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Paclitaxel-Releasing Balloon in Femoropopliteal Lesions Using a BTHC Excipient
Abstract
To evaluate the safety and efficacy of the novel Passeo-18 Lux paclitaxel-coated balloon compared with the Passeo-18 uncoated balloon in patients with symptomatic de novo or restenotic femoropopliteal lesions.
Sixty patients (34 men; mean age 70.7±10.1 years) in 5 European centers were enrolled in the BIOLUX P-I trial (ClinicalTrials.gov identifier NCT01056120) and randomized 1:1 to either the paclitaxel-coated balloon or the uncoated balloon. The primary endpoint was late lumen loss at 6 months. Secondary endpoints were binary restenosis at 6 months, clinically driven target lesion revascularization (TLR), change in ankle-brachial index and Rutherford classification, and major adverse events at 6 and 12 months.
At 6 months, patients treated with paclitaxel-coated balloons had a significantly lower late lumen loss (0.51±0.72 vs. 1.04±1.00 mm, p=0.033) and binary restenosis (11.5% vs. 34.6%, p=0.048) than the control group. Correspondingly, clinically driven TLR was lower in the paclitaxel-coated balloon group at 12 months [15.4% vs. 41.7% (p=0.064) for the intention-to-treat population and 16.0% vs. 52.9%, (p=0.020) for the as-treated population]. No death and one minor amputation were observed compared with two deaths and two minor amputations in the control group. No major amputations or thrombosis were reported.
The Passeo-18 Lux paclitaxel-coated balloon has been proven to be safe and effective in patients with femoropopliteal lesions, with superior performance outcomes compared with treatment with an uncoated balloon.
© The Author(s) 2015.
... Of the 34 studies deemed eligible for quantitative synthesis, 30 studies were multicenter RCTs 18,26-54 ; the remaining 4 were single-center trials [55][56][57][58] (Table 1). Twenty-five studies [26][27][28][29][30][31]33,[35][36][37]39,40,[43][44][45][46]48,50,51,53-58 employed a 1:1 randomization process and conducted an intention to treat analysis, and 2 studies 42,52 compared a paclitaxel device to 2 nonpaclitaxel intervention groups implementing 1:1:1 randomization process. A further 6 studies 18,32,38,41,47,49 employed a 2:1 randomization process, and a single study 34 employed a 3:1 randomization process, paclitaxel to control. ...
... Twenty-seven studies 18,26,27,[29][30][31]34,[36][37][38][39][40][41][44][45][46][47][48][49][50][51][52][53][54][55]57,58 used paclitaxel-coated balloons. One study used a suboptimal design intentionally combining paclitaxel-coated balloons and stents, 43 and the remaining 6 studies 28,32,33,35,42,56 used paclitaxel eluting stents (Table 1). ...
... The properties of these devices are given in Table 3 43 All other devices delivered a paclitaxel dose of 2 or 3 μg/mm 2 . 18,26,[28][29][30][31][32][33][34][35][36]38,39,41,42,[44][45][46][47][48][49][50][51][52][53][54][56][57][58] Of the 27 DCB studies, 23 involved the sole application of paclitaxel-coated DCB (23 vs PTA and 1 vs BMS), 26,27,[29][30][31]34,37,[39][40][41]46,49,[51][52][53][54][55]57 4 combined DCB with BMS (vs PTA and BMS). 36,44,50,58 Of the 6 DES studies, 2 compared DES with surgical bypass with prosthetic conduit, 32,33 1 compared DES with PTA, 35 2 compared DES with BMS, 28,56 and a single study compared DES with BMS with and without cilostazol. ...
Purpose:
A late increased mortality risk has been reported in a summary level meta-analysis of patients with femoropopliteal artery occlusive disease treated with paclitaxel-coated angioplasty balloons and stents. However, at the longer follow up timepoints that analysis was limited by small trial numbers and few participants. The aim of this study was to report an updated summary level risk of all-cause mortality after treatment with paclitaxel-coated devices in that same patient group.
Materials and methods:
We performed a systematic review and meta-analysis of randomized controlled trials to investigate the mortality outcomes associated with paclitaxel-coated devices used to treat patients with occlusive disease of femoropopliteal arteries (last search date December 10, 2020). The single primary endpoint was all-cause mortality.
Results:
We identified 34 randomized controlled trials (7654 patients; 84% intermittent claudication). There were 622 deaths among 4147 (15.0%) subjects in the paclitaxel device group and 475 deaths among 3507 (13.5%) subjects in the noncoated control group [relative risk ratio (RR) 1.07, 95% confidence interval (CI) 0.96 to 1.20, p=0.20, I2=0%). All-cause mortality was similar between groups at 12 months (34 studies, 7654 patients; RR 0.99, 95% CI 0.81 to 1.22, p=0.94, I2=0%), 24 months (20 studies, 3799 patients; RR 1.16, 95% CI 0.87 to 1.55, p=0.31, I2=0%), and 60 months (9 studies, 2288 patients; RR 1.19, 95% CI 0.98 to 1.45, p=0.08, I2=0%).
Conclusion:
This updated meta-analysis with included additional trials and larger patient numbers shows no evidence of increased risk of all-cause mortality in patients treated with paclitaxel-coated devices, compared with uncoated devices for femoropopliteal disease at all time points to 60 months. There is therefore no justification to limit their use, or alter regulatory body follow-up recommendations in this patient population.
Systematic review registration:
CRD42020216140.
... Following numerous randomized controlled trials (RCT) showing superior outcomes for drug-coated balloon (DCB) over uncoated balloons [2][3][4][5][6][7], DCB is broadly used as a first-line therapy in femoropopliteal lesions [8]. For the treatment of below-the-knee artery lesions, the outcomes have been controversial so far [9,10]. ...
... The aim of the BIOLUX P-III all-comers single-arm study was to strengthen Passeo-18 lx promising efficacy and safety outcomes shown in BIOLUX P-I and BIOLUX P-II first-in-human RCTs [2,9] in a large real-world patient population with long-term safety data. Twelve-month results of the first 700 patients, namely the all-comers cohort, have been published [11]. ...
... The Passeo-18 lx DCB (BIOTRONIK AG, Switzerland), CE marked since 2014, has been previously described [2,9]. In brief, it is a balloon that is coated with 3 lg paclitaxel per mm 2 incorporated in the excipient Butyryltri-hexyl-citrate (BTHC). ...
Purpose:
After promising small randomized trials, the aim of BIOLUX P-III was to further investigate the safety and performance of the Passeo-18 lx drug-coated balloon in infrainguinal arteries under real-world conditions.
Methods:
BIOLUX P-III is a global prospective single-arm study with follow-up at 6, 12 and 24 months. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months. The primary performance endpoint was freedom from clinically driven target lesion revascularization (TLR) within 12 months.
Results:
877 patients/1084 lesions were enrolled. Diabetes mellitus was present in 47.7%, and 42.1% had critical limb ischemia (CLI). The mean lesion length was 89.0 mm with 76.1% of calcified lesions, and 24.9% occluded. At 24 months, freedom from MAE was 83.1% in the full cohort; 84.9% in the femoropopliteal population (592 patients, 691 lesions); 77.7% for long lesions (187 subjects/192 lesions); and 72.5% in the in-stent restenosis (ISR) subgroup (103 subjects/116 lesions). Twenty-four-month freedom from clinically driven TLR was 88.1% in the full cohort; 88.9% in the femoropopliteal population; 80.3% for the long lesions; and 78.4% for ISR. Twenty-four-month all-cause mortality was 12.0% in the full cohort, 10.2% in the femoropopliteal population, 14.8% for the long lesions and 12.0% for ISR. There was no device- or procedure-related death up to 24-month follow-up.
Conclusion:
The BIOLUX P-III 24-month outcomes confirm the safety and performance of Passeo-18 lx in infrainguinal arteries in a large population treated under real-world conditions with low complication rates and good clinical outcomes (NCT02276313).
... These antiproliferative drugs are delivered to the vessel wall during balloon inflation, inhibiting neointimal hyperplasia of the vessel wall [8,9]. Several randomized controlled trials (RCTs) have previously demonstrated that DCBs provide better outcomes than plain balloons in femoropopliteal arteries [10][11][12][13][14][15][16][17]. However, previous studies comparing DCB and plain balloon angioplasty for belowthe-knee (BTK) artery disease have reported mixed results, requiring further investigation to establish the role of DCB in the treatment of BTK artery disease [18][19][20]. ...
... The Passeo-18 Lux (Biotronik AG, Buelach, Switzerland) is a DCB made by coating paclitaxel 3 μg/mm 2 on the surface of the Passeo-18 plain balloon catheter (Biotronik AG) using butyryl-tri-n-hexyl citrate (BTHC) as an excipient. Compared with the uncoated Passeo-18 balloon, the Passeo-18 Lux DCB showed superior outcomes for femoropopliteal lesions in the BIOLUX P-I RCT [10], and comparable outcomes for infrapopliteal lesions in the BIOLUX P-II RCT [21]. In addition, the BIOLUX P-III study, a single-arm, prospective, international, multicenter, post-market study operating an all-comers registry, reported 24-month outcomes of Passeo-18 Lux DCB in a large population in real-world clinical practice [22]. ...
Objective:
To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries.
Materials and methods:
Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2-5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) within 12 months after the procedure.
Results:
A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56-133 mm). Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively.
Conclusion:
The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.
... These balloons are coated with an antiproliferative drug, paclitaxel; and have documented effects on reducing the rate of restenosis when treatments are performed in other vascular territories. [16][17][18][19][20][21][22][23][24][25][26] Two randomized clinical trials, 27,28 as well as many smaller series, have been published on this topic reporting conflicting results. Whereas treatment is considered safe, 27,50,51 some studies have shown positive effects on primary patency and reduced number of reinterventions, 27,31,33,[35][36][37]39,40,45,47,52 whereas others have not. ...
... For example, there is a considerable amount of scientific evidence supporting a possible antirestenotic effect in various vascular territories. [16][17][18][19][20][21][22][23][24][25][26]28,30,31,33,[35][36][37][38][39][40][41][42][43][44][45][46][47]49,56 However, these procedures have not been fully adopted as standard care and safety issues have been discussed in recent years. 57 In particular, a meta-analysis from 2018 suggested an increase in late mortality in the cohort receiving drug-eluting therapy, so the use of this technology was heavily questioned. ...
Objective
To compare the efficacy of angioplasty using drug-eluting balloons (DEB) compared with plain old balloon angioplasty (POBA) to reduce the rate of restenosis.
Methods
This prospective, single-centre, single-blinded, 1:1 randomized, clinical trial enrolled patients that had primary or restenotic lesions in native upper extremity arteriovenous (AV) fistulas or at the graft-venous anastomosis. Patients were randomized to angioplasty with a POBA or a DEB. The primary effectiveness endpoints were freedom from target lesion revascularization (TLR) and functional status of access circuit at 12 months.
Results
A total of 42 (28 male, 14 female; age range, 42–83 years) patients were enrolled. Patients were followed for 12 months. No significant differences were detected between the POBA and DEB groups regarding total number of TLR procedures (31 versus 36, respectively), freedom from TLR (3 versus 4, respectively) and functional status of the access circuit at 12 months (14 of 20 patients [70%] versus 17 of 22 patients [77%], respectively).
Conclusion
This clinical trial did not demonstrate any significant differences between DEB angioplasty and standard balloon angioplasty when treating dysfunctional haemodialysis access.
... The THUNDER trial findings were supported by the PACIFIER [24], LEVANT-II [25], BIOLUX P-I [26], AcoArt-I [27], IN.PACT [20], and ILLUMENATE trials [22]. ...
... In particular, paclitaxel drug-coated balloon (DCB) catheters are desirable candidates for the treatment of femoropopliteal arteries with the potential to reduce restenosis without leaving a stent behind. Multiple randomized controlled trials (RCTs) have demonstrated the safety and effectiveness of DCBs for the treatment of symptomatic femoropopliteal arterial disease compared to plain balloon angioplasty [3][4][5][6][7][8][9][10][11]. Single-arm prospective global studies further evaluated DCBs for real-world patients with longer, more complex lesions [12][13][14][15][16]. ...
