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Mortality in patients undergoing revascularization with paclitaxel eluting devices for infrainguinal peripheral artery disease: Insights from a network meta‐analysis of randomized trials
Abstract
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.
... Earlier NMAs in the field of EVT aimed to consolidate the results of these trials. However, some of them concentrated only on short-term but not long-term data over a period of 3 years [15][16][17]. Earlier studies in line with our results also reported the advantages of DCB and DES regarding revascularization [18]. ...
... It is also important to note that one study, published by Kuno et al. in 2020, discovered an excess mortality rate among patients treated with DES. This publication opened an ongoing discussion about mortality in patients with paclitaxel-eluting devices [17]. In terms of mortality, in line with the latest analyses, no statistically significant difference was observed among the different treatment groups in the full model analysis. ...
Background: Endovascular therapy offers an alternative for treating femoropopliteal (FP) and infrapopliteal (IP) lesions related to occlusive lower extremity artery disease. Despite numerous trials, the effectiveness of restenosis prevention using local drug delivery devices remains a topic of debate. Objectives: An updated systematic review and network meta-analysis was conducted. Our overall aim was to summarize the most recent clinical evidence regarding endovascular approaches for FP and IP atherosclerotic lesions. Methods: We conducted a search for randomized trials in the MEDLINE database, and extracted data related to clinical endpoints. Our primary focus was on the rate of major adverse events (MAEs), including mortality, amputation, and target lesion revascularization (TLR). A multiple treatment network meta-analysis supplemented with component network analyses was performed to examine the impact of combined treatment. Results: Our search yielded 33 randomized controlled trials encompassing 5766 patients. This included 19 studies focused on femoropopliteal and 14 on IP lesions, accounting for 3565 and 2201 patients, respectively. Drug-coated balloons (DCBs) and drug-eluting stents (DESs) displayed a reduced MAE risk in comparison to plain old balloon angioplasty (POBA)—RR for DCB: 0.64 (95% CI: 0.52–0.77) and for DES: 0.71 (95% CI: 0.51–0.99). The bare-metal stent (BMS) group manifested the most substantial MAE risk, being 59% higher relative to the DCB cohort (BMS vs. DCB RR: 1.59; 95% CI: 1.03–2.47). For FP lesions, DES was the standout performer, curtailing MAE risk by 55% relative to POBA. Within IP lesions, DES mitigated the MAE risk by 25% versus POBA. DCB did not exhibit any notable MAE reduction when pitted against POBA. Conclusion: In FP arteries, both DESs and DCBs yielded significantly diminished MAEs, thus outpacing other techniques. Regarding IP arteries, only DESs resulted in significantly fewer MAEs. In alignment with contemporary research, our findings revealed no signs of elevated mortality in patients undergoing treatment with drug-eluting apparatuses.
... The clinical trials confirmed the efficacy of PTX in reducing restenosis rates [6]. According to Kuno et al., PTX-eluting stents and balloons did not increase short-term mortality vs. balloon angioplasty [7]. PTX-eluting stents did not show a significant increase in long-term mortality vs. balloon angioplasty. ...
... Drug-coated devices are widely used for the treatment of peripheral artery disease. Recent studies demonstrate the advantages of using PTX-eluting stents compared to PTX-coated balloons [7,33]. It should be noted that the concentrations of PTX used for coating the balloons and commercially available PTX-eluting stents are an order of a magnitude higher than those used in the current study. ...
It was previously shown that polycaprolactone (PCL)-based electrospun-produced paclitaxel (PTX)-enriched matrices exhibit long-term drug release kinetics and can be used as coatings for drug-eluting stents (DES). The installation of vascular stents involves a twofold increase in stent diameter and, therefore, an elongation of the matrices covering the stents, as well as the arterial wall in a stented area. We studied the influence of matrix elongation on its structure and PTX release using three different electrospun-produced matrices. The data obtained demonstrate that matrix elongation during stent installation does not lead to fiber breaks and does not interfere with the kinetics of PTX release. To study PTX diffusion through the expanded artery wall, stents coated with 5%PCL/10%HSA/3%DMSO/PTX and containing tritium-labeled PTX were installed into the freshly obtained iliac artery of a rabbit. The PTX passing through the artery wall was quantified using a scintillator β-counter. The artery retained the PTX and decreased its release from the coating. The retention of PTX by the arterial wall was more efficient when incubated in blood plasma in comparison with PBS. The retention/accumulation of PTX by the arterial wall provides a prolonged drug release and allows for the reduction in the dose of the drugs in electrospun-produced stent coatings.
... It should be noted that poorly targeted drug delivery necessitates drug overdosing, which can induce subsequent undesired effects concerning non-drug-saving protocols. For example, paclitaxel-coated balloons showed a significant increase in long-term mortality compared to balloon angioplasty and bypass [6], which was apparently due to the high drug concentration released into the bloodstream. ...
To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery.
... Kuno et al. identified a total of 57 RCTs with 9362 patients. A comparison of seven different revascularization strategies returned no evidence of increased shortterm mortality after the use of coated balloons or stents or of increased longterm mortality after the use of coated stents; however, the use of paclitaxelcoated balloons was associated with increased long-term mortality [22]. Dinh et al. also investigated the association between mortality and paclitaxel-coated medical devices in patients with critical limb ischemia. ...
In 2018 and 2020, two meta-analyses using summary-level data from randomized controlled trials reported worse mortality following the application of paclitaxel-coated stents and balloons in femoropopliteal and crural arteries. These results initiated a heated global discussion concerning the validity of this association, while various observational studies using clinical and administrative registries proved the safety of coated devices. This article aimed to summarize the development and adoption of paclitaxel-coated balloons and stents for the treatment of peripheral arterial occlusive disease in clinical practice, research, and practice guidelines. It especially focusses on the European Unionʼs medical device regulation, which has far-reaching implications for the market approval and monitoring of high-risk medical devices.
In 2018 and 2020, two meta-analyses using summary-level data from randomized controlled trials reported worse mortality following the application of paclitaxel-coated stents and balloons in femoropopliteal and crural arteries. These results initiated a heated global discussion concerning the validity of this association, while various observational studies using clinical and administrative registries proved the safety of coated devices. This article aimed to summarize the development and adoption of paclitaxel-coated balloons and stents for the treatment of peripheral arterial occlusive disease in clinical practice, research, and practice guidelines. It especially focusses on the European Unionʼs medical device regulation, which has far-reaching implications for the market approval and monitoring of high-risk medical devices.
