis rate in femoropopliteal arteries including target lesion revascularization (TLR) and late lumen lesion (LLL) using different modalities of intervention such as stents and DEB. Average data collected from the trials reported included restenosis rate of 25%, 0.3?mm LLL, and 14% reduction in TLR with DEB versus uncoated balloons. Below the knee (BTK) only intervention studies were excluded from this review as endovascular approach is usually reserved for critical limb ischemia for BTK disease. Interventional approach to treat PAD with DEB appears to be a promising technology. Additional larger studies are needed to further define safety, efficacy, and longer term outcome with this novel technology.
Project description:Drug-eluting balloons (DEB) have significant value for treating coronary artery disease (CAD). However, the merits of using DEB versus drug-eluting stents (DES) to treat CAD remain controversial. Herein, we conducted a meta-analysis to compare the safety and efficacy of DEB and DES for treatment of CAD.We searched MEDLINE, EMBASE, and CENTRAL databases for eligible trials comparing DEB with DES for treatment of CAD. The primary endpoint was major adverse cardiac events (MACE); the secondary endpoints included in-lesion late lumen loss (LLL), binary restenosis (BR), myocardial infarction (MI), target lesion revascularization (TLR) and mortality.Twenty-three trials with a total of 2712 patients were included. There were no significant differences in the primary endpoint of MACE between the DEB and DES groups (Risk Ratio (RR) 1.19; 95% confidence interval (CI) (0.87, 1.63); P?=?0.27), or in the clinical outcomes of each of MACE's components, including TLR, MI and mortality. However, efficacy was significantly different between the DEB and DES groups, especially when we compared DEB to second-generation DES: in-lesion LLL (Mean Difference (MD) 0.11; (0.01, 0.22); P?=?0.03); binary restenosis (RR 1.46; (1.00, 2.13); P?=?0.05).DEB is equivalent to DES in terms of safety for managing CAD, and DEB may be considered as an alternative choice for treatment of CAD.
Project description:The role of drug-eluting balloons (DEB) is unclear. Increasing evidence has shown a benefit for the treatment of in-stent restenosis. Its effect on de novo coronary lesions is more controversial. Several smaller randomized trials found conflicting results.This is a systematic review and meta-analysis of randomized controlled trials (RCT) evaluating the effect of local Paclitaxel delivery/drug eluting balloons (DEB) (+/- bare metal stent) compared to current standard therapy (stenting) to treat de novo coronary lesions. Data sources for RCT were identified through a literature search from 2005 through 28 December 2012. The main endpoints of interest were target lesion revascularization (TLR), major adverse cardiac events (MACE), binary in-segment restenosis, stent thrombosis (ST), myocardial infarction (MI), late lumen loss (LLL) and mortality. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals.Eight studies (11 subgroups) and a total of 1,706 patients were included in this analysis. Follow-up duration ranged from 6 to 12 months. Overall, DEB showed similar results to the comparator treatment. The relative risk (RR) for MACE was 0.95 (0.64 to 1.39); P = 0.776, for mortality it was 0.79 (0.30 to 2.11), P = 0.644, for stent thrombosis it was 1.45 (0.42 to 5.01), P = 0.560, for MI it was 1.26 (0.49 to 3.21), P = 0.629, for TLR it was 1.09 (0.71 to 1.68); P = 0.700 and for binary in-stent restenosis it was 0.96 (0.48 to 1.93), P = 0.918. Compared to bare metal stents (BMS), DEB showed a lower LLL (- 0.26 mm (-0.51 to 0.01)) and a trend towards a lower MACE risk (RR 0.66 (0.43 to 1.02)).Overall, drug-eluting balloons (+/- bare metal stent) are not superior to current standard therapies (BMS or drug eluting stent (DES)) in treating de novo coronary lesions. However, the performance of DEB seems to lie in between DES and BMS with a trend towards superiority over BMS alone. Therefore, DEB may be considered in patients with contraindications for DES. The heterogeneity between the included studies is a limitation of this meta-analysis; different drug-eluting balloons have been used.