Purpose:
To summarize the 5-year outcomes of drug-coated balloon (DCB) for the treatment of femoropopliteal lesions in patients with diabetes mellitus (DM) or chronic limb-threatening ischemia (CLTI) compared to non-DM and intermittent claudication (IC).
Methods:
The IN.PACT Global study was a real-world prospective, multicenter, international, single-arm study that enrolled 1535 participants. Post hoc analyses were conducted for participants with DM (n = 560) versus non-DM (n = 842) and CLTI (n = 156) versus IC (n = 1246). Assessments included freedom from clinically driven target lesion revascularization (CD-TLR) through 60 months, a composite safety outcome (freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and freedom from CD-target vessel revascularization within 60 months), and major adverse events (MAEs).
Results:
Kaplan-Meier estimates of 60-month freedom from CD-TLR were 67.7% and 70.5% (p = 0.25) in the DM and non-DM cohorts; and 60.7% and 70.5% (p = 0.006) in the CLTI and IC cohorts. The Kaplan-Meier 60-month composite safety outcomes were 65.1% DM versus 68.9% non-DM (p = 0.12); 53.2% CLTI versus 69.1% IC (p < 0.001). Between DM and non-DM, MAE rates were not significantly different through 60 months except for all-cause mortality which was higher in DM (23.8% versus 16.6%; p < 0.001). Participants with CLTI had a higher cumulative incidence of major target limb amputation (6.8% versus 1.1%; p < 0.001) and all-cause mortality (37.4% versus 17.4%; p < 0.001) through 60 months compared to IC.
Conclusions:
In this real-world study, 5-year reintervention rates following DCB angioplasty were similar between DM and non-DM, but mortality rates were expectedly higher in patients with DM. Reintervention, mortality, and amputation rates were all higher in CLTI patients compared to IC, which is consistent with the known frailty of this patient population.
Level of evidence:
Level 3, Non-randomized controlled cohort/follow-up study.
... The role of drug-coated balloons (DCBs), such as the Passeo-18 Lux DCB (Biotronik, Berlin, Germany), has previously been outlined in trials such as the BIOLUX P-I and P-II [5][6][7]. Still, despite demonstrating superiority in treating symptomatic femoropopliteal lesions, there remains a concern regarding their effect in females [3]. ...
Purpose
To evaluate the use of drug-coated balloons in a real-world patient population with peripheral arterial disease and analyse the impact of sex on mid-term outcomes following their utilisation.
Methods
The BIOLUX P-III is a prospective, international, multi-centre, registry of patients with infra-inguinal lesions treated using the Passeo-18 Lux, a drug-coated balloon. Our study is a 24-month subgroup analysis of these patients; primary endpoints were freedom from major adverse events and clinically driven target lesion re-vascularisation within 12 months post-intervention.
Results
Of the 877 patients in the registry, 561 (64.0%) were male and 316 (36.0%) were female. Chronic limb threatening ischaemia (Rutherford class ≥ 4) occurred in 35.7% of males and 40.6% of females. Rates of freedom from major adverse events and clinically driven target lesion re-vascularisation at 12 months were 87.3% (95% confidence interval [CI] 84.2–89.9) and 90.4% (95% CI 86.5–93.3), and 92.3% (95% CI 89.9–94.1) and 92.9% (95% CI 89.7–95.1) in males and females, respectively. All-cause mortality at 24 months was 12.0% (95% CI 9.4–15.3) in males and 11.9% (95% CI 8.6–16.5) in females. The major target limb amputation rate at 24 months was 9.1% (95% CI 6.9–11.9) in males and 4.0% (95% CI 2.3–7.0) in females.
Conclusion
Treatment with the Passeo-18 Lux DCB demonstrated high efficacy and low complication rates. Despite the greater proportion of chronic limb threatening ischaemia observed in females, males were at a greater risk of ipsilateral major limb amputation and major adverse events following drug-coated balloon utilisation.
Clinical Trial Registration
NCT02276313.
Level of Evidence
Level 4.
... Fifteen RCTs were included with a total of 2,825 patients and a median-weighted follow-up of 1.73 years ( Figure 1). [10,12,13,14,15,16,17,18,19,20,21,22,23,24,25,27,28]. The characteristics of the included studies, patients, lesions, and procedures are described in Tables 1, 2 ...
... These trials included the Chinese study (AcoArt-I) and major other multicenter trials from Europe. 16,[18][19][20][21][22][23][24][25][26][27] However, these trials showed conflicting results in terms of the need for TLR between the two procedures. The risk of TLR was similar in the LEVANT I trial at 6, 12, and 24 months, while DCB was favored due to lower TLR at 2-year follow-up of the CONSEQUENT cohort; this trial also demonstrated the cost-effectiveness of the DCB angioplasty attributed to the reduction of the rate of TLR. ...
Background:
The relative merits of the drug-coated balloon (DCB) versus uncoated balloon (UCB) angioplasty in endovascular intervention for patients with symptomatic lower extremity peripheral arterial disease (PAD) remains controversial.
Methods:
Online databases were queried with various combinations of keywords to identify relevant articles. Net adverse events (NAEs) and its components were compared using a random effect model to calculate unadjusted odds ratios (ORs).
Results:
A total of 26 studies comprising 26,845 patients (UCB: 17,770 and DCB: 9075) were included. On pooled analysis, DCB was associated with significantly lower odds of NAE (OR: 0.47, 95% confidence interval [CI]: 0.36-0.61), vessel restenosis (OR: 0.46, 95% CI: 0.37-0.57), major amputation (OR: 0.68, 95% CI: 0.47-99), need for repeat target lesion (OR: 0.38, 95% CI: 0.31-0.47) and target vessel revascularization (OR: 0.62, 95% CI: 0.47-0.81) compared with UCB. Similarly, the primary patency rate was significantly higher in patients undergoing DCB angioplasty (OR: 1.44, 95% CI: 1.19-1.75), while the odds for all-cause mortality (OR: 0.96, 95% CI: 0.85-1.09) were not significantly different between the two groups. A subgroup analysis based on follow-up duration (6 months vs. 1 vs. 2 years) followed the findings of the pooled analysis with few exceptions.
Conclusions:
The use of DCB in lower extremity PAD intervention is associated with higher primary patency, lower restenosis, lower amputation rate, and decreased need for repeat revascularization with similar all-cause mortality as compared to UCB.
... 12 In terms of biologic therapy for peripheral vasculature, paclitaxel-based therapies for femoropopliteal indications is arguably the largest and strongest body of evidence on device performance ever produced for any peripheral endovascular therapy. 10,11,[17][18][19] This contrasts with the coronary vasculature, in which cardiologists perceive limus to be superior to paclitaxel because of lower restenosis rates in the coronary bed following sirolimus-eluting versus paclitaxel-eluting stents. 20 Sirolimus is a potent antiproliferative agent that prevents activation of smooth muscle cells after vascular injury. ...
Introduction
Sirolimus coated balloon (SCB) is a promising treatment option to prevent restenosis for peripheral arterial occlusive disease (PAOD). This is a pilot first-in-human study of MagicTouch percutaneous transluminal angioplasty (PTA) SCB for treatment of PAOD for both femoropopliteal and below the knee arteries (BTK).
Material and Methods
Xtreme Touch-Neo [MagicTouch PTA] Sirolimus Coated Balloon (XTOSI) pilot study is a prospective, single-arm, open-label, single-center trial evaluating MagicTouch PTA SCB for symptomatic PAOD. Primary endpoint was defined as primary patency at 6 months (duplex ultrasound peak systolic velocity ratio ≤2.4). Secondary endpoints included clinically driven target lesion revascularization (CD-TLR), amputation free survival (AFS), all-cause mortality, and limb salvage success.
Results
Fifty patients were recruited. The mean age was 67 (n=31 [62%] males). SCB was applied to femoropopliteal in 20 patients (40%) and BTK in 30 patients (60%). Majority of treatments (94%) were performed for limb salvage indications (Rutherford scores 5 or 6). This was a high risk cohort, in which 90% had diabetes, 36% had coronary artery disease, 20% had end stage renal failure, and American Society of Anaesthesiologists (ASA) score was 3 or more in 80%. Mean lesion length treated was 227±81 mm, of which 36% were total occlusions. Technical and device success were both 100%. At 30 days, mortality was 2% and major limb amputation was also 2%. Six-month primary patency was 80% (88.2% for femoropopliteal; 74% for BTK). At 12 months, freedom from CD-TLR was 89.7% (94.1% for femoropopliteal; 86.3% for BTK), AFS was 81.6% (90.0% for femoropopliteal; 75.9% for BTK), all-cause mortality was 14.3% (10.0% for femoropopliteal; 17.2% for BTK), and limb salvage success was 92.9% (94.4% for femoropopliteal; 91.7% for BTK). There was a statistically significant increase between baseline and 6-month toe pressures for both femoropopliteal (57.3±23.3 mm Hg vs 82.5±37.8 mm Hg; p<.001) and BTK lesions (52.8±19.2 mm Hg vs 70.7±37 mm Hg; p<.037). At 12 months, wound healing rate was 33/39 (84.6%).
Conclusions
MagicTouch PTA SCB in the XTOSI study showed promising 6-month primary patency and encouraging 12-month freedom from CD-TLR, AFS, and limb salvage rates. No early safety concerns were raised. Randomized trials are needed to investigate the safety and efficacy of SCB for treatment of PAOD.
... [4] Drug-coated balloon (DCB) use has shown promising results in reducing restenosis of coronary stents, [5,6] although there is no standard treatment for ISR in the femoropopliteal artery. [7] Several recent randomized studies have evaluated the safety and efficacy of DCBs among patients with ISR in the femoropopliteal artery, [8][9][10] although the findings have been inconsistent. Thus, there is no consensus regarding the ideal strategy for treating ISR in the femoropopliteal artery, and we performed a meta-analysis to compare the outcomes of DCB use and balloon angioplasty (BA) in this setting. ...
Background:
The introduction of endovascular surgery has led to frequent stent use, although in-stent restenosis (ISR) remains a challenging issue. Drug-coated balloon (DCB) and conventional balloon angioplasty (BA) are common endovascular procedures for addressing ISR in the femoropopliteal artery. However, there is controversy regarding which procedure provides the greatest benefit to patients.
Methods:
The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for prospective controlled trials that compared DCB and BA for patients with ISR in the femoropopliteal artery. The study has been approved by Ethics Committee of Wuhan Central Hospital.
Results:
The meta-analysis included 6 prospective trials with 541 patients. We found that DCB use was associated with significant reductions in binary restenosis at 6 months (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.33-0.63; P < .00001), binary restenosis at 1 year (RR: 0.44, 95% CI: 0.34-0.57; P < .00001), target lesion revascularization (TLR) at 6 months (RR: 0.36, 95% CI: 0.20-0.65; P = .0006), and TLR at 1 year (RR: 0.38, 95% CI: 0.27-0.54; P < .00001). The DCB group also had significantly better clinical improvement (RR: 1.39, 95% CI: 1.13-1.71; P = .002), although we did not detect inter-group differences in terms of death, target vessel thrombosis, or ipsilateral amputation. The brand of DCB may a cause of heterogeneity.
Conclusion:
Relative to BA, DCB use increases the durability of treatment for ISR in the femoropopliteal artery, based on significant reductions in binary restenosis and TLR at 6-12 months after the procedure. Furthermore, DCB use was associated with better clinical improvement. However, additional randomized controlled trials are needed to validate these findings.