Background:
Endovascular treatment of occlusive disease of the superficial femoral artery (SFA) has evolved from plain old balloon angioplasty (POBA) through primary stenting strategy to drug eluting technology-based approach. The RAPID trial investigates the added value of drug coated balloons (DCB, Legflow) in a primary stenting strategy (Supera stent) for intermediate (5-15 cm) and long segment (>15 cm) SFA lesions.
Methods:
In this multicenter, patient-blinded trial, 160 patients with intermittent claudication, ischemic rest pain, or tissue loss due to intermediate or long SFA lesions were randomized (1:1) between Supera + DCB and Supera. Primary endpoint was primary patency at 2 years, defined as freedom from restenosis on duplex ultrasound (peak systolic velocity ratio < 2.4).
Results:
At 2 years, primary patency was 55.1% (95%CI: 43.1%-67.1%) in the Supera + DCB group versus 48.3% (95%CI: 35.6%-61.0%) in the Supera group (P=0.957). Per protocol analysis showed a primary patency rate of 60.9% (95%CI: 48.6%-73.2%) in the Supera + DCB group versus 49.8% (95%CI: 36.9%-62.7%) in the Supera group (P=0.469). The overall mortality rate was 5% in both groups (P=0.975). Sustained functional improvement was similar in both groups.
Conclusions:
The 2-year results in the current trial of a primary Supera stenting strategy are consistent with other trials reporting on treatment of intermediate and long SFA lesions. A DCB supported Supera stent strategy did not improve patency rate compared to a Supera stent only strategy.
Background:
A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients.
Methods:
We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling.
Results:
Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23).
Conclusions:
The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings.
Clinical trial registration:
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.
Purpose
The prospective randomized multicenter Freeway study evaluated the possible hemodynamic and clinical benefits of primary stent insertion followed by percutaneous transluminal angioplasty (PTA) with drug-eluting balloons (DEB) over post-stent insertion PTA with standard balloons in the treatment of symptomatic femoropopliteal arteriosclerotic lesions.
Methods
In total, 204 patients in 13 centers in Germany and Austria were enrolled and randomized to primary stenting followed by either FREEWAY™ drug-eluting balloon or standard PTA balloon angioplasty. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) at 6 months; the secondary endpoints include TLR rate at 12 months and primary patency, shift in Rutherford classification, ankle–brachial index (ABI) and major adverse events (MAE) at 6 and 12 months. Lesion characteristics and vessel patency were analyzed by an independent and blinded corelab.
Results
At 6-month and 12-month follow-up, TLR rate was lower in the DEB arm compared to standard PTA but did not reach statistical significance (4.1% vs. 9.0% p = 0.234 and 7.9% vs. 17.7% p = 0.064, respectively). Primary patency was significantly better for patients treated with the DEB at 6 months (90.3% vs. 69.8% p = 0.001) and 12 months (77.4% vs. 61.0% p = 0.027). Improvement in Rutherford classifications was likewise significantly better for patients in the DEB group at 6 (94.9% vs. 84.3% p = 0.027) and 12 months (95.5% vs. 79.9% p = 0.003). The percentage of patients with an improved ABI of 1.0–1.2 was significantly higher in the DEB group compared to the PTA group at 6 months (55.3% vs. 35.3%; p = 0.015) but without significant difference at 12 months (48.2% vs. 32.9%; p = 0.055). At 6 months, rate of major adverse events (MAE) was 1% in both arms, and at 12 months 2.2% for the DEB and 3.8% for the PTA group.
Conclusion
The Freeway Stent Study shows that the usage of DEB as a restenosis prophylaxis seems to be safe and feasible. The 12-month follow-up results give a clear sign in favor of the DEB group.
Background:
Drug-eluting technologies improve 12-month angiographic results of femoropopliteal (FP) interventions, but few data on the comparison between drug-coated balloons (DCBs) and drug-eluting stents (DES) are available.
Objectives:
The aim of this study was to compare, after balloon pre-dilation, a strategy of DCB followed by provisional self-expanding nitinol bare-metal stent implantation with a strategy of systematic DES implantation in patients at high risk for FP restenosis.
Methods:
Patients presenting with either intermittent claudication or critical limb ischemia undergoing FP intervention were randomly assigned 1:1 to DCB or DES after successful target lesion pre-dilation. The primary endpoint was 12-month target lesion binary restenosis, assessed using Doppler ultrasound. Secondary endpoints were freedom from target lesion revascularization and from major amputation.
Results:
A total of 192 patients, 96 in the DCB group and 96 in the DES group, with 240 lesions in 225 limbs, were included. Diabetes and critical limb ischemia were present in >50% in both groups. Mean lesion length was 14 cm, and baseline target lesion occlusion reached about 60% of cases in both groups. The systematic DES strategy yielded larger post-procedural minimal luminal diameter and a lower incidence of residual dissection compared to DCB, in which nitinol stents were used in only 21% of the lesions. Twelve-month target lesion restenosis was observed in 22% of DCB-treated versus 21% of DES-treated patients (p = 0.90). Clinically driven target lesion revascularization was necessary in 14% of DCB patients versus 17% of DES patients (p = 0.50).
Conclusions:
DCB was not superior to DES in the treatment of complex FP lesions in a high-risk population, yielding similar rate of restenosis and clinically driven target lesion revascularization. (Paclitaxel-Eluting Balloon Angioplasty With Provisional Use of Nitinol Stent Versus Systematic Implantation of Paclitaxel-Eluting Stent for the Treatment of Femoropopliteal De Novo Lesions; NCT01969630).
Background:
While randomized trials have demonstrated the superiority of drug-coated balloon (DCB) angioplasty versus standard percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal peripheral artery disease, the long-term durability of DCB angioplasty remains uncertain.
Methods and Results:
IN.PACT SFA is a prospective, multicenter, randomized single-blinded trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 subjects with symptomatic (Rutherford 2–4) femoropopliteal lesions. Subjects were randomly assigned 2:1 to the IN.PACT Admiral DCB or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, the primary safety end point, and major adverse events. Through 5 years, patients treated with the IN.PACT Admiral DCB demonstrated a sustained treatment effect with superior freedom from clinically driven target lesion revascularization when compared with PTA (Kaplan-Meier estimate of 74.5% versus 65.3%; log-rank P=0.020). The primary safety composite was achieved in 70.7% of subjects in the DCB and 59.6% in the PTA groups (P=0.068). The major adverse event rate was 42.9% for DCB and 48.1% for PTA (P=0.459). There were no device- or procedure-related deaths in either group as adjudicated by an independent and blinded Clinical Events Committee.