Project description:<h4>Background</h4>Drug-eluting balloon (DEB) has become an alternative option to drug-eluting stent (DES) for the treatment of in-stent restenosis (ISR). However, the effect of drug-eluting balloon with regular bare-mental stent (BMS) in de novo coronary artery disease (CAD) is unclear. This meta-analysis aimed to evaluate the efficacy of DEB with regular BMS compared to BMS or DES in de novo CAD.<h4>Methods</h4>Randomized controlled trials (RCTs) assessing the efficacy of DEB+BMS in comparison with BMS or DES were obtained by searching the PubMed, EMBASE, and Cochrane Library databases through January 2016. Primary endpoints were major adverse cardiac events (MACEs) and late lumen loss (LLL). Secondary endpoints included death, myocardial infarction (MI), target lesion revascularization (TLR), stent thrombosis (ST), binary restenosis, and minimum lumen diameter (MLD). Dichotomous and continuous data were presented as odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs), respectively, and analyzed using a random-effects model.<h4>Results</h4>A total of 14 RCTs involving 2281 patients were included in this meta-analysis. DEB+BMS showed significantly less MACEs (OR: 0.67, 95%CI 0.45 to 0.99, P = 0.04) and reduced LLL (MD: -0.30 mm, 95%CI: -0.48 mm to -0.11 mm, P = 0.001) compared with BMS. Meanwhile, treatment with DEB+BMS had disadvantages over DES in terms of MACEs (OR: 1.94, 95%CI 1.24 to 3.05, P = 0.004), LLL (MD: 0.20 mm, 95%CI: 0.07 mm to 0.33 mm, P = 0.003), TLR (OR: 2.53, 95% CI 1.36 to 4.72, P = 0.003), and MLD (MD: -0.25 mm, 95%CI: -0.42 mm to -0.09 mm, P = 0.003).<h4>Conclusions</h4>This limited evidence demonstrated that treatment with DEB+BMS appears to be effective in de novo CAD. In addition, DEB+ BMS clearly showed superiority to BMS, but is inferior to DES in the treatment of patients with de novo CAD. Hence, DES (especially new generation DES) should be recommended for patients with de novo CAD.
Project description:BACKGROUND:This quantitative meta-analysis was conducted to evaluate the efficacy and safety of drug-eluting balloon (DEB) vs. uncoated balloon (UCB) in patients with femoropopliteal arterial occlusive disease. METHODS:Electronic databases were searched to identify randomized controlled trials (RCTs) that compared DEB and UCB till November 2018. The random-effects model was used for conducting pooled analyses. RESULTS:Seventeen RCTs with 2706 patients were included in the final meta-analysis. Patients who received DEB had higher levels of minimal luminal diameter (MLD) at 6 (WMD: 0.77; 95%CI: 0.53 to 1.02; P?<?0.001) and 12?months (WMD: 1.33; 95%CI: 0.93 to 1.73; P?<?0.001) than those who received UCB. DEB reduced the late lumen loss (LLL) levels after 6 (WMD: -0.57; 95%CI: -?1.07 to -?0.06; P?=?0.029) and 12?months (WMD: -0.95; 95%CI: -?1.28 to -?0.62; P?<?0.001). DEB was found not superior over UCB on primary patency after 6?months (RR: 1.44; 95%CI: 0.88-2.35; P?=?0.149), whereas DEB increased the primary patency after 12 (RR: 1.51; 95%CI: 1.25-1.83; P?<?0.001) and 24?months (RR: 1.51; 95%CI: 1.30-1.77; P?<?0.001). Patients who received DEB had reduced the risk of restenosis after 6 (RR: 0.47; 95%CI: 0.33-0.67; P?<?0.001) and 12?months (RR: 0.55; 95%CI: 0.35-0.85; P?=?0.008). DEB reduced the risk of major adverse events after 6 (RR: 0.30; 95%CI: 0.14-0.61; P?=?0.001), 12 (RR: 0.49; 95%CI: 0.32-0.76; P?=?0.001) and 24?months (RR: 0.62; 95%CI: 0.41-0.92; P?=?0.018). CONCLUSIONS:DEB yielded additional benefits on MLD, LLL, primary patency, restenosis, TLR, and major adverse events than UCB in patients with femoropopliteal arterial occlusive disease.