... Superiority of Passeo-18 lx DCB over standard balloon angioplasty (POBA) regarding the primary endpoint of 6-month late lumen loss and the secondary endpoint of 6-month binary restenosis had been demonstrated earlier by the BIOLUX P-I randomized controlled trial (RCT). However, the small-scale study had not been powered to compare clinical endpoints, and thus, difference in the incidence of clinically driven target lesion revascularization (TLR) between groups did not reach statistical significance (DCB 15.4% vs. POBA 41.7%, p = 0.06) [2]. The BIOLUX P-II RCT on below-the-knee (BTK) lesions showed similar clinical outcomes after DCB angioplasty and POBA. ...
... The Passeo-18 Lux DCB (Biotronik AG) has been previously described. 13,14 The balloon is coated with 3 µg paclitaxel per mm 2 incorporated in the excipient butyryl-trin-hexyl citrate (BTHC). The balloon is available in diameters of 2.0 to 7.0 mm and lengths of 40 to 120 mm; balloons with diameters up to 4.0 mm are 4-F compatible and those with diameters from 5.0 to 7.0 mm are 5-F compatible. ...
Purpose
To report the outcomes after treating stenotic or occluded femoropopliteal lesions with a drug-coated balloon (DCB) followed by the implantation of a thin-strut self-expanding bare metal stent in the BIOLUX 4EVER trial ( ClinicalTrials.gov identifier NCT02211664).
Materials and Methods
The prospective, multicenter, physician-initiated BIOLUX 4-EVER trial was conducted at 5 centers in Belgium and enrolled 120 patients (mean age 70.9±10.5 years; 79 men) with symptomatic stenotic or occluded de novo femoropopliteal lesions. A fifth of the patients had diabetes mellitus and nearly half had previous peripheral artery interventions. The lesions were a mean 83.3±49.5 mm long with a mean reference vessel diameter of 5.26±0.59 mm. Lesions were treated with a Passeo-18 Lux DCB followed by the implantation of a Pulsar-18 bare metal stent. Follow-up visits were conducted at 1, 6, 12, and 24 months postprocedure; the main outcome was primary patency at 12 months.
Results
Technical success was obtained in all patients. Primary patency was observed in 89.9% of patients (95% CI 84.0% to 95.8%) at 12 months and in 83.5% at 24 months (95% CI 89.9% to 97.3%), and freedom from target lesion revascularization was 93.6% (95% CI 89.9% to 97.3%) and 86.1% (95% CI 79.9% to 92.3%), respectively. Ten patients died throughout the course of the trial (90.7% survival at 24 months), all of noncardiovascular causes. The ankle-brachial index improved from 0.68±0.09 at baseline to 0.93±0.11 and 0.93±0.12 at 12- and 24-month follow-up visits (p<0.001). An improvement of at least 1 Rutherford category was observed in 91 of 94 patients (96.8%) at 12 months and 78 of 83 patients (93.4%) at 24 months (p<0.001).
Conclusion
The combination of a Passeo-18 Lux DCB followed by a Pulsar-18 stent implantation produced safe and effective outcomes in the treatment of femoropopliteal lesions at up to 24 months. Adding paclitaxel to the bare nitinol stent platform by predilating with a Passeo-18 Lux DCB seems to increase efficacy at 1 and 2 years compared with the use of bare metal stents only, which were investigated in the precursor 4-EVER study.
... Of these, 18 studies were excluded due to the following reasons: other interventions (n = 9), trials reporting the same populations (n = 7), and patients with other PAD (n = 2). Finally, 17 RCTs were considered eligible for final meta-analysis [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Review of the reference lists of these studies yielded no new eligible study. ...
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.
... Sample size in several included studies was smaller than 50 patients in each arm studied, which greatly reduces their statistical power and it cannot be completely corrected by using random-effects analysis. [3][4][5][6] The readers are then exposed to a plethora of comparisons and Forrest plots that show apple-to-oranges comparisons due to heterogeneous studies included, such as some that describe first and others that describe third-generation atherectomy devices. In addition, control groups from each included study in a NMA are used as "anchors", in this case plain balloon angioplasty, for the indirect comparisons among different intervention arms. ...
... Drug-coated balloons (DCBs) were developed to overcome these limitations. Many randomized controlled trials(RCTs) [2][3][4][5][6] have shown consistent superior outcomes of DCBs over uncoated balloons in femoropopliteal lesions, with data up to 5 years for some studies [7][8][9][10]. But,their application in lower limbs is still insu cient. ...
Background: At present, there are many clinical trials of drug coated balloon in the treatment of lower extremity arterial occlusive diseases, but there are not many clinical data in the real world study. Here we aimed to evaluate the efficacy and safety ofAcotec drug-coated balloon (DCB) for chronic ischemic disease in lower extremity.
Methods: Clinical data of 435 patientswith 564occlusive/stenotic lesions in 492lower extremities treated by DCB from April 2016 toApril2019 were retrospectively analyzed.The mean age was 63years.Rutherford stage 2, 3, 4, 5, and 6 were classified in 11, 167, 182, 109, and 23 limbs, respectively.The mean length of the targeted lesions was 179.6mm. Of all the lesions, 436 located at femoraland/or popliteal arteries, and 128 at infra-popliteal arteries. All the patients were followed up at 6-month intervals. The major evaluation endpoints included late lumen loss (LLL), target lesion restenosis, target lesion revascularization (TLR), and severe clinical events including mortality and major amputation.
Results: The technique success rate was 96.1%.Stents were placed in 57 (13.1%) cases for flow-limited dissections or remnant stenosisgreater than 50% after DCB angioplasty.The mean follow-up time was 28.5 ± 12.1 months (12-48 months). The meanLLLwas 1.1 mm, 1.8mm, and 2.8 mm, respectively, 1, 2, and 3 years after operation. The rate ofrestenosis and TLRwas 17.3%and8.2%, respectively, 1 year after operation; 20.6% and 11.6%, respectively, 2 years after operation; 29.4% and 18.3%, respectively, 3 years after operation.Fourteenpatientsdiedand 25received amputation.
Conclusion: AcotecDCBwas safe and effective in treating chronic ischemic diseases of lower extremities.A better clinical outcome was achieved in femoro-popliteal arteries, compared toinfrapopliteal arteries.
... 12 Numerous randomized controlled trials (RCTs) have demonstrated a clear benefit of DCBs over uncoated balloon angioplasty in terms of improved patency and reduced reintervention and bailout stent rates. 3,4,11,[13][14][15][16][17][18] Additionally, paclitaxel-based modalities seem to provide important economic benefits compared to their non-antiproliferative counterparts. 19,20 Thus, DCBs have become the treatment of choice for both de novo and restenotic TransAtlantic Inter-Society Consensus II (TASC) A and B femoropopliteal lesions and represent a viable alternative to scaffolds for complex disease. ...
Purpose: To report the 36-month outcomes from the prospective, multicenter, single-arm IN.PACT Global Study ( ClinicalTrials.gov identifier NCT01609296) evaluating the performance of the IN.PACT Admiral drug-coated balloon (DCB) in real-world patients with femoropopliteal occlusive disease. Materials and Methods: The IN.PACT Global Study was conducted at 64 international sites and enrolled 1535 patients with complex lesions, which included bilateral disease, multiple lesions, de novo in-stent restenosis, long lesions, and chronic total occlusions. The predefined full clinical cohort included 1406 patients (mean age 68.6 years; 67.8% men) with claudication or rest pain treated with the study DCB. Mean lesion length was 12.09±9.54 cm; 18.0% had in-stent restenosis, 35.5% were totally occluded, and 68.7% were calcified. Freedom from clinically-driven target lesion revascularization (CD-TLR) was evaluated through 36 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from major target limb amputation and clinically-driven target vessel revascularization within 36 months. All safety and revascularization events were reviewed by an independent clinical events committee. Results: The Kaplan-Meier estimate of freedom from CD-TLR through 36 months was 76.9%. The composite safety endpoint was achieved in 75.6% of patients. The 36-month all-cause mortality rate was 11.6%, and the major target limb amputation rate was 1.0%. The Kaplan-Meier estimate of freedom from CD-TLR through 36 months was significantly lower in patients with chronic limb-threatening ischemia (CLTI) compared with claudicants (67.6% vs 78.0%; p=0.003). Lesions affecting both the superficial femoral artery (SFA) and popliteal artery had lower Kaplan-Meier freedom from CD-TLR through 36 months (69.2%) than either isolated SFA (79.7%) or popliteal artery lesions (76.5%; log- rank p<0.001). Predictors of CD-TLR through 36 months included increased lesion length, reference vessel diameter ≤4.5 mm, in-stent restenosis, bilateral disease, CLTI, and hyperlipidemia. Conclusion: DCB angioplasty with the IN.PACT Admiral DCB for femoropopliteal disease in a diverse and complex real-world population is associated with sustained clinical efficacy and low rates of reinterventions at 3 years after the initial procedure.
Purpose:
The Passeo-18 Lux DCB long lesion cohort analysis was designed to further investigate the clinical performance and safety of Passeo-18 Lux DCB in complex femoropopliteal TASC C and D lesions in an all-comers patient population.
Material and methods:
Data from the BIOLUX P-III SPAIN, a prospective, national, multi-center, post-market all-comers registry conducted from 2017 to 2019, and a matching long lesion subgroup from the BIOLUX P-III global all-comers registry conducted from 2014 to 2018, were pooled for analysis. The primary safety endpoint is freedom from major adverse events (MAE) at 6 months and the primary performance endpoint is fCD-TLR at 12 months both adjudicated by an independent Clinical Events Committee.
Results:
A total of 159 patients of which 32.7% had critical limb ischemia were included in the Passeo-18 Lux long lesion cohort. Mean lesion length was 248.5 mm ± 71.6 mm and the majority were occluded (54.1%), calcified (87.4%) and were of type TASC C (49.1%) and type TASC D (50.9%). Freedom from MAEs was 90.6% [95% CI 84.6, 94.3] at 6 months and 83.9% [95% CI 76.7, 89.0] at 12 months. fCD-TLR was 84.4% [95% CI 77.3, 89.5] at 12 months. Freedom from target limb major amputation was 98.6% [95% CI 94.6, 99.7] and all-cause mortality was 5.3% [95% CI 2.7, 10.4] at 12 months. There were no device- or procedure-related death or amputation up to 12-month follow-up.
Conclusion:
Passeo-18 Lux DCB is safe and effective for the treatment of long femoropopliteal lesions in a real-word setting.
Paclitaxel drug-coated balloons (DCBs) have been shown to improve patency and lower revascularization rates compared with plain old balloon angioplasty. DCBs continue to evolve by improving balloon coating techniques that minimize the quantity of particles washed off into the bloodstream while maximizing drug retention and vascular-healing profile. Against this backdrop, it is clear that the future of antiproliferatives for the superficial femoral artery will focus on enhancements in device coating materials that will improve the efficiency of drug delivery. The Ranger DCB system recently gained US FDA approval for use. This review discusses the background of DCBs and how the Ranger DCB builds on these previous platforms based on experimental and clinical data.
Objectives:
Paclitaxel-coated balloon angioplasty has been established as the first-line therapy of femoropopliteal artery disease. The primary objectives of the study were to evaluate the performance and the safety of the GORE-DCB Catheter in the treatment of atherosclerotic femoropopliteal lesions of patients with peripheral artery disease for CE-Mark approval.
Methods:
Prospective, single-arm, multicenter study with 24 months follow-up. The GORE-DCB Catheter consists of a drug-coated nylon (inner layer)/ePTFE (outer layer) composite balloon. The ePTFE layer is coated with paclitaxel (concentration: 3.5μg/mm2), and the excipients stearic acid/tromethamine (tris). The primary endpoints were 6-month late lumen loss (LLL) and 30-day of freedom from Major Adverse Events (MAE).
Results:
Fifty-two subjects were enrolled, 69% men, median age 69 (49-83) years. Acute device success was 100%, the 30-day MAE rate was zero. Study primary endpoint of LLL (-0.17 mm) showed significant superiority compared to the performance goal of uncoated PTA balloon catheters from literature. At 1 and 2 years primary patency rates were 81.8% and 68.7%, respectively, and freedom from clinical driven target lesion revascularization rates were 87.9% and 83.4%, respectively.