Conclusions:
The IN.PACT SFA randomized trial demonstrates that the IN.PACT Admiral DCB continues to perform better than PTA through 5 years with higher freedom from clinically driven target lesion revascularization. The sustained safety and effectiveness profile of this DCB supports its use as a preferred treatment choice compared with PTA for femoropopliteal lesions.
Objectives
To assess the longer‐term safety and efficacy of the IN.PACT Admiral (MDT‐2113) drug‐coated balloon (DCB) for the treatment of de novo and non‐stented restenotic lesions in the superficial femoral and/or proximal popliteal arteries versus uncoated percutaneous transluminal angioplasty (PTA) in a Japanese cohort.
Background
Although DCBs are the newest endovascular strategy for patients with peripheral artery disease presenting with femoropopliteal lesions, there remains a paucity of results in non‐Caucasian populations.
Methods
IN.PACT SFA Japan is an independently‐adjudicated, prospective, multicenter, randomized, single‐blinded trial. Endpoints through 2 years included primary patency and a composite safety endpoint of freedom from device‐ and procedure‐related death through 30 days, freedom from target limb major amputation and freedom from clinically‐driven target vessel revascularization at 24 months.
Results
One hundred patients were assigned by 2:1 randomization to treatment with the IN.PACT Admiral DCB (n = 68) or PTA (n = 32). The groups were well‐matched at baseline. Mean lesion length for the DCB and PTA groups were 9.15 ± 5.85 and 8.89 ± 6.01 cm (P = 0.838), respectively. Patients treated with DCB exhibited superior 24‐month primary patency compared to PTA (79.8% vs. 46.9%; log rank P < 0.001). The 24‐month clinically driven target lesion revascularization rate was 9.1% for DCB versus 20.7% for PTA (P = 0.177). There were no device‐ or procedure‐related deaths, major amputations, or thromboses in either group.
Conclusions
Two‐year results from IN.PACT SFA Japan demonstrated persistently superior patency and low CD‐TLR rates through 2 years when compared to uncoated PTA in Japanese patients. These data are consistent with other IN.PACT DCB trials.
Background:
Randomized trials of drug-eluting stents (DES) and drug-coated balloons (DCB) for femoropopliteal interventions reported superior patency rates for both strategies compared to standard balloon angioplasty. To date, head-to-head comparisons are missing.
Objectives:
The authors sought to compare DES versus DCB for femoropopliteal lesions through 36 months.
Methods:
Within a multicenter, randomized trial, 150 patients with symptomatic femoropopliteal disease were randomly assigned to primary DES implantation or DCB angioplasty with bailout stenting after stratification for lesion length (≤10 cm, >10 cm to ≤20 cm, and >20 cm to ≤30 cm). The primary effectiveness endpoint was primary patency at 12 months assessed by Kaplan-Meier. Secondary endpoints comprised major adverse events including death, major amputations, and clinically driven target lesion revascularization, and clinical outcomes.
Results:
More than one-half of lesions were total occlusions, and the stenting rate was 25.3% in the DCB group. Kaplan-Meier estimates of primary patency were 79% and 80% for DES and DCB at 12 months (p = 0.96) but decreased to 54% and 38% through 36 months (p = 0.17), respectively. Freedom from clinically driven target lesion revascularization was >90% at 12 months but dropped to around 70% at 36 months in both groups. Overall, the mortality rate through 36 months was 7.3%, with 1 procedure-related death in the DCB group. Improvement of clinical outcomes was sustained through 36 months.
Conclusions:
Patency rates at 12 months suggest comparable effectiveness and safety of DES versus DCB plus bailout stenting in femoropopliteal interventions; a trend in favor of the DES was observed up to 36 months. (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of the Femoropopliteal Artery [REAL PTX]; NCT01728441).
Background
Five years of prospective clinical trials confirm that the paclitaxel drug-coated balloon (DCB) (IN.PACT Admiral, Medtronic, Dublin, Ireland) is safe and effective to treat femoropopliteal artery disease. A recent meta-analysis of heterogeneous trials of paclitaxel-based balloons and stents reported that they are associated with increased mortality and that higher doses are linked to higher mortality from 2 to 5 years.
Objectives
The purpose of this study was to determine if there is a correlation between paclitaxel exposure and mortality by conducting an independent patient-level meta-analysis of 1,980 patients with up to 5-year follow-up.
Methods
Data from 2 single-arm and 2 randomized independently adjudicated prospective studies of a paclitaxel DCB (n = 1,837) and uncoated percutaneous transluminal angioplasty (PTA) (n = 143) were included. Analyses of baseline, procedure, and follow-up data of individual patients were performed to explore correlations of paclitaxel dose with long-term mortality. Survival time by paclitaxel dose tercile was analyzed with adjustment of inverse probability weighting to correct baseline imbalances and study as random effect. A standard cohort was defined to compare DCB- and PTA-treated patients with similar characteristics by applying criteria from pivotal studies (n = 712 DCB, n = 143 PTA).
Results
A survival analysis stratified nominal paclitaxel dose by low, mid, and upper terciles; mean doses were 5,019.0, 10,007.5, and 19,978.2 μg, respectively. Rates of freedom from all-cause mortality between the 3 groups through 5 years were 85.8%, 84.2%, and 88.2%, respectively (p = 0.731). There was no significant difference in all-cause mortality between DCB and PTA through 5 years comparing all patients (unadjusted p = 0.092) or patients with similar characteristics (adjusted p = 0.188).
Conclusions
This independent patient-level meta-analysis demonstrates that this paclitaxel DCB is safe. Within DCB patients, there was no correlation between level of paclitaxel exposure and mortality. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I], NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II], NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA], NCT01947478; The IN.PACT SFA Clinical Study for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery Using the IN.PACT Admiral™ Drug-Eluting Balloon in a Chinese Patient Population, NCT02118532; and IN.PACT Global Clinical Study, NCT01609296)
Background
Several randomized controlled trials (RCTs) have already shown that paclitaxel‐coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularization after lower extremity interventions.