Project description:PURPOSE:The post-hoc multivariable analysis of EffPac study data aimed to identify explanatory variables for efficacy of femoropopliteal artery angioplasty. METHODS:In the prospective, randomized, controlled EffPac study, patients were allocated to either DCB or plain old balloon angioplasty. Multivariable regression including interaction analysis was conducted to assess the impact of selected variables on the outcome measures of late lumen loss (LLL) at 6 months, and on binary restenosis, target lesion revascularization (TLR), clinical improvement, and hemodynamic improvement at 12 months. RESULTS:A total of 171 patients (69?±?8 years, 111 men) were treated at 11 German centers. Hypertension increased, and advanced age decreased LLL (B coefficient [B]: 0.7 [95% CI -?0.04 to 1.3], p?=?0.06 and -?0.3 per 10 years [95% CI -?0.5 to 0.01], p?=?0.06, respectively). DCB angioplasty decreased odds of 12-month TLR and binary restenosis (OR 0.4 [95% CI 0.2 to 0.8], p?=?0.01 and OR 0.1 [95% CI 0.01 to 0.6], p?=?0.02, respectively). Lesion length and severe calcification decreased clinical improvement (B: -?0.1 per 10 mm [95% CI -?0.1 to -?0.03], p?=?0.001 and -?0.1 [95% CI -?1.7 to -?0.1], p?=?0.03, respectively). DCB angioplasty in former smokers improved ABI (0.2 [95% CI 0.01 to 0.5], p?=?0.04). CONCLUSION:DCB angioplasty decreased the incidence of 12-month restenosis and TLR. Increasing lesion length and severe calcification reduced clinical improvement. Hypertension is suspected to facilitate, and advanced age to mitigate LLL. DCB improved ABI most in former smokers.
Project description:The femoropopliteal artery is one of the commonest sites of involvement in peripheral artery disease (PAD) leading to intermittent claudication and/or critical limb ischemia. Endovascular therapy for superficial femoral artery (SFA) disease has been recognized as a safe and efficient therapy and is recommended by current guidelines as the first-line approach. Although the widespread use of new-generation, self-expanding, nitinol stents in SFA stenosis has reduced the shortcomings associated with plain old balloon angioplasty (POBA), lumen renarrowing at the stented (in-stent restenosis - ISR) level still represents a relevant clinical problem, because of higher risk of recurrent ISR, occlusion and surgical revascularization compared to de-novo lesions. In this setting, different treatment options are available and drug-coated balloons (DCBs) have shown good results in terms of safety and effectiveness. In this review we examine the results of different trials exploring the outcome of using DCBs for the treatment of SFA ISR. The available data demonstrate that SFA ISR can be safely treated with percutaneous transluminal angioplasty with a DCB, with a reduction in recurrent restenosis and target lesion revascularization (TLR) at least at 1 year after POBA. The consistent and positive results of different registries and randomized trials support the use of DCB to reduce SFA ISR recurrence.
Project description:Symptomatic peripheral arterial disease management involves medical treatment and interventional procedures. Intermittent claudication and critical limb threatened ischemia (CLTI) should be individually considered with specific outcomes and procedures. When intervention is required, an endovascular approach is usually the first-line option. Plain balloon angioplasty was previously used to dilate clinically significant femoropopliteal lesions with variable results. However, over recent years, the use of self-expanding nitinol stents has enabled treatment of long lesions, yielding significantly improved clinical results. Drug-eluting technology has also exhibited a capacity to limit in-stent restenosis and to drive target revascularization. Nevertheless, calcifications and elastic recoil of the arterial wall remain risk factors for early restenosis and failure. Therefore, vessel preparation using specific devices is required to modify vessel compliance and debulk obstructive calcification. In this short review, we provide an overview of the options for gaining lumen before stenting or dilation using drug-coated balloons.