Conclusion:
The study demonstrates that the treatment of lesions in femoropopliteal arteries with the GORE-DCB Catheter is safe and effective.
Background:
Long-term data on drug-coated balloon (DCB) outcomes in complex femoropopliteal atherosclerotic lesions are limited.
Objectives:
The authors sought to report 5-year safety and effectiveness outcomes of a paclitaxel DCB for the treatment of de novo in-stent restenosis (ISR), long lesions (LL), or chronic total occlusions (CTOs) in the prespecified imaging cohorts of the IN.PACT Global Study.
Methods:
The IN.PACT Global study was a prospective, international single-arm study. Assessments through 5 years included freedom from clinically driven target lesion revascularization (CD-TLR), a safety composite (freedom from device- and procedure-related death to 30 days, and freedom from major target limb amputation and freedom from clinically driven target vessel revascularization within 60 months), and major adverse events.
Results:
The prespecified imaging cohorts enrolled 132 de novo ISR, 158 LL, and 127 CTO participants. Kaplan-Meier estimates of freedom from CD-TLR through 5 years were 58.0% (ISR), 67.3% (LL), and 69.8% (CTO). The cumulative incidences of the composite safety endpoint were 56.0% (ISR), 65.7% (LL), and 69.8% (CTO). The 5-year freedom from all-cause mortality with vital status update were 81.4% (ISR), 75.2% (LL), and 78.2% (CTO). Within the ISR cohort, 15.9% of participants experienced 2 or more TLRs, compared with 9.5% and 5.5% in the LL and CTO groups, respectively.
Conclusions:
Results demonstrate long-term safety and effectiveness of this DCB in all 3 cohorts, with low reintervention rates in the LL and CTO cohorts and no safety issues. These results support the inclusion of this DCB into the treatment algorithm for complex femoropopliteal disease.
Background:
The purpose of this trial was to assess the safety and effectiveness of a paclitaxel-coated balloon catheter in Chinese patients with de novo or non-stented restenotic femoropopliteal atherosclerotic lesions.
Methods:
BIOLUX P-IV China is a prospective, independently adjudicated, multi-center, single-arm trial conducted in China. Patients with Rutherford class 2-4 were eligible, excluded were patients in which pre-dilation resulted in severe (≥grade D) flow-limiting dissection or residual stenosis > 70%. Follow-up assessments were conducted at 1, 6 and 12 months. The primary safety endpoint was 30-day major adverse event rate and the primary effectiveness endpoint was primary patency at 12 months.
Results:
We enrolled 158 patients with 158 lesions. Mean age was 67.6 ± 9.6 years, diabetes was present in 53.8% (n=85) and previous peripheral intervention/ surgeries in 17.1% (n=27). Lesions were 4.1±0.9 mm in diameter, and 74 ± 50 mm long with a mean diameter stenosis of 91 ± 13%; 58.2% (n=92) were occluded (core laboratory analysis). Device success was achieved in all patients. The rate of major adverse events was 0.6% [95%CI:0.0;3.5] at 30 days, consisting of one target lesion revascularization. At 12 months, binary restenosis was present in 18.7% (n=26) and target lesion revascularization was performed in 1.4% (n=2, all clinically-driven), resulting in a primary patency of 80.0% [95%CI:72.4,85.8]; no major target limb amputation occurred. Clinical improvement at 12 months, defined as improvement of at least one Rutherford class, was 95.3% (n=130). The median walking distance per 6-Minute Walk-Test was 279 m at baseline, and improved by 50 m at 30 days and by 60 m at 12 months; the visual analogue scale changed from 76.6 ±15.6 at baseline to 80.0 ±15.0 at 30 days and 78.6 ±14.6 at 12 months.
Conclusion:
Our results confirmed the clinical effectiveness and safety of a paclitaxel-coated peripheral balloon dilatation catheter for the treatment of de novo and non-stented restenotic lesion of the superficial femoral and proximal popliteal artery in Chinese patients. (NCT02912715).
Aims:
Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy.
Methods and results:
Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints.
Conclusion:
Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.
Background
Endovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS).
Objectives
To compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials.
Methods
Patient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE).
Results
The primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P < 0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months.
Conclusions
In a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis versus BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.
Endovascular procedures are frequently performed for symptomatic femoropopliteal disease. Drug-eluting stents (DES) and drug-coated balloons (DCB) were introduced to improve long-term outcomes and demonstrated superior outcomes to percutaneous transluminal angioplasty in randomised clinical trials. Femoropopliteal disease, however, can be challenging to treat using an endovascular approach as this segment suffers increased biomechanical stress during extremity movements, which may lead to chronic vascular injury or even stent fracture. The advantages of DCB include the direct and homogeneous delivery of an antiproliferative agent to the arterial wall, and the ability to reach tortuous and longer lesions without a vascular implant; however, the lack of scaffold makes the intervention prone to significant recoil. Even though the use of DCB, a leave-nothing-behind strategy, may appear desirable, the need for bailout stenting will increase as lesions become more complex. This review summarises and compares the currently available evidence regarding the use of DCB and DES in the treatment of femoropopliteal disease.
Background:
Clinical benefit of paclitaxel-coated devices for patients with peripheral arterial disease has been confirmed in randomized controlled trials (RCTs). A meta-analysis published in 2018 identified late mortality risk over a long follow-up period due to use of paclitaxel-coated devices in the femoropopliteal arteries, which caused enormous controversy and debates globally. This study aims to further evaluate the safety of paclitaxel-coated devices by incorporating the most recently published data.
Methods:
We searched for candidate studies in PubMed (MEDLINE), Scopus, EMBASE (Ovid) online databases, government web archives and international cardiovascular conferences. Safety endpoints of interest included all-cause mortality rates at one, two and five years and the risk ratio (RR) was used as the summary measure. The primary analysis was performed using random-effects models to account for potential clinical heterogeneity.
Findings:
Thirty-nine RCTs including 9164 patients were identified. At one year, the random-effects model yielded a pooled RR of 1.06 (95% CI [0.87, 1.29]) indicating no difference in short-term all-cause deaths between the paclitaxel and control groups (crude mortality, 4.3%, 214/5025 versus 4.5%, 177/3965). Two-year mortality was reported in 26 RCTs with 382 deaths out of 3788 patients (10.1%) in the paclitaxel arm and 299 out of 2955 patients (10.1%) in the control arm and no association was found between increased risk of death and usage of paclitaxel-coated devices (RR 1.08, 95% CI [0.93, 1.25]). Eight RCTs recorded all-cause deaths up to five years and a pooled RR of 1.18 (95% CI [0.92, 1.51]) demonstrated no late mortality risk due to use of paclitaxel-coated devices (crude mortality, paclitaxel 18.2%, 247/1360 versus control 15.2%, 122/805).
Conclusions:
We found no significant difference in either short- or long-term all-cause mortalities between patients receiving paclitaxel-coated and uncoated devices. Further research on the longer-term safety of paclitaxel usage (e.g., 8- or 10-year) is warranted.
Registration:
PROSPERO, CRD42021246291.
Purpose:
Although effectiveness and safety of many different paclitaxel coated balloons in the treatment of peripheral arterial disease (PAD) are extensively studied, there is a lack of direct head-to-head comparison studies. To meet this need and to avoid potential "class-effects", the BIOPACT was set up. The purpose is to demonstrate the safety and efficacy of the Passeo-18 Lux DCB (Biotronik) for treatment of patients with symptomatic PAD due to femoropopliteal lesions.
Methods:
302 patients are randomized in a 1:1 manner to treatment with either the Passeo-18 Lux DCB or the IN.PACT Admiral DCB (Medtronic) for testing of a formal non-inferiority hypothesis. The participants will be followed for 5 years. The primary efficacy endpoint is freedom from clinically-driven target lesion revascularization (CD-TLR) at 12 months, defined as any re-intervention at the target lesion due to symptoms, drop of ankle brachial index (ABI) > 20% or > 0.15 compared to post-procedural ABI. Primary safety endpoint is a composite of freedom from device/procedure-related death through 30 days post-index procedure, freedom from major target limb amputation and clinically-driven target vessel revascularization (CD-TVR) through 12 months post-index procedure. Secondary endpoints can be found at clinicaltrials.gov, ID NCT03884257.
Discussion:
As full enrolment was reached by the beginning of September, the investigators expect complete analysis of the primary endpoints by the end of 2022; Meanwhile preliminary results will be disclosed during 2022. As in terms of randomized head-to-head efficacy and safety analysis, this study on paclitaxel coated balloons may provide additional information to clinicians and healthcare providers. Trial registration ClinicalTrials.gov ID: NCT03884257 LEVEL OF EVIDENCE: Level 2, Randomized trial.
Background:
Numerous randomised controlled trials (RCTs) have demonstrated the superiority of paclitaxel drug-coated balloons (DCBs) over non-coated angioplasty balloons for treatment of femoropopliteal peripheral arterial disease (PAD). There is a paucity of clinical evidence in more complex patients who are often excluded from RCTs and long-term data up to 5 years are very limited in PAD revascularisation studies.
Aims:
This is a report of the 5-year outcomes from the prospective, single-arm, international IN.PACT Global Study. The IN.PACT Admiral DCB was evaluated for femoropopliteal atherosclerotic disease treatment in a real-world patient population.
Methods:
In total, 1,535 patients were enrolled at 64 international sites. The prespecified clinical cohort included 1,406 patients with claudication or rest pain. Patients were evaluated up to 5 years for the occurrence of adverse events and clinically driven target lesion revascularisations (CD-TLR).
Results:
The mean lesion length was 12.1±9.5 cm in 1,774 lesions, 18.0% had in-stent restenosis, 35.5% were total occlusions and 68.7% were calcified. Per independent clinical events committee adjudication, the Kaplan-Meier estimate of freedom from CD-TLR up to 5 years was 69.4%, and the restricted mean survival time to first CD-TLR was 1,470.1 days. Outcomes were similar for males and females; freedom from CD-TLR was 69.1% in females and 69.6% in males (p=0.602). The cumulative incidence of major adverse events for the clinical cohort was 45.9% and freedom from all-cause mortality with the vital status update was 78.9% up to 5 years.
Conclusions:
The IN.PACT Admiral DCB demonstrated safe and durable outcomes in real-world participants with complex femoropopliteal disease.
Clinicaltrials:
gov: NCT01609296.
In an aging population with a rising incidence of peripheral artery disease, endovascular therapy is a favorable alternative to open surgical bypass. As a minimally invasive approach, endovascular therapy incurs less physiologic stress and periprocedural complications. Balloon angioplasty and stenting have been the predominant tools in peripheral endovascular therapy. The mechanisms of endovascular therapy have evolved beyond pneumatic dilation and forcing plaque against vessel wall with angioplasty and stenting. Technology has broadened to adjunctive local treatments with pharmaceutical agents coating balloons or eluting from stents, atherectomy to remove intimal and medial plaque, and more recently, intravascular lithotripsy to fracture and modify plaque. These technologies have performed well in curated clinical trials and in the real world for short-segment disease. Despite the excellent outcomes of treatment for short-segment occlusive disease, post-procedural patency of endovascular treatment for long-segment, highly-calcified lesions remains challenging in the femoropopliteal region. The development of drug-coated balloons and stents brings the hope of improved patency. However, the results are incrementally better at best and are not superior to surgical bypass. Additionally, there is controversy regarding the long-term mortality risk. With numerous devices and techniques as well as differing magnitudes of PAD, it will be difficult to practically have a study to answer all questions regarding endovascular treatment of the femoropopliteal artery. This review examines current endovascular techniques for de novo and recurrent femoropopliteal arterial occlusive disease as well as the applicability of intravascular ultrasound and optimal stenting strategies for long-segment disease.