Methods and Results
A systematic review and meta‐analysis of RCTs investigating paclitaxel‐coated devices in the femoral and/or popliteal arteries was performed. The primary safety measure was all‐cause patient death. Risk ratios and risk differences were pooled with a random effects model. In all, 28 RCTs with 4663 patients (89% intermittent claudication) were analyzed. All‐cause patient death at 1 year (28 RCTs with 4432 cases) was similar between paclitaxel‐coated devices and control arms (2.3% versus 2.3% crude risk of death; risk ratio, 1.08; 95% CI, 0.72–1.61). All‐cause death at 2 years (12 RCTs with 2316 cases) was significantly increased in the case of paclitaxel versus control (7.2% versus 3.8% crude risk of death; risk ratio, 1.68; 95% CI, 1.15–2.47; —number‐needed‐to‐harm, 29 patients [95% CI, 19–59]). All‐cause death up to 5 years (3 RCTs with 863 cases) increased further in the case of paclitaxel (14.7% versus 8.1% crude risk of death; risk ratio, 1.93; 95% CI, 1.27–2.93; —number‐needed‐to‐harm, 14 patients [95% CI, 9–32]). Meta‐regression showed a significant relationship between exposure to paclitaxel (dose‐time product) and absolute risk of death (0.4±0.1% excess risk of death per paclitaxel mg‐year; P<0.001). Trial sequential analysis excluded false‐positive findings with 99% certainty (2‐sided α, 1.0%).
Conclusions
There is increased risk of death following application of paclitaxel‐coated balloons and stents in the femoropopliteal artery of the lower limbs. Further investigations are urgently warranted.
Clinical Trial Registration
URL: www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42018099447.
Background:
New-generation bare-metal nitinol (BNS) and drug-eluting stents have improved long-term outcomes in patients undergoing endovascular therapy for femoropopliteal lesions. Furthermore, cilostazol reduces in-stent restenosis (ISR) after first-generation BNS implantation for femoropopliteal lesions.
Methods and results:
We studied 255 patients with femoropopliteal lesions treated at 25 cardiovascular centers. Patients were randomly assigned to the BNS group (Misago stent implantation without cilostazol), BNS with cilostazol group (Misago stent implantation with cilostazol), or drug-eluting stents group (Zilver PTX stent implantation without cilostazol). Primary end point was 1-year restenosis noted using duplex ultrasound (peak systolic velocity ratio, >2.0). Secondary end point was major adverse limb events (limb-related death, target lesion revascularization, major amputation, and major bleeding). During the 1-year follow-up, 12 patients (4.7%) died and 237 (92.9%) had relevant ultrasound findings. The 1-year ISR rate did not differ significantly among the BNS, BNS with cilostazol, and drug-eluting stents groups (28.4% versus 12.2% versus 21.0%; P=0.052). Although the 1-year ISR rate was significantly lower in the BNS with cilostazol group than in the BNS group, it was similar to that in the drug-eluting stents group ( P=0.16). Major adverse limb event was significantly higher in the BNS group (16.9% versus 6.5% versus 6.3%; P=0.034); however, target lesion revascularization and major bleeding were similar (9.7% versus 5.1% versus 3.6%; P=0.25, 4.8% versus 1.2% versus 2.4%; P=0.37, respectively).
Conclusions:
Misago stent implantation with cilostazol showed a comparable 1-year ISR rate with Zilver PTX. Cilostazol reduced the 1-year ISR rate after endovascular therapy when used with new-generation BNS.
Clinical trial registration:
URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN 000010071.
Objectives:
The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months.
Background:
Drug-coated balloons (DCBs) are a promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study.
Methods:
The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68 ± 8 years, 53 men) were enrolled in the Ranger DCB arm, and 34 patients (mean age 67 ± 9 years, 23 men) were assigned to the control group. Twelve-month analysis included patency, safety, and clinical outcomes and quality-of-life assessments.
Results:
The DCB group had a greater primary patency rate at 12 months (Kaplan-Meier estimate 86.4% vs. 56.5%), with a significantly longer time to patency failure (log-rank p < 0.001). The estimated freedom from target lesion revascularization rate was 91.2% in the DCB group and 69.9% in the control group at 12 months, with a significantly longer time to reintervention (p = 0.010). No target limb amputations or device-related deaths occurred in either group.
Conclusions:
Twelve-month results show that patency was maintained longer after Ranger DCB treatment than after conventional balloon angioplasty, and this result was associated with a low revascularization rate and good clinical outcomes.
Purpose:
The previously reported 6-month angiographic and 12-month clinical outcomes of the CONSEQUENT trial demonstrated the safety and efficacy of a novel paclitaxel-resveratrol-coated balloon for the treatment of lesions in the femoropopliteal segment. The purpose of this report is to present the 2-year results including a cost-benefit analysis for Germany.
Materials and methods:
Patients with symptomatic peripheral artery occlusive disease in femoropopliteal lesions were randomized either to drug-coated balloon (DCB, n = 78) or plain old balloon angioplasty (POBA, n = 75). As secondary endpoints, the 2-year clinical results consisting of target lesion revascularization (TLR), patency and increase in walking distance were recorded. Based on the Kaplan-Meier analyses for TLR and other adverse events, a cost-benefit analysis was conducted for the German DRG system.
Results:
There were no additional TLRs in both groups between 14 and 24 months so that the corresponding rates remained significantly different between the treatment groups (DCB: 19.1 vs. POBA 40.6%, p = 0.007). At 2 years, the patency rate was significantly higher in the DCB group (72.3 vs. 48.4%, p = 0.006). The walking distance increase was also significantly higher after DCB angioplasty (172 ± 103 vs. 52 ± 136 m, p = 0.001). We estimated 2-year cost savings of € 1111.97 per patient treated with DCB instead of POBA.
Conclusions:
The use of paclitaxel-resveratrol matrix-coated peripheral balloons compared to POBA was associated with a significantly reduced TLR rate, superior patency and substantial cost savings at 2 years. ClinicalTrials.gov Identifier NCT01970579.
Purpose:
To assess the safety and effectiveness of the MDT-2113 (IN.PACT Admiral) drug-coated balloon (DCB) for the treatment of de novo and native artery restenotic lesions in the superficial femoral and proximal popliteal arteries vs percutaneous transluminal angioplasty (PTA) with an uncoated balloon in a Japanese cohort.