Project description:The aim of this investigator-initiated trial is to evaluate the safety and efficacy of the novel Luminor® paclitaxel-coated drug-eluting balloon (DEB) catheter (iVascular, S.L.U., Barcelona, Spain) in inhibiting restenosis and in ensuring long-term vascular patency.This is a multicenter randomized controlled trial to evaluate the Luminor® paclitaxel-coated DEB catheter for stenotic or occlusive lesions (length ?15 cm) in the superficial femoral artery (SFA) and the popliteal artery (PA) up to the P1 segment compared to the noncoated, plain old balloon angioplasty (POBA) catheter. In total 172 subjects will be treated with either the DEB catheter or the POBA catheter in 11 German study centers in a 1:1 randomization study design. The primary endpoint is late lumen loss (LLL) at 6 months. Secondary endpoints are patency rate, target lesion/vessel revascularization, quality of life (assessed with the Walking Impairment Questionnaire (WIQ) and the EQ-5D), change of Rutherford stage and ankle-brachial index, major and minor amputation rate at the index limb, number of dropouts and all-cause mortality.EffPac represents a randomized controlled trial that will provide evidence on the effectiveness of the Luminor® paclitaxel-coated DEB catheter for the reduction of restenosis compared to the POBA catheter for the SFA and the PA. The results of EffPac will allow direct comparison to other already-completed RCTs applying paclitaxel-coated DEBs from different manufacturers with different coating technologies in the same target vessel.ClinicalTrials.gov Identifier: NCT02540018 , registered on 17 August 2015. Protocol version: CIP Version Final04, 11 February 2016. EUDAMED No: CIV-15-03-013204.
Project description:A significant proportion of patients with severe lower limb peripheral arterial disease require revascularization. Over the past decade, an endovascular-first approach even for complex disease has gained widespread use among vascular specialists. An important limitation of percutaneous transluminal balloon angioplasty or stenting remains the occurrence of restenosis. Drug-coated balloons have emerged as an exciting technology developed to overcome the limitations of standard balloon angioplasty and stenting. Drug-eluting devices inhibit neointimal growth of vascular smooth muscle cells with the potential of preventing restenosis. This review provides a synopsis of the up-to-date evidence on the role of drug-coated balloons in the treatment of lower limb peripheral arterial disease. Bibliographic searches were conducted using MEDLINE, EMBASE, and the Cochrane Library electronic database. Eleven randomized clinical trials, two systematic reviews, and a published registry providing the best available evidence were identified. Current evidence suggests that angioplasty with drug-coated balloon is reliable, safe, and efficient in increasing patency rates and reducing target lesion revascularization and restenosis. However, it remains unknown whether these improved results can translate into beneficial clinical outcomes, as current randomized clinical trials have failed to demonstrate a significant benefit in limb salvage and mortality. Further randomized trials focusing on clinical and functional outcomes of drug-eluting balloons and on cost versus clinical benefit are required.
Project description:Background:Although drug-eluting stents (DES) have reduced the rates of in-stent restenosis (ISR) compared with bare-metal stents (BMS), DES related ISR (DES-ISR) still occurs and outcomes of DES-ISR remain unclear. The objective of this meta-analysis was to investigate the long-term clinical outcomes of patients with DES-ISR compared with patients with BMS related ISR (BMS-ISR) after the treatment of DES or drug-eluting balloon (DEB). Methods and results. We searched the literature in the main electronic databases including PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary endpoints were target lesion revascularization (TLR) and target vessel revascularization (TVR). The secondary endpoints included all cause death (ACD), cardiac death (CD), myocardial infarction (MI), stent thrombosis or re-in-stent restenosis (ST/RE-ISR), and major adverse cardiovascular events (MACEs). A total of 19 studies with 6256 participants were finally included in this meta-analysis. Results showed that the rates of TLR (P < 0.00001), TVR (P < 0.00001), CD (P=0.02), ST/RE-ISR (P < 0.00001), and MACEs (P < 0.00001) were significantly higher in the DES-ISR group than in the BMS-ISR group. No significant differences were found between the two groups in the rates of MI (P=0.05) and ACD (P=0.21). Conclusions:Our study demonstrated that patients with DES-ISR had worse clinical outcomes at the long-term follow-up than patients with BMS-ISR after the treatment of DES or DEB, suggesting that DES and DEB may be more effective for BMS-ISR than that for DES-ISR. Positive prevention of DES-ISR is indispensable and further studies concentrating on detecting the predictors of outcomes of DES-ISR are required.