Purpose
Endovascular treatment of femoropopliteal arterial diseases remains controversial. We conducted a Bayesian network meta-analysis of randomized controlled trials aiming to investigate the efficacy differences between paclitaxel- or sirolimus-eluting stents, covered stents, drug-coated balloons, bare metal stents, and percutaneous transluminal angioplasty.
Method
MEDLINE, Embase, Ovid, and other relevant online material were searched up to October 21, 2020. Primary endpoints were primary patency and target lesion revascularization at 6, 12, and more than 24 months.
Results
Thirty-eight eligible trials included 6026 patients. In terms of primary patency, drug eluting stents were ranked as the most effective treatment based on the surface under the cumulative ranking curve values at 6 (80.6), 12 (78.4), and more than 24 months (96.5) of follow-ups. In terms of target lesion revascularization, drug eluting stents were ranked as the most effective treatment based on the surface under the cumulative ranking curve values at 6 (90.3), 12 (71.3), and more than 24 months (82.1) of follow-ups. Covered stents and bare metal stents had higher ranks in target lesion revascularization than those in primary patency. Sirolimus stents had a higher rank than paclitaxel stents.
Conclusion
Drug eluting stents showed encouraging results in primary patency rates and freedom from target lesion revascularization at all phases of follow-up for femoropopliteal arterial diseases. Sirolimus stents appear to be more effective in femoropopliteal segment than paclitaxel stent.
Objective
Restenosis is a common complication after endovascular treatment of peripheral artery disease. Drug-coated balloon (DCB) treatment has been proven safe and effective in reducing the rate of restenosis for simple and short lesions. However, the clinical results of DCBs for long lesions are still very limited. This study aimed to evaluate the efficacy and safety of DCBs in the treatment of long femoropopliteal artery disease. And the results of this study will also complement the existing evidence of DCB treatment of long lesions.
Methods
Patients with lesion length ≥15cm according to computed tomography angiography (CTA) or angiography in the AcoArt I Study were included into this study. Based on the balloon catheter used in treatment, patients were divided into the DCB group and the percutaneous transluminal angioplasty (PTA) group. The demographic, lesion, and procedural characteristics and 24-month follow-up results were compared between the two groups. The primary efficacy endpoints were angiographic late lumen loss (LLL) at 6 months or at the time of clinically driven target lesion revascularization (CD-TLR), primary patency (PP), freedom from CD-TLR, and changes in the ankle-brachial index (ABI) and Rutherford class during 24 months of follow-up. The safety endpoint was the occurrence of major adverse events.
Results
The total number of patients was 87, including 42 in the DCB group and 45 in the PTA group. There were no significant differences between the two groups in demographic, lesion, and procedural characteristics. The 6-month follow-up angiography showed that the LLL was significantly smaller in the DCB group than the PTA group (0.27 ± 0.90 mm vs 1.32 ± 0.91 mm; P<0.001). At 24 months, compared with the PTA group, the DCB group had a significantly higher rate of freedom from CD-TLR (81.58% vs 43.18%; P<0.001) and a significantly higher PP rate (46.88% vs 15.00%; P=0.003). The DCB group had a significantly higher ABI than the PTA group at 6, 12, and 24 months (P<0.001, P=0.004 and P=0.018, respectively). The DCB group had a better Rutherford class than the PTA group at 6 and 12 months (P=0.033 and P=0.012, respectively); the Rutherford class did not significantly differ between the two groups at 24 months (P=0.127). The incidence of major adverse events did not significantly differ between the two groups.
Conclusion
The effectiveness of the DCB is superior to a standard uncoated balloon in treating long lesions during 24 months of follow-up. Furthermore, the safety of the DCB is equivalent to that of PTA.
The field of peripheral arterial intervention has exploded over the past 20 years. Current knowledge includes a growing evidence base for treatment as well as a myriad of new interventional approaches to complex disease. This review seeks to outline the current state of the art for interventional approaches to lower extremity peripheral arterial disease.
Endovascular treatment of peripheral arterial disease has evolved and expanded rapidly over the last 20 years. New technologies have increased the diversity of devices available and have made it possible to approach even the most challenging and high-risk lesions using endovascular techniques. In this review, we examine the clinical evidence available for several categories of endovascular devices available to treated peripheral arterial disease, including intravascular lithotripsy, atherectomy, and drug-coated devices. The best application for some technologies, such as intravascular lithotripsy and atherectomies, have yet to be identified. In contrast, drug-coated devices have an established role in patients at high risk for long-term failure but have been the subject of much controversy given recent concerns over possible adverse effects of paclitaxel. Future investigation should further assess these technologies in patients with complex disease using updated staging systems and outcomes with direct clinical relevance such as functional improvement, wound healing, and freedom from recurrent symptoms.
Background:To confirm the safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) based on the indication approved by the Pharmaceuticals and Medical Devices Agency Japan in real-world patients with femoropopliteal artery disease.
Methods and Results:IN.PACT PMS Japan was a prospective, multicenter, single-arm, post-market surveillance (PMS) study conducted in Japan that enrolled 304 participants (mean age 75.3±7.9 years). The primary endpoint was primary patency at 6 months following the index procedure, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and freedom from restenosis as determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤2.4 (assessed by the independent DUS core laboratory). Secondary endpoints included acute outcomes, primary patency at 12 months post-index procedure, freedom from CD-TLR, and major adverse events at 12 months. The mean lesion length was 97.81±58.97 mm. The primary endpoint, 6-month primary patency, was 91.3% (240/263). Kaplan-Meier estimates of primary patency and freedom from CD-TLR through 12 months were 91.5% and 94.1%, respectively. The CD-TLR rate was 5.8% (14/240) with low rates of thrombosis (0.8%) and target limb amputation (0.4%) at 12 months.
Conclusions:The results of this real-world PMS study were consistent with outcomes from previous IN.PACT DCB studies, confirming the safety and efficacy of the IN.PACT Admiral DCB for broader use in patients seen in everyday practice.
Purpose
To assess the efficacy and safety of the Orchid drug-coated balloon (coated with paclitaxel) for the treatment of femoropopliteal artery disease versus percutaneous transluminal angioplasty in Chinese population.
Methods
This is a prospective, single center, single-blinded, randomized controlled trial that randomized (1:1) 60 patients (38 men; mean age 68.7 ± 8.8) to drug-coated balloon group ( n = 30) or percutaneous transluminal angioplasty group ( n = 30). The primary efficacy endpoint was primary patency of the target lesion and clinically driven target lesion revascularization (CD-TLR) at 12 months. The primary safety end point was freedom from perioperative death at 30 days and freedom from limb-related death and major amputation at 12 months.
Results
Baseline characteristics were similar between the two groups. Drug-coated balloon group resulted in higher primary patency (82.8% vs. 48.3%, p = 0.005) and lower CD-TLR rates (3.5% vs. 27.6%; p = 0.001) versus percutaneous transluminal angioplasty group at 12 months. The ABI was significantly higher in drug-coated balloon group than percutaneous transluminal angioplasty group (0.86 ± 0.13 vs. 0.72 ± 0.18, p = 0.025). There were no perioperative death at 30 days, no limb-related death and no major amputation at 12 months in either group.
Conclusions
The randomized controlled trial showed superior treatment effect with drug-coated balloon versus percutaneous transluminal angioplasty, with remarkably higher patency and lower CD-TLR rates. The result is consistent with other study and demonstrates the safety and efficacy of the Orchid drug-coated balloon for the treatment of femoropopliteal artery disease.
Background
Recent meta-analyses have raised concerns about mortality with paclitaxel drug-coated balloons. This pooled, patient-level analysis of the BIOLUX PI, P-II, and P-III studies was performed to evaluate the safety and efficacy of Passeo-18 Lux DCB.
Materials and Methods
Individual patient-level demographic, clinical, diagnostic, and procedural data from the BIOLUX PI, BIOLUX P-II, and BIOLUX P-III studies were pooled in a common database. Clinical safety (all-cause mortality and cardiovascular mortality) and efficacy (any amputation, target lesion/vessel revascularization) were extracted. Cox proportional modelling was used to assess the effect of critical limb ischemia at the time of enrollment, and the occurrence of new amputation as a time-dependent variable on mortality.
Results
A total of 1009 patients were included in the analysis. Sixty-six patients were treated with percutaneous transluminal angioplasty (PTA) and 943 underwent DCB angioplasty. The cumulative incidence of all-cause mortality did not differ between the groups (PTA 6.7%, DCB 6.7%, p = 0.65). The composite efficacy endpoint of freedom from any amputation, target lesion/vessel revascularization was superior in the DCB arm compared to PTA [PTA 28.8%, DCB 16.7%, p = 0.02]. Both in unadjusted and adjusted Cox proportional models (adjusted for critical limb ischemia and amputation), the use of DCB was not associated with any mortality at 1 year.
Conclusions
Our patient-level analysis shows that overall the use of the Passeo-18 Lux paclitaxel DCB in infrainguinal arteries was not associated with increased mortality at 1 year and reinforces the efficacy of DCB angioplasty in preventing amputation or the need for reintervention.
Objectives
: This study aims to assess the use of drug-coated balloon (DCB) in a large patient population under real-world conditions and, specifically, analyse the impact of diabetes mellitus on long term outcomes following DCB utilisation.
Methods
: BIOLUX P-III is a prospective, international, multicentre, registry that was conducted at 41 centres. The present study is a 24-month subgroup analysis of patients with diabetes mellitus having infrainguinal lesions treated with the Passeo-18 Lux DCB. The primary endpoints were freedom from major adverse events (MAEs) within 6 months of intervention and freedom from clinically driven target lesion revascularisation (CD-TLR) within 12 months of intervention.
Results
: Of the 882 patients in the registry, 418 had diabetes (516 lesions). Most diabetics had concomitant hypertension (88.8%) and hyperlipidaemia (70.3%). Insulin dependence was observed in 48.8% of diabetics. Moreover, smoking (62.2%) and chronic renal insufficiency (41.9%) were also found to be common in this cohort. Chronic limb threatening ischemia (Rutherford class ≥4) was present in 53.1% of all patients. 22.9% of lesions were infrapopliteal, while 22.5% of lesions were treated for in-stent restenosis. The mean target lesion length was 85.6 ± 73.2 mm, and 79.4% of lesions were calcified (of which 17.9% were heavily calcified). Overall, device success was 99.7%. Freedom from MAEs was 90.5% (95% confidence interval (95% CI): 87.2–93.0) at 6 months, 85.4% (95% CI: 81.5–88.6) at 12 months and 80% (95% CI: 75.5–83.8) at 24 months. Freedom from CD-TLR was 95.9% (95% CI: 93.8–97.4), 91.6% (95% CI: 88.7–93.8), and 87.1% (95% CI: 83.5–89.9) at 6, 12, and 24 months, respectively. All-cause mortality at 24 months in diabetics was 16.0% (95% CI: 12.6–20.2), and major target limb amputation was 6.1% (95% CI: 4.1–8.9), which was significantly higher than in non-diabetics (8.4% (95% CI: 6.0–11.6), p = 0.0005 and 1.2% (95% CI: 0.5–2.9), p <0.0001, respectively). At 24 months, 82.0% of patients had improved by ≥1 Rutherford class.
Conclusion
: Treatment of a real-world diabetic patient population with the Passeo-18 Lux DCB resulted in high efficacy and low complication rates, despite the fact that diabetic patients usually suffer from a multitude of concomitant comorbidities.
Clinical Trial Registration
: NCT02276313
Object
The study sought to compare the safety and effectiveness of drug-coated balloon(DCBs) with bare nitinol stent in patients with complex femoropopliteal(FP) lesions in real-world practice.
Methods
Patients with symptomatic (Rutherford stage 2 to 5) femoropopliteal lesions who underwent DCB or bare nitinol stent implantation at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital from June 2016 to September 2017 were included. Demographics, angiographic and procedural variables were included. Freedom from target lesion revascularization (TLR), primary patency and major adverse events were obtained from follow-up results at 3,6 and12 months. Descriptive analysis was performed on all variables.