Methods:
MDT-2113 SFA Japan ( ClinicalTrials.gov identifier NCT01947478) is an independently adjudicated, prospective, randomized, single-blinded trial that randomized (2:1) 100 patients (mean age 73.6±7.0 years; 76 men) from 11 Japanese centers to treatment with DCB (n=68) or PTA (n=32). Baseline characteristics were similar between the groups, including mean lesion length (9.15±5.85 and 8.89±6.01 cm for the DCB and PTA groups, respectively). The primary effectiveness outcome was primary patency at 12 months, defined as freedom from clinically-driven target lesion revascularization (CD-TLR) and freedom from restenosis as determined by duplex ultrasonography. The safety endpoint was a composite of 30-day device- and procedure-related death and target limb major amputation and clinically-driven target vessel revascularization within 12 months.
Results:
Patients treated with DCBs exhibited superior 12-month primary patency (89%) compared to patients treated with PTA (48%, p<0.001). The 12-month CD-TLR rate was 3% for DCB vs 19% for PTA (p=0.012). There were no device- or procedure-related deaths, major amputations, or thromboses in either group. Quality-of-life measures showed sustained improvement from baseline to 12 months in both groups.
Conclusion:
Results from the MDT-2113 SFA Japan trial showed superior treatment effect for DCB vs PTA, with excellent patency and low CD-TLR rates. These results are consistent with other IN.PACT SFA DCB trials and demonstrate the safety and effectiveness of this DCB for the treatment of femoropopliteal lesions in this Japanese cohort.
Objectives
This study sought to compare heparin-bonded endografts with femoropopliteal bypass, including quality of life, using general health and disease-specific questionnaires as well as patency rates.
Background
Endovascular treatment continues to advance and is gaining acceptance as primary treatment for long occlusive or stenotic lesions in the superficial femoral artery. Heparin-bonded expanded polytetrafluoroethylene endografts have been related to outcomes comparable to bypass surgery, but this has not been tested in a randomized fashion.
Methods
A multicenter randomized-controlled trial was performed comparing femoropopliteal bypass with heparin-bonded expanded polytetrafluoroethylene endografts. Data were analyzed on an intention-to-treat and per-protocol manner.
Results
A total of 129 patients were randomized and 125 patients were treated, 63 in the endoluminal and 62 in the surgical group (42 venous, 20 prosthetic). Enrollment was terminated before reaching the predefined target number for patency. Baseline characteristics and anatomical data were similar. Patients were treated for critical limb ischemia in 38.1% and 32.2% in the endoluminal and surgical arms, respectively. Mean lesion length was 23 cm in both groups and lesions were largely TransAtlantic Inter-Society Consensus II D. Hospitalization time and 30-day morbidity were significantly lower in the endoluminal group, without differences in serious adverse events (n = 5 each; surgical: 4 venous and 1 polytetrafluoroethylene bypass). There were no significant differences in Rutherford category between groups at any time point. At 30 days the endoluminal group showed a greater improvement in quality-of-life scores. At 1 year, these differences had largely disappeared and no differences in primary (endoluminal: 64.8%; surgical: 63.6%), assisted primary (endoluminal: 78.1%; surgical: 79.8%), secondary patency (endoluminal: 85.9%; surgical: 83.3%), and target vessel revascularization (endoluminal: 72.1%; surgical: 71.0%) were observed. Limb salvage rate was 100% in both groups.
Conclusions
Heparin-bonded endoluminal bypass for long segment lesions shows promising results (less morbidity, faster recovery, and improvement in quality of life with indistinguishable patency rates at 1 year) compared with surgical bypass. Long-term results have to be awaited.
Purpose: We used randomized trials of radiotherapy (RT) with or without chemotherapy in non-metastatic nasopharyngeal carcinoma to investigate the survival benefit of chemoradiotherapy regimens between two/three-dimensional radiotherapy (2D/3D RT) and intensity-modulated radiotherapy (IMRT).
Methods: Overall, 27 trials and 7,940 patients were included. Treatments were grouped into seven categories including RT alone, induction chemotherapy (IC) followed by RT (IC-RT), RT followed by adjuvant chemotherapy (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concurrent chemo-radiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). To distinguish between 2D/3D RT and IMRT, three categories in IMRT were newly added, including CRT in IMRT, IC-CRT in IMRT, and CRT-AC in IMRT. The P score was used to rank the treatments.
Results: Both fixed- and random-effects frequentist and Bayesian network meta-analysis models were applied, which provided similar results and the same ranking. IC-CRT was the most effective regimen compared with CRT-AC and CRT in the IMRT era for overall survival (OS) (HR, 95% CI, IC-CRT vs. CRT-AC, 0.61 (0.45, 0.82); IC-CRT vs. CRT 0.65 (0.47, 0.91)), progression-free survival (PFS) (0.69 (0.54, 0.88); 0.63 (0.49, 0.80)), and distant metastasis-free survival (DMFS) (0.58 (0.28, 1.21); 0.60 (0.42, 0.85)). CRT-AC achieved the highest survival benefit compared with CRT, and IC-CRT for loco-regional relapse-free survival (LRRFS) (0.44 (0.15, 1.28); 0.72 (0.22, 2.33)). Among these 10 categories, after distinguishing between 2D/3D RT and IMRT, IC-CRT in IMRT ranked first for OS, PFS, and DMFS, and CRT-AC in IMRT ranked first for LRRFS.
Conclusion: IC-CRT should be the most suitable regimen for loco-regionally advanced NPC in the IMRT era.
Background
Clinical outcomes reported after treatment of infrapopliteal lesions with drug‐eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (PTA‐BMS) through midterm follow‐up in patients with critical limb ischemia. In the present study, long‐term results of treatment of infrapopliteal lesions with DESs are presented.
Methods and Results
Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA‐BMS or DESs with paclitaxel. Long‐term follow‐up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with DESs and 66 limbs (64 patients) were treated with PTA‐BMS. The estimated 5‐year major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA‐BMS; P=0.091). The 5‐year rates of amputation‐ and event‐free survival (survival free from major amputation or reintervention) were significantly higher in the DES arm compared with PTA‐BMS (31.8% versus 20.4%, P=0.043; and 26.2% versus 15.3%, P=0.041, respectively). Survival rates were comparable. The limited available morphological results showed higher preserved patency rates after DESs than after PTA‐BMS at 1, 3, and 4 years of follow‐up.