Results
A total of 90 eligible patients were enrolled, which included 51 DCB subjects (mean age, 63.1±13.2 years; 76.5% male) with 55 lesions and 39 nitinol stent subjects (mean age, 66.5±10.5 years; 61.5% male) with 42 lesions. Significant higher primary patency was observed in the DCB group compared with the stent group (74.5% versus 52.4%; log-rank test p=0.018; HR 0.335, 95%CI 0.124-0.903, p=0.031). The rates of freedom from TLR (f-TLR) were 78.2% and 59.5% (log-rank test p=0.032) for the DCB group and the stent group, respectively, at 12 months. CD-TLR rates were 18.2% versus 38.1% with a p-value of 0.023. Female sex (HR 6.122, 95%CI 1.880-19.934, p=0.003), lesion length over 20cm (HR 5.514, 95%CI 2.312-13.148, p<0.001) and renal insufficiency (HR 2.609, 95%CI 1.087-6.260, p=0.032) were suggested as independent risk factors of reducing primary patency. There were no significant differences in major adverse events between the two groups.
Conclusion
The result above demonstrates that DCB treatment has higher primary patency and lower TLR at 12 months than nitinol stent. These data confirm the safety and effectiveness of the DCB for patients with complex femoropopliteal lesions.
Although paclitaxel-based devices which demonstrated improved outcomes in the treatment of lower-extremity peripheral artery disease (PAD) have been used worldwide, Katsanos et al. reported a systematic review and summary-level meta-analysis of RCTs in which application of paclitaxel-based devices in the femoropopliteal artery was associated with an increased mortality risk. The purpose of this study was to describe the safety of endovascular therapy (EVT) using paclitaxel-coated stents for femoropopliteal disease by evaluating the mortality risk compared with patients treated with paclitaxel-free devices. A retrospective, multicenter, non-randomized study examined 481 de-novo symptomatic PAD patients treated in 13 Japanese medical centers from January 2011 to December 2015. The risk of all-cause mortality was analyzed between the 65 patients treated with a paclitaxel-coated stent (PTX-coated group) and 416 patients treated with an uncoated balloon or bare nitinol stent (PTX-free group). Overall survival of the PTX-coated group and the PTX-free group were compared after propensity score matching. The 2-year overall survival estimates were 87.7% in the PTX-coated group vs 88.7% in the PTX-free group. There were no significant differences in the mortality risk between the groups through a full follow-up of 2 years (p = 0.80). The multivariate cox proportional hazards model identified three significant predictors of mortality; age (HR, 1.08; 95% CI, 1.03–1.13; p = 0.002), hemodialysis (HR, 3.16; 95% CI, 1.34–7.42; p = 0.008), and albumin (g/dl) (HR, 0.46; 95% CI, 0.25–0.85; p = 0.01).
Objective
Primary nitinol stenting (PNS) and drug coated balloon angioplasty (DCB) are two of the most common endovascular interventions for femoropopliteal atherosclerotic disease. While many prospective randomized controlled trials have compared PNS or DCB to plain balloon angioplasty (POBA), no studies have directly compared PNS against DCB therapy. The purpose of this network meta-analysis is to determine whether there is a significant difference in outcomes between PNS and DCB.
Methods
The primary outcome measure was binary restenosis, the secondary outcome measures were target lesion revascularization (TLR) and change in ankle brachial index (ABI). Outcomes were evaluated at 6, 12, and 24 months. A literature review identified all randomized controlled trials published prior to March 2020 that compared DCB to POBA or PNS to POBA in the treatment of native atherosclerotic lesions of the femoropopliteal artery. Studies were excluded if they contained in-stent stenosis or tibial artery disease that could not be delineated out in a subgroup analysis. Network meta-analysis was performed using the network and mvmeta commands in STATA 14.
Results
Twenty-seven publications covering 19 trials were identified, eight trials compared PNS to POBA and 11 trials compared DCB to POBA. The odds of freedom from binary restenosis for patients treated with DCB compared to PNS at 6 months was 1.19 (95% CI 0.63 – 2.22), at 12 months was 1.67 (95% CI 1.04 – 2.68), and at 24 months was 1.36 (95% CI 0.78 – 2.37). The odds of freedom from target lesion revascularization for patients treated with DCB compared to PNS at 6 months was 0.66 (95% CI 0.12 – 3.80), at 12 months was 1.89 (95% CI 1.04 – 3.45), and at 24 months was 1.68 (95% CI 0.82 – 3.44). The mean increase in ABI for patients treated with PNS compared to DCB at 6 months was 0.06 higher (95% CI -0.03 – 0.15), at 12 months was 0.05 higher (95% CI 0.00 – 0.09), and at 24 months was 0.07 higher (95% CI -0.01 – 0.14).
Conclusion
Both DCB and PNS demonstrated a lower rate of binary restenosis compared to POBA at the 6-month, 12-month, and 24-month timepoints. When comparing DCB to PNS through network meta-analysis, DCB had a statistically lower rate of a binary restenosis and target lesion revascularization at the 12-month timepoint. This network meta-analysis demonstrates that both DCB and PNS are superior to POBA, and that PNS is a satisfactory substitute for DCB when paclitaxel is not desirable.
Background
Drug-coated balloons (DCB) have demonstrated satisfactory clinical results in the treatment of femoropopliteal artery diseases.
Objective
To evaluate the efficacy and safety of the Reewarm™ PTX DCB in the treatment of femoropopliteal artery lesions compared with plain balloon.
Methods
This was a multi-center, parallel-group, randomized controlled trial in patients with femoropopliteal artery lesions in China,. The participants were randomized 1:1 to percutaneous transluminal angioplasty with Reewarm™ PTX DCB or with standard plain balloon (PTA group) after pre-dilatation with a residual stenosis less than 70%. The primary endpoint was late lumen loss (LLL) at 6 months in the intent-to-treat set. The secondary endpoints included the target lesion revascularization (TLR) and major advance events(MAE)rate at 12 months.
Results
Between July 2014 and April 2017, a total of 200 patients were enrolled. The mean age of the subjects was 67.8 ± 9.2 years in the DCB group (n = 100) and 69.4 ± 10.3 years in the PTA group (n = 100). The LLL at 6 months in the DCB group was significantly lower than in the PTA group (0.5 ± 0.8 mm vs. 1.5 ± 1.2 mm, P < 0.001). The TLR rate in the DCB group was lower than in the PTA group at 12 months (15.0% vs. 29.0%, P < 0.05). The occurrence of MAE⁴ in the DCB group by 12 months was lower than in the PTA group (23.0% vs. 38.0%, P < 0.05).
Conclusion
Reewarm-PTX drug-coated balloon is associated with better efficacy and safety than the plain balloon for femoropopliteal lesion.
Purpose:
The BIOLUX P-III registry was initiated to further assess the safety and efficacy of the Passeo-18 Lux drug-coated balloon (DCB) in infrainguinal lesions in a real-world environment and in prespecified risk groups.
Materials and methods:
BIOLUX P-III is a prospective, global, all-comers registry with patients treated under real-world conditions. We herein report 24-month results of the prespecified subgroup of 151 patients with 185 below-the-knee (BTK) lesions. The primary safety and efficacy endpoints were freedom from major adverse events (a composite of freedom from device and procedure mortality through 30 days, major target limb amputation and clinically driven target lesion revascularization) at 6 months and freedom from clinically driven target lesion revascularization (FfTLR) at 12 months.
Results:
At baseline, 76.0% of patients had critical limb ischemia and 48.9% of lesions were TASC C or D lesions. Technical success was achieved in 97.8%, and bailout stenting was required in 1.1%. Freedom from major adverse events was 86.2% [95% CI 79.4; 90.8] at 6 months, and FfTLR was 90.9% [95% CI 85.2; 94.4] at 12 months. At 24 months, FfTLR was 90.9% [95% CI 85.2; 94.4], freedom from major amputation was 90.1% [95% CI 83.9, 94.0], and overall survival was 79.2% [70.7, 85.5]. There was a significant clinical improvement (mean Rutherford class improvement of - 2.9 ± 1.9, p < 0.0001) and an improvement in pain (mean improvement on Wong-Baker Faces Pain Scale of - 2.7 ± 2.9, p < 0.0001).
Conclusions:
In this real-world DCB registry, 24-month outcomes of Passeo-18 Lux demonstrated safety and efficacy in BTK lesions with high patency rates and sustained clinical improvements at 24 months.
Trial registration:
NCT02276313.
Objectives:
The aim of the BIOLUX P-III (A Prospective, International, Multi-Centre, Post-Market All-Comers Registry to Assess the Clinical Performance of the Passeo-18 Lux Paclitaxel Releasing Balloon Catheter in Infrainguinal Arteries - III) registry was to collect real-world data on the Passeo-18 Lux paclitaxel-coated balloon.
Background:
Critical limb ischemia (CLI) is a severe condition associated with high morbidity and mortality. Prospective data are needed to provide further insights on drug-eluting devices.
Methods:
BIOLUX P-III is a prospective, post-market, all-comers registry assessing the safety and performance of the Passeo-18 Lux. Clinical information was collected at 6, 12, and 24 months. The authors report 24-month outcomes of the CLI subgroup with patients in Rutherford classes 4 to 6.
Results:
The CLI subgroup included 328 patients with 422 lesions. Patients were 71.1 ± 10.5 years of age, and 61.0% had diabetes. Femoropopliteal lesions were present in 53.8% (n = 227), below-the-knee lesions were present in 27.0% (n = 114), and lesions were moderate or heavily calcified in 45.0% (n = 190). Major adverse events, defined as 30-day device- or procedure-related mortality, major target limb amputation, and clinically driven target lesion revascularization, occurred in 9.8% of patients through 6 months, in 14.9% through 12 months, and in 19.4% through 24 months. Clinically driven target lesion revascularization occurred in 4.4%, 8.5%, and 12.1%, major amputation in 4.9%, 5.2%, and 6.1%, and mortality in 8.1%, 11.1%, and 20.1%, respectively. Predictors of mortality were age ≥75 years and higher Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class, and higher Rutherford class was associated with increased mortality and amputation rates.
Conclusions:
In a large, multimorbid patient population with complex lesions and CLI, the safety and performance of the Passeo-18 Lux paclitaxel-coated balloon has been confirmed, with low rates of major amputation and target lesion revascularization.
Objectives:
Femoropopliteal chronic total occlusions are challenging to treat, and evidence of the effectiveness of drug-coated balloon angioplasty for long femoropopliteal chronic total occlusion lesions is limited. We compared the midterm outcomes of drug-coated balloon angioplasty versus plain old balloon angioplasty (POBA) for femoropopliteal chronic total occlusions.
Methods:
In total, 95 patients from the AcoArt I trial (ClinicalTrials.gov identifier NCT01850056) with ≥5-cm femoropopliteal chronic total occlusion lesions were enrolled in this post-hoc subset analysis (drug-coated balloon, n = 50; POBA, n = 45). The primary endpoints were primary patency and clinically driven target lesion revascularization (CD-TLR) at 24 months. The secondary endpoints were late lumen loss at six months and binary restenosis, major adverse events (composite of death and target limb amputation), change in the Rutherford class, and the ankle-brachial index at 24 months.
Results:
Demographic, clinical, and lesion characteristics were matched (mean lesion length, 20 cm). The six-month late-lumen loss rate was lower in the drug-coated balloon than POBA group (0.18 ± 0.81 vs. 1.34 ± 0.94 mm, respectively; P < 0.001). The 24-month primary patency rate was significantly higher in the drug-coated balloon than POBA group (53.85% vs. 17.50%, respectively; P < 0.001). The CD-TLR rate in the drug-coated balloon and POBA groups was 12.77 and 45.24%, respectively (P = 0.002). The 24-month overall mortality rate in the drug-coated balloon and POBA groups was 12.77% and 6.98%, respectively (P = 0.360), with no device- or procedure-related deaths. One major amputation had occurred in each group by the 24-month follow-up.