Conclusions
Both clinical and morphological long‐term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA‐BMS.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.
Background
Paclitaxel‐eluting balloon (PEB) angioplasty has superior efficacy compared with conventional balloon angioplasty (BA) for de novo lesions of superficial femoral artery (SFA). Studies investigating the angiographic and clinical performance of PEB angioplasty versus BA for in‐stent restenosis of SFA are limited. We performed a randomized trial to investigate angiographic and clinical performance of PEB versus BA for in‐stent restenosis of SFA.
Methods and Results
Patients with symptomatic in‐stent restenosis of SFA were randomly assigned to either PEB or BA at 2 centers in Munich, Germany. The primary end point was the percentage diameter stenosis at 6‐ to 8‐month follow‐up angiography. Secondary end points were the rate of binary restenosis at follow‐up angiography and target lesion revascularization, target vessel thrombosis, ipsilateral amputation, bypass surgery of the affected limb, and all‐cause mortality at 24‐month follow‐up. Seventy patients were assigned to PEB (n=36) or BA (n=34). Mean lesion length was 139±67 mm, and roughly one third of lesions were completely occluded at the time of the index procedure. At control angiography, the percentage diameter stenosis (44±33% versus 65±33%, P=0.01) and binary restenosis were significantly reduced with PEB versus BA (30% versus 59%, P=0.03). At 24‐month follow‐up, PEB was associated with a significant reduction of target lesion revascularization in comparison to BA (19% versus 50%, P=0.007). There was no difference with respect to other outcomes of interest.
Conclusions
In patients with in‐stent restenosis of SFA, a percutaneous therapy with PEB compared with BA has superior angiographic performance at 6 to 8 months and improved clinical efficacy up to 24‐month follow‐up.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01083394.
Background:
Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease.
Methods:
In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable.
Results:
In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL).
Conclusions:
The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour.
Clinical trial registration:
URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.
Objectives
The TECCO (Traitement des Lésions Athéromateuses de l’Artère Fémorale Commune par Technique Endovasculaire Versus Chirurgie Ouverte [Endovascular Versus Open Repair of the Common Femoral Artery]) trial is a randomized comparison of safety and efficacy of stenting versus open surgery for de novo common femoral artery (CFA) stenosis.
Background
Surgery for CFA lesions is considered effective and durable. Despite the widespread use of endovascular repair for infrainguinal disease, the value of this procedure for such lesions is uncertain.
Methods
From February 23, 2011, to September 5, 2013, a total of 117 patients with de novo atherosclerotic lesions of the CFA were randomly assigned to undergo surgery (n = 61) or stenting (n = 56). The main exclusion criteria were asymptomatic disease, restenosis, and thrombosis of the CFA. The primary outcome was the morbidity and mortality rate within 30 days. This includes any general complications or local complications that caused or prolonged hospitalization and/or re-intervention, lymphorrhea of more than 3 days, and post-operative paresthesia that required drugs. The median duration of follow-up was 2 years (interquartile range [IQR]: 19.8 to 24.9 years).
Results
Primary outcome events occurred in 16 of 61 patients (26%) in the surgery group and 7 of 56 patients (12.5%) in the stenting group (odds ratio: 2.5; 95% confidence interval: 0.9 to 6.6; p = 0.05). The mean duration of hospitalization was significantly lower in the stenting group (3.2 ± 2.9 days vs. 6.3 ± 3 days; p < 0.0001). At 24 months, the sustained clinical improvement, the primary patency rate, and the target lesion and extremity revascularization rates were not different in the 2 groups.
Conclusions
In patients with de novo atherosclerotic lesions of the CFA, the perioperative morbidity and mortality rate was significantly lower among patients who underwent endovascular therapy by stenting compared with surgery, whereas clinical, morphological, and hemodynamic outcomes were comparable at mid-term. (Traitement des Lésions Athéromateuses de l’Artère Fémorale Commune par Technique Endovasculaire Versus Chirurgie Ouverte [Endovascular Versus Open Repair of the Common Femoral Artery] [TECCO]; NCT01353651)
Objectives:
Based on a novel paclitaxel-resveratrol drug matrix, the safety and efficacy to inhibit intimal hyperplasia were studied in symptomatic claudicants with morphologically challenging lesions.
Background:
The treatment of peripheral artery occlusive disease (PAOD) with percutaneous transluminal angioplasty is limited by occurrence of vessel recoil and neointimal hyperplasia. Drug-coated balloons (DCB) deliver drugs to the arterial wall to potentially reduce the restenosis rate. A number of paclitaxel-coated balloon technologies are available to treat peripheral lesions.
Methods:
In this randomized controlled trial, a total of 153 patients with symptomatic PAOD in femoro-popliteal lesions were randomized either to DCB or plain old balloon angioplasty (POBA).
Results:
The mean lesion length was 13.2 ± 10.4 cm with target lesion total occlusions in 26.1% of all patients (40/153). The primary endpoint of in-lesion late lumen loss (LLL) at 6 months was significantly reduced in the DCB group as compared to the POBA group (0.35 mm CI [0.19; 0.79 mm] vs. 0.72 mm CI [0.68; 1.22 mm], p = 0.006). At 12 months, the TLR rate in the DCB group was significantly lower as compared to the POBA group (17.8 vs. 37.7% p = 0.008). The censored walking distance increase suggests a benefit for patients who underwent DCB angioplasty as compared to the standard POBA treatment (12 months 165 ± 105 vs. 94 ± 136 m, p = 0.012).
Conclusion:
The use of paclitaxel-resveratrol-matrix-coated peripheral balloon angioplasty as compared to POBA was associated with significantly reduced in-lesion LLL and reduced TLR rates. ClinicalTrials.gov identifier NCT01970579.
Background
Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries. However, the treatment effect compared with an uncoated balloon has differed greatly among the randomized trials, with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low-dose (2-µg/mm² surface dose of paclitaxel) DCB.
Methods
This was a prospective, randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty (PTA) balloon. The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months after the procedure. The primary effectiveness end point was primary patency at 12 months.
Results
Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation. Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented total occlusions, respectively. The primary safety end point was met, and superiority was demonstrated; freedom from a primary safety event was 94.1% (193 of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95% confidence interval, 0.9%–23.0%). The primary effectiveness end point was met, and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40 of 66]; P<0.001). Outcomes with DCB were also superior to PTA per the Kaplan-Meier estimate for primary patency (89.0% versus 65.0% at 365 days; log-rank P<0.001) and for rates of clinically driven target lesion revascularization (5.9% versus 16.7%; P=0.014).
Conclusions
Superiority with a low-dose DCB for femoropopliteal interventions was demonstrated over PTA for both the safety and effectiveness end points.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01858363.
Background:
Atherosclerosis in the superficial femoral artery is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting, and directional atherectomy (DA) have provided new options for the treatment of superficial femoral artery disease; however, the comparative efficacy of these interventional strategies remains uncertain.
Methods:
One hundred and fifty-five patients with symptomatic peripheral artery disease due to de novo superficial femoral artery stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA and stenting (n=52), or DA with distal protection and bailout stenting (n=55). The primary end point of the study was percentage diameter stenosis after 6 months measured by angiography. Other end points included target lesion revascularization, thrombosis, ipsilateral amputation, binary restenosis, and all-cause mortality at 6 and 24 months.
Results:
Baseline and lesion characteristics were comparable in all groups with a mean lesion length of 65.9±46.8 mm and 56% total occlusions. At 6 months angiography, the percent diameter stenosis was significantly lower in patients treated by PEB angioplasty and stenting (34±31%) as compared with BA angioplasty and stenting (56±29%, P=0.009) or DA (55±29%, P=0.007). Similarly, binary restenosis was significantly lower after treatment with PEB and stenting as compared with BA and stenting or DA. Clinical follow-up at 24 months revealed a lower risk for target lesion revascularization after PEB angioplasty and stenting as compared with BA and stenting or DA. We found no difference in terms of target lesion thrombosis and mortality among groups, and no patient underwent amputation.
Conclusions:
Treatment of de novo superficial femoral artery lesions with PEB angioplasty and stenting is superior to BA angioplasty and stenting or DA in terms of angiographic diameter stenosis at 6 months and target lesion revascularization at 24 months.
Clinical trial registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00986752.
Background—
Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions.
Methods and Results—
Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia–related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03).
Conclusions—
In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.
Background:
-This randomized controlled trial (RCT) evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA); overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]); and provisional DES versus provisional BMS.
Methods and results:
-Patients with symptomatic femoropopliteal artery disease were randomized to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary endpoints of event-free survival and patency showed superiority of primary DES compared to PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, p<0.01), patency (66.4% versus 43.4%, p<0.01), and freedom from reintervention (TLR, 83.1% versus 67.6%, p<0.01) for the overall DES group were superior to standard care in non-randomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, p=0.02), patency (72.4% versus 53.0%, p=0.03), and freedom from TLR (84.9% versus 71.6%, p=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and TLR through 5 years for the overall DES compared to standard care and provisional DES compared to provisional BMS.
Conclusions:
-The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability compared to standard endovascular treatments. Clinical Trial Registration Information-www.clinicaltrials.gov. Identifier: NCT00120406.
This chapter describes the principles and methods used to carry out a meta-analysis for a comparison of two interventions for the main types of data encountered. A very common and simple version of the meta-analysis procedure is commonly referred to as the inverse-variance method. This approach is implemented in its most basic form in RevMan, and is used behind the scenes in many meta-analyses of both dichotomous and continuous data. Results may be expressed as count data when each participant may experience an event, and may experience it more than once. Count data may be analysed using methods for dichotomous data if the counts are dichotomized for each individual, continuous data and time-to-event data, as well as being analysed as rate data. Prediction intervals from random-effects meta-analyses are a useful device for presenting the extent of between-study variation. Sensitivity analyses should be used to examine whether overall findings are robust to potentially influential decisions.
Background Paclitaxel drug-coated balloon (DCB) catheter angioplasty is the preferred treatment for revascularization of femoropopliteal lesions in peripheral artery disease, but mortality is a safety concern. Purpose To assess 2-year efficacy and safety of DCB angioplasty compared with conventional balloon angioplasty (also known as plain old balloon angioplasty or POBA). Materials and Methods This prospective, multicenter, randomized controlled trial enrolled consecutive participants with symptomatic superficial femoral and/or popliteal artery disease at 11 German centers between September 2015 and December 2016. Participants underwent DCB angioplasty or conventional balloon angioplasty. Primary outcome of 6-month late lumen loss showed superiority of DCB angioplasty over conventional balloon angioplasty. Evaluation at 2 years included secondary outcomes of primary patency and target lesion revascularization (TLR) estimated with Kaplan-Meier analysis, clinical and hemodynamic improvement, quality of life, target limb amputation, and all-cause mortality. Results A total of 171 participants (mean age, 69 years ± 8; 111 men) were evaluated. At 2 years, primary patency was achieved in 90.2% (95% confidence interval [CI]: 80.4%, 95.2%) of DCB angioplasty and 62.7% (95% CI: 50.0%, 73.0%) of conventional balloon angioplasty participants (P < .001). Freedom from TLR occurred in 97.2% (95% CI: 89.1%, 99.3%) of DCB angioplasty and 78% (95% CI: 66.5%, 86.0%) of conventional balloon angioplasty participants (P = .001). The groups did not differ in sustained improvement from baseline to 2 years in Rutherford-Becker category (row mean scores difference, 1.7; P = .19) and showed no difference in mean improvement in the Walking Impairment Questionnaire score (-0.8%; 95% CI: -11.8%, 10.2%; P = .88), EuroQol Group's five-dimension index of quality of life (-0.06; 95% CI: -0.17, 0.03; P = .20), or ankle-brachial index (0.03; 95% CI: -0.08, 0.14; P = .57). No major amputation was necessary. One DCB angioplasty and two conventional balloon angioplasty participants died (risk ratio, 0.48; 95% CI: 0.04, 5.10). Conclusion At 2 years after paclitaxel drug-coated balloon (DCB) angioplasty, primary patency and freedom from target lesion revascularization remained superior compared with conventional balloon angioplasty. DCB angioplasty resulted in sustained clinical and hemodynamic improvement with no increased risk of mortality. © RSNA, 2020 Online supplemental material in available for this article.