Conclusion:
The paclitaxel drug-coated balloon shows better primary patency and freedom from target lesion revascularization than POBA at 24 months after treatment of femoropopliteal chronic total occlusions (≥5 cm) lesion.
Objectives
We aimed to evaluate whether paclitaxel eluting devices increased the risk of death in patients undergoing revascularization for infrainguinal peripheral artery disease using network meta‐analyses.
Methods
PUBMED and EMBASE were searched through April 2020 for randomized trials in patients with infrainguinal peripheral artery disease who underwent revascularization with or without a paclitaxel eluting device (balloon/stent). Short‐term mortality defined as death at 6–12 months, and long‐term mortality defined as death at >12 months after revascularization.
Results
Our search identified 57 eligible randomized controlled studies enrolling a total of 9,362 patients comparing seven revascularization strategies (balloon angioplasty vs. bare metal stent vs. covered stent vs. paclitaxel eluting stent vs. other drug eluting stent vs. paclitaxel‐coated balloon vs. bypass surgery). Overall, paclitaxel eluting stent and paclitaxel‐coated balloons did not increase short‐term mortality (e.g., vs. balloon angioplasty: paclitaxel‐coated balloon OR [95% CI] 1.21 [0.88–1.66], p = .24; paclitaxel eluting stent OR [95%CI] 1.01 [0.63–1.63], p = .97, respectively). In addition, paclitaxel eluting stent did not show significant increase in long‐term mortality (e.g., vs. balloon angioplasty: OR [95%CI] 1.06 [0.70–1.59], p = .79). However, paclitaxel‐coated balloon showed significant increase in long‐term mortality compared to balloon angioplasty and bypass (vs. balloon angioplasty: OR [95% CI] 1.48 [1.06–2.07], p = .021; vs. bypass: OR [95%CI] 1.73 [1.05–2.84], p = .031, respectively).
Conclusions
In this meta‐analysis of randomized trials, there was no significant increase in mortality with paclitaxel eluting stent, but there was increased risk of long‐term mortality in paclitaxel‐coated balloon for the treatment of infrainguinal peripheral artery disease.
Purpose: To evaluate the safety and efficacy of the novel SELUTION sustained-limus-release (SLR) drug-eluting balloon (DEB) in the treatment of femoropopliteal lesions. Materials and Methods: Between October 2016 and May 2017, 50 subjects (mean age 69.6±10.4 years; 29 men) with symptomatic moderate to severe lower limb ischemia (Rutherford categories 2 or 3) were enrolled at 4 German centers for the SELUTION SLR first-in-human trial ( ClinicalTrials.gov NCT02941224). The SELUTION SLR utilizes micro-reservoirs (biodegradable polymer spheres containing sirolimus) embedded within an amphipathic membrane coated onto an angioplasty balloon. The biodegradable reservoirs are transferred to the target vessel lumen during brief balloon inflation. The primary trial objective was comparison of angiographic late lumen loss at 6 months against an objective performance criterion (OPC) value of 1.04 mm for uncoated balloon angioplasty. Secondary endpoints included device, procedural, and clinical success; clinical and imaging assessments of primary patency and restenosis; functional assessments including Rutherford category and ankle-brachial index (ABI); and major adverse events [composite of cardiovascular mortality, index limb amputation, target limb thrombosis, and clinically-driven target lesion revascularization (CD-TLR)]. Results: At 6 months, median angiographic late lumen loss following SELUTION SLR treatment was 0.19 mm (range −1.16 to 3.07). Mean angiographic late lumen loss (n=34) was 0.29±0.84 mm (95% CI −0.01 to 0.58), significantly lower than the 1.04-mm OPC value (p<0.001). The rate of primary patency by duplex ultrasound was 88.4%, and freedom from angiographic binary restenosis was 91.2%. Through 6 months, there was significant improvement over baseline in Rutherford categories (p<0.001) and in ABI measurements (p<0.001). A single case (2%) of CD-TLR occurred at 5 months. There were no other major adverse events. Conclusion: Through 6 months, the SELUTION SLR DEB appears to inhibit restenosis effectively and safely, improving outcomes in subjects with symptomatic femoropopliteal disease.
Even if recently the first positive results were presented for a paclitaxel releasing drug eluting stent there are still concerns about stent implantation in the femoro-popliteal artery. This makes any stentless technology attractive that achieves at least as good acute and longer term results in this vessel area. Three randomized studies investigating the value of short time paclitaxel release using a drug coated balloon gave promising results with significantly improved patency rates compared to plain balloon angioplasty in femoro-popliteal lesions and at least as good patency results as for the majority of bare metal nitinol stents (THUNDER, FEMPAC, LEVANT 1). Below-the-knee this promising concept is still under evaluation (PICCOLO study) whereas the first positive results for drug eluting stents in shorter lesions had been recently presented (YUKON BTK, DESTINY). This article gives an overview upon already published and presented data and still ongoing trials on drug releasing balloons in the peripheral arteries.
The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux , 0.61 ± 0.20 mm with Elutax , and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups.
Endovascular therapy is a rapidly evolving field for the treatment of patients with peripheral arterial disease, and a magnitude of studies reporting on various modern revascularization concepts have been recently published. Thus, studies assessing the efficacy of endovascular therapy of peripheral arteries do not operate with uniformly defined endpoints, rendering a direct comparison of studies difficult. The purpose of this consensus statement is to highlight differences in the terminology used in the current literature and to propose some standardized criteria that must be considered when reporting results of endovascular revascularization for chronic ischaemia of lower limb arteries.
Drug-eluting stents reduce restenosis in coronary arteries, but clinical trials have failed to prove their efficacy in peripheral arteries. We investigated the use of paclitaxel-coated angioplasty balloons and paclitaxel dissolved in the angiographic contrast medium during angioplasty of the leg.
In a small, multicenter trial, we randomly assigned 154 patients with stenosis or occlusion of a femoropopliteal artery to treatment with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control). The primary end point was late lumen loss at 6 months.
The mean (+/-SD) age of the patients was 68+/-8 years, 24% were smokers, and 49% had diabetes. Twenty-seven percent of the lesions were total occlusions, and 36% were restenotic lesions. The mean lesion length was 7.4+/-6.5 cm. There were no significant differences in baseline characteristics between the groups. There were no adverse events attributable to the paclitaxel-coated balloons. At 6 months, the mean late lumen loss was 1.7+/-1.8 mm in the control group, as compared with 0.4+/-1.2 mm (P<0.001) in the group treated with paclitaxel-coated balloons and 2.2+/-1.6 mm (P=0.11) in the group treated with paclitaxel in the contrast medium. The rate of revascularization of target lesions at 6 months was 20 of 54 (37%) in the control group, 2 of 48 (4%) in the group treated with paclitaxel-coated balloons (P<0.001 vs. control), and 15 of 52 (29%) in the group treated with paclitaxel in the contrast medium (P=0.41 vs. control); at 24 months, the rates increased to 28 of 54 (52%), 7 of 48 (15%), and 21 of 52 (40%), respectively.
Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization. No significant benefit is seen with the use of a paclitaxel-containing contrast medium. (ClinicalTrials.gov number, NCT00156624 [ClinicalTrials.gov].).
This study sought to evaluate the safety and efficacy of the Lutonix drug-coated balloon (DCB) coated with 2 μg/mm(2) paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions.
Percutaneous treatment of peripheral vascular disease is associated with a high recurrence. Paclitaxel-coated balloons at 3 μg/mm(2) formulated differently have shown promising results with reduced restenosis.
Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were randomized between June 2009 and December 2009 to treatment with Lutonix DCB (n = 49) versus uncoated balloons (control group [n = 52]), stratified by whether balloon-only treatment (n = 75) or stenting (n = 26) was intended. The primary endpoint was angiographic late lumen loss at 6 months. Secondary outcomes included adjudicated major adverse events (death, amputation, target lesion thrombosis, reintervention), functional outcomes, and pharmacokinetics.
Demographic, peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 8.1 ± 3.8 cm and 42% total occlusions. At 6 months, late lumen loss was 58% lower for the Lutonix DCB group (0.46 ± 1.13 mm) than for the control group (1.09 ± 1.07 mm; p = 0.016). Composite 24-month major adverse events were 39% for the DCB group, including 15 target lesion revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon group, with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths. Pharmacokinetics showed biexponential decay with peak concentration (Cmax) of 59 ng/ml and total observed exposure (AUCall) of 73 ng h/ml. For successful DCB deployment excluding 8 malfunctions, 6-month late lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24%.
Treatment of femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss with safety comparable to that of control angioplasty. (LEVANT I, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis; NCT00930813).
Aims:
Safety and efficacy of percutaneous coronary interventions using the Pantera Lux paclitaxel-coated balloon have been demonstrated in the PEPPER first-in-man trial. This prospective, multicentre, clinical registry aims to evaluate its safety and efficacy in an international real-world setting in a larger cohort of patients.
Methods and results:
Between April 2010 and April 2011, 1,064 patients were treated for predominantly diffuse and proliferative in-stent restenosis of bare metal stents (BMS-ISR) and drug-eluting stents (DES-ISR), or for de novo lesions. Clinical device success was obtained in 98.2% of the patients. The study endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction and clinically driven target vessel revascularisation, and was 8.5% in the overall, 6.0% in the BMS-ISR, 11.5% in the DES-ISR and 7.0% in the de novo population at six months, and 15.1%, 11.6%, 20.6% and 9.4% at 12 months, respectively. Definitive stent thrombosis occurred in 0.4% of the patients within 12 months.
Conclusions:
Safety and efficacy of the Pantera Lux paclitaxel-coated balloon was confirmed in a real-world setting with low major adverse cardiac event rates in patients with in-stent restenosis or de novo lesions. (ClinicalTrials.gov: NCT01081366).
Purpose:
To investigate the impact of using paclitaxel-coated balloons (PCB) on outcome after post-angioplasty dissection in femoropopliteal arteries.
Methods:
The angiograms obtained in the THUNDER study (ClinicalTrials.gov identifier NCT00156624) were analyzed to compare degrees of dissection and angiographic parameters between the control (uncoated balloons, n=43) and treatment (PCBs, n=43) groups before and after the intervention and at 6-month follow-up. Furthermore, target lesion revascularizations (TLR) were documented up to 2 years.
Results:
In each group, 24 (56%) patients had a dissection after the intervention. At the 6-month follow-up, patients with dissection of any grade after treatment with PCBs had significantly less late lumen loss (0.4 mm) than patients with dissection after treatment with uncoated balloons (1.9 mm, p=0.001) and a lower degree of stenosis (20% vs. 51%, respectively; p=0.003). Patients with severe dissection (grades C, D, or E) especially seemed to benefit from the PCBs, with late lumen loss of 0.4 mm vs. 2.4 mm for controls (p=0.05). The binary restenosis rate was also markedly lower in the PCB group (20%) than in the uncoated group (55%, p=0.02). In the 2-year follow-up, TLR was performed in 56% of patients in the control group compared to 10% of patients in the PCB group (p=0.002).
Conclusion:
The results of this subgroup analysis suggest that patients with dissection following treatment with a paclitaxel-coated balloon have a very acceptable outcome and stent implantation is not necessary as long as the dissection does not result in acute flow limitation.
Background:
Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally.
Methods:
We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC).
Findings:
34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112,027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45-49 years was 5·28% (95% CI 3·38-8·17%) in women and 5·41% (3·41-8·49%) in men, and at age 85-89 years, it was 18·38% (11·16-28·76%) in women and 18·83% (12·03-28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% [2·04-4·07%] at 45-49 years and 14·94% [9·58-22·56%] at 85-89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% [4·86-8·15%] of women aged 45-49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39-3·09) in HIC and 1·42 (1·25-1·62) in LMIC, followed by diabetes (1·88 [1·66-2·14] vs 1·47 [1·29-1·68]), hypertension (1·55 [1·42-1·71] vs 1·36 [1·24-1·50]), and hypercholesterolaemia (1·19 [1·07-1·33] vs 1·14 [1·03-1·25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC.
Interpretation:
In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease.
Funding:
Peripheral Arterial Disease Research Coalition (Europe).
This study aimed to appraise 2-year outcomes after percutaneous treatment of femoropopliteal artery disease with paclitaxel-eluting balloons.
Percutaneous transluminal angioplasty with paclitaxel-eluting balloons for femoropopliteal artery disease has provided favorable 1-year results.
Consecutive patients with Rutherford class 2 to 4 disease due to femoropopliteal lesions ≤15 mm long and with 3- to 7-mm reference vessel diameter were prospectively enrolled in a multicenter registry. Endpoints of interest included primary patency, major adverse events (the composite of death, amputation, or target lesion revascularization), changes in Rutherford class, ankle-brachial index, absolute claudication distance, and quality of life after ≥24 months.
A total of 105 patients (114 lesions) treated with paclitaxel-eluting balloons and provisional stenting were enrolled, and final procedural success was obtained in all. Follow-up after 27 ± 3 months was obtained in 98 (93.3%) patients, showing that primary patency was maintained in 71 (72.4%), and major adverse events had occurred in 17 (17.5%), with persistently significant benefits in Rutherford class, ankle-brachial index, absolute claudication distance, and quality of life (all p < 0.001). Secondary patency rate was achieved in 89 cases (84.7%).
PEBs are associated with favorable functional and clinical outcomes at 2 years in patients with femoropopliteal artery disease requiring percutaneous revascularization.
Background:
Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention. A drug-eluting balloon (DEB) based on a novel coating was compared with uncoated balloons in patients undergoing femoro-popliteal percutaneous transluminal angioplasty.
Methods and results:
Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminal angioplasty were randomized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons. The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses. Secondary end points were binary restenosis and Rutherford class change at 6 months, and target lesion revascularization plus major adverse clinical events (major adverse events=death, target limb amputation, or target lesion revascularization) at 6 and 12 months. Eighty-five patients (91 cases=interventional procedures) were randomized in 3 hospitals (44 to DEB and 47 to uncoated balloons). Average lesion length was 7.0 ± 5.3 and 6.6 ± 5.5 cm for DEB and control arm, respectively. Procedural success was obtained in all cases. Six-month quantitative angiography showed that DEB were associated with significantly lower late lumen loss (-0.01 mm [95% CI, -0.29; 0.26] versus 0.65 mm [0.37; 0.93], P=0.001) and fewer binary restenoses (3 [8.6%] versus 11 [32.4%], P=0.01). This translated into a clinically relevant benefit with significantly fewer major adverse events for DEB versus uncoated balloons up to 12 months (3 [7.1%] versus 15 [34.9%], P<0.01) as well as target lesion revascularizations (3 [7.1%] versus 12 [27.9%], P=0.02).
Conclusions:
Use of IN.PACT Pacific DEB is associated with significant reductions in late lumen loss and restenoses at 6 months, and reinterventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 year of follow-up.
Clinical trial registration:
URL http://www.clinicaltrials.gov. Unique identifier: NCT01083030.
Coronary in-stent restenosis (ISR) continues to be a therapeutic challenge especially after drug eluting stent (DES) implantation. We studied patients with ISR to investigate safety and efficacy of a novel drug coated balloon (DCB) incorporating paclitaxel into a microcrystalline structure by applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective First-in-Man trial.
Eighty-one patients were enrolled at 9 European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and 38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss (LLL) independently assessed by a quantitative coronary angiography laboratory at 6 months. A secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, non-fatal myocardial infarction, clinically driven target vessel revascularization after 6 and 12 months.
At 6 months, overall LLL was 0.07±0.31 mm showing differences in BMS-ISR and DES-ISR treatment (-0.05±0.28 mm vs. 0.19±0.29 mm, respectively, P=.001). Overall MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one myocardial infarction, and no cardiac death nor stent thrombosis had occurred.
Application of a novel paclitaxel coated balloon using BTHC as an excipient in patients with ISR is safe and results in very low LLL, revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov:NCT00961181).
This study evaluated the use of a paclitaxel-eluting balloon (PEB) for treatment of femoropopliteal arterial disease.
Conventional balloon angioplasty and stenting in this setting is associated with high restenosis rates within 12 months. Recent data suggest that PEB use may reduce restenosis. Twelve-month outcomes following PEB use with provisional stenting are described.
This prospective registry enrolled patients (Rutherford class 2 to 4) with reference vessel diameter of 3 to 7 mm and lesion/occlusion length ≤ 15 cm. Endpoints included primary patency rate, target lesion revascularization, and changes in Rutherford class and ankle-brachial index. Walking capacity, absolute claudication distance, and quality of life were also assessed.
The registry enrolled 105 patients. Baseline ankle-brachial index was 0.56 ± 0.15. Baseline Rutherford classification was class 2 or 3 for most patients (91.5%). Most lesions were located in the superficial femoral artery (77.1%). Mean lesion length was 76.3 ± 38.3 mm; 29.8% of lesions were total occlusions. The device was successfully used in all patients and only 12.3% of lesions required stenting. At 12-month follow-up, 92 of 105 patients (87.6%) were evaluable; the primary patency rate was 83.7%; the target lesion revascularization rate was 7.6%; 85.6% of patients were Rutherford class 0 or 1; and mean ankle-brachial index was 0.86 ± 0.15. Quality of life and absolute claudication distance showed significant improvement from baseline to 12-month follow-up.
PEB treatment of femoropopliteal arterial disease resulted in consistent clinical improvement across multiple endpoints with a low rate of stenting and target lesion revascularization.
Despite advances in contemporary stent technology, in-stent restenosis (ISR) remains the major limitation following revascularization procedures. We developed a porcine model of ISR to specifically investigate the preclinical outcomes of a novel drug-eluting balloon (DEB) in this particular setting. Fifteen pigs received bare metal stents in each of the major coronary arteries for 28 days to induce neointimal growth. Following repeat angiography, animals were allocated to fourdifferent treatment groups. The control group consisted of a bare angioplasty catheter, while the Pantera Lux(TM), cursive (3.0 µg/mm(2) paclitaxel) (30 s inflation) was compared to two consecutive deployments of the Pantera Lux(TM), cursive (60 s inflation each) and the commercial SeQuent® Please balloon (60 s inflation). Twenty-eight days following balloon deployment, the animals underwent repeat angiography and were subsequently sacrificed for histopathologic assessment. There was a trend in reduction of percent diameter stenosis in the DEB group versus control (13.9% vs. 20.4%), while longer inflation duration or consecutive DEB deployment had no additional growth-limiting effect. Neointimal thickness was reduced from 0.38 ± 0.13 to 0.30 ± 0.09 mm in the control versus DEB group. All DEB groups showed delayed vascular healing characterized by dose-dependent increases in fibrin deposition and neointimal cell vacuity. Investigation of DEB in a porcine model of ISR is feasible and more accurately represents human disease conditions. The magnitude of neointima suppression is lower than that observed in non-diseased animal models and is accompanied by delayed vascular healing.
Sustained benefits of drug-eluting stents in femoropopliteal arteries have not been demonstrated. This prospective, multinational, randomized study was designed to compare the 12-month safety and effectiveness of a polymer-free, paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients with femoropopliteal peripheral artery disease.
Patients were randomly assigned to primary DES implantation (n=236) or PTA (n=238). Demographics and lesion characteristics were similar between groups (eg, average lesion length, approximately 65±40 mm). One hundred twenty patients had acute PTA failure and underwent secondary random assignment to provisional DES (n=61) or BMS (n=59). Primary end points were the 12-month rates of event-free survival and patency in the primary DES and PTA groups. Compared with the PTA group, the primary DES group exhibited superior 12-month event-free survival (90.4% versus 82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the primary hypotheses. In the secondary evaluations, (1) the primary DES group exhibited superior clinical benefit compared with the PTA group (88.3% versus 75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%, P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate (both DES and BMS) was 0.9% (4/457).
Femoropopliteal peripheral artery disease treatment with the paclitaxel-eluting stent was associated with superior 12-month outcomes compared with PTA and provisional BMS placement.
The success of percutaneous intervention in peripheral arterial disease is limited by restenosis. The aim of the present pilot study was to evaluate a novel method of local drug delivery.
This randomized multicenter study with blinded reading enrolled 87 patients in Rutherford class 1 to 4 with occlusion or hemodynamically relevant stenosis, restenosis, or in-stent restenosis of femoropopliteal arteries. Treatment was performed by either conventional uncoated or paclitaxel-coated balloon catheters. The primary end point was late lumen loss at 6 months. Secondary end points included restenosis rate, ankle brachial index, Rutherford class, target lesion revascularization, and tolerance up to >18 months. Before intervention, there were no significant differences in lesion characteristics such as reference diameter (5.3+/-1.1 versus 5.2+/-1.0 mm), degree of stenosis (84+/-11% versus 84+/-16%), proportion of restenotic lesions (36% versus 33%), and mean lesion length (5.7 cm [0.8 to 22.6 cm] versus 6.1 cm [0.9 to 19.3 cm]) between treatment groups. The 6-month follow-up angiography performed in 31 of 45 and 34 of 42 patients showed less late lumen loss in the coated balloon group (0.5+/-1.1 versus 1.0+/-1.1 mm; P=0.031). The number of target lesion revascularizations was lower in the paclitaxel-coated balloon group than in control subjects (3 of 45 versus 14 of 42 patients; P=0.002). Improvement in Rutherford class was greater in the coated balloon group (P=0.045), whereas the improvement in ankle brachial index was not different. The difference in target lesion revascularizations between treatment groups was maintained up to >18 months. No adverse events were assessed as related to balloon coating.
In this pilot trial, paclitaxel balloon coating caused no obvious adverse events and reduced restenosis in patients undergoing angioplasty of femoropopliteal arteries.
Recommended standards for analyzing and reporting on lower extremity ischemia were first published by the Journal of Vascular Surgery in 1986 after approval by the Joint Council of The Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. Many of these standards have been accepted and are used in the current literature on peripheral arterial occlusive disease. With the passage of time, some oversights, aspects that require clarification, and better modifications have been recognized. This report attempts to correct these shortcomings while reinforcing those recommendations that have proven satisfactory. Explanatory comments are added to facilitate understanding and application. This version is intended to replace the original version.
This analysis proposes safety and performance goals for prospective single-arm trials of bare nitinol stents to treat patients with debilitating claudication associated with femoropopliteal (FP) atherosclerotic lesions.
To date there have been no analyses of clinical trials data to set efficacy and safety benchmarks for new bare nitinol stents in the treatment of claudication from FP disease. Industry has been reluctant to sponsor studies of nitinol stents due to logistical barriers.
VIVA Physician's, Inc. (VPI) analyzed subject-level data from the PTA control arm of three randomized FDA device trials conducted by industry. Subjects with Rutherford category 2-4 claudication and FP lesion lengths 4-15 cm with 12 month duplex ultrasound (DUS) assessment were identified. These data were combined with the results of a survey of the medical literature (1990-2006) for similar subjects.
Analysis of the industry derived control arm PTA data identified 116 patients (mean lesion length 8.7 cm) with a 12 month DUS defined FP patency of 28%. A similar cohort of 191 patients was identified from the medical literature in which the 12-month vessel patency equaled 37%; from these combined patient cohorts, expected vessel patency for PTA was estimated to equal 33%.
Based on the PTA performance efficacy rate of 33% derived from industry clinical trial data and the medical literature, and the requirement that the bare nitinol stent 12-month efficacy performance goal be set to equal twice this rate, the patency efficacy goal equals 66%. Additional information is provided on safety and other reporting standards and stent integrity evaluation for bare metal stents.