Objectives:
The primary objective of the BATTLE (Bare Metal Stent vs. Paclitaxel Eluting Stent in the Setting of Primary Stenting of Intermediate-Length Femoropopliteal Lesions) trial is to demonstrate the clinical superiority of the Zilver PTX stent over the Misago stent in the treatment of femoropopliteal lesions.
Background:
No randomized studies have compared self-expanding paclitaxel-eluting stents with bare-metal stents in the treatment of femoropopliteal lesions.
Methods:
BATTLE is a multicenter randomized controlled trial in patients with symptomatic (Rutherford category 2 to 5) de novo lesions of the superficial femoral or proximal popliteal artery. The primary endpoint is freedom from in-stent restenosis (ISR) at 1 year, with restenosis defined as a peak systolic velocity index >2.4 at the target lesion. The Kaplan-Meier method was used to evaluate time-to-event data for freedom from ISR over the 2-year follow-up period.
Results:
Between March 2014 and August 2016, 186 patients were enrolled; 91 were assigned to the Misago arm and 90 to the Zilver PTX arm. Kaplan-Meier 1-year estimates of freedom from ISR were 88.6% for Misago and 91% for Zilver PTX (hazard ratio [HR]: 1.2; 95% confidence interval [CI]: 0.6 to 2.4; p = 0.64). Comparing Misago with Zilver PTX, 2-year estimates were 6.4% and 1.2% (HR: 7.3; 95% CI: 0.9 to 59.3; p = 0.0632) for mortality, 74.6% and 78.8% (HR: 1.2; 95% CI: 0.6 to 2.1; p = 0.62) for patency, and 14.4% and 12.4% (HR: 1.2; 95% CI: 0.5 to 2.8; p = 0.69) for target lesion revascularization.
Conclusions:
In the treatment of symptomatic femoropopliteal lesions, the Zilver PTX stent failed to show superiority over the Misago stent in freedom from ISR at 1 year.
Purpose: To report the 12-month results of a multicenter, prospective, randomized controlled trial to determine if the ZILVER PTX paclitaxel-eluting stent was noninferior in terms of safety and efficacy compared with surgical bypass. Materials and Methods: This is a study in symptomatic TransAtlantic Inter-Society Consensus (TASC) C and D femoropopliteal lesions comparing endovascular ZILVER PTX stenting vs surgical bypass surgery using a prosthetic graft ( ClinicalTrials.gov identifier NCT01952457). Between October 2013 and July 2017, 220 patients (mean age 68.6±10.5 years; 159 men) were enrolled and randomized to the ZILVER PTX treatment group (113, 51.4%) or the bypass treatment group (107, 48.6%). Most of the lesions were occlusions (208, 94.5%); the mean lesion length was 247.1±69.3 mm. The primary outcome measure was primary patency at 12 months, defined as no evidence of binary restenosis or occlusion within the target lesion or bypass graft based on a duplex-derived peak systolic velocity ratio <2.4 and no clinically-driven target lesion revascularization (TLR) in endovascular cases or reintervention to restore flow in the bypass. Results: The estimated 12-month primary patency rate was 74.5% (95% CI 66.3% to 82.7%) for the ZILVER PTX group vs 72.5% (95% CI 63.7% to 81.3%) for the bypass arm (p=0.998). Freedom from TLR at 12 months was 80.9% (95% CI 73.3% to 88.5%) for the ZILVER PTX group vs 76.2% (95% CI 68.0% to 84.4%) for the bypass group (p=0.471). The 30-day complication rate was significantly lower in the ZILVER PTX group (4.4% vs 11.3%, p=0.004). Also, procedure time and hospital stay were significantly shorter in the ZILVER PTX group (p<0.001 for both). Conclusion: With noninferior patency results, a lower complication rate, and shorter procedures and hospital stays, paclitaxel-eluting stenting might become a recommended treatment for long TASC C and D femoropopliteal lesions.
Aims:
Although paclitaxel drug-coated balloon (DCB) angioplasty is an established endovascular treatment for peripheral artery disease, restenosis remains a major concern. Thus, we compared a novel paclitaxel-coated DCB with nano-coating technology with uncoated plain-old balloon angioplasty (POBA).
Methods and results:
This multicenter trial randomly assigned 171 patients with stenotic and occlusive lesions of the femoropopliteal artery to angioplasty with the novel DCB or uncoated POBA. The primary endpoint late lumen loss at 6 months was 0.92 mm lower in the DCB group (95%CI: -1.36 mm; -0.49 mm, P<0.001). Patients showed improved walking after DCB treatment at 6 months (P=0.021). In the DCB group, 44.6%/50% of the patients improved by three Rutherford-Becker classification stages after 6/12 months (POBA: 27.8%/36.8%). Only one patient needed TLR (1.3%) in the DCB group, compared to 14 (18.7%) in the POBA group after 12 months (relative risk [RR]=0.08, 95%CI: 0.01; 0.53, P<0.001). Primary patency was 90.3% (DCB group) vs. 65.3% (POBA group) after 12 months (RR=1.38, 95%CI: 1.14; 1.67, P<0.001).
Conclusions:
The novel DCB was effective and safe for inhibiting restenosis. Moreover, it demonstrated a better improvement in walking than POBA and showed no mortality concerns due to paclitaxel application after 12 months.
Objectives:
We hypothesized that a drug-coated balloon (DCB) could improve treatment efficacy while maintaining safety when compared with percutaneous transluminal angioplasty (PTA) for the treatment of atherosclerotic infrapopliteal arterial lesions.
Methods:
A total of 442 patients with angiographically significant lesions were randomized (2:1) to DCB or PTA. The primary safety and efficacy endpoints were freedom from major adverse limb events and perioperative death (MALE-POD) at 30 days, and freedom from vessel occlusion, clinically driven target-lesion revascularization (CD-TLR), and above-ankle amputation measured at 6 months. Success was achieved if safety between groups was non-inferior (margin 12%), and efficacy was statistically significant either for the overall intention-to treat (ITT) or the proximal-segment DCB groups (ie, the proximal two-thirds of the below-knee arterial pathways).
Results:
Freedom from MALE-POD for the DCB group (99.3%) was non-inferior to PTA (99.4%; non-inferiority P<.001). Proportional analysis of the primary efficacy endpoint was statistically significant for the proximal-segment DCB group (76%) vs PTA (62.9%; one-sided P<.01; Bayesian P-value for success of .0085) while not statistically significant for the overall ITT group (74.5% for DCB vs 63.5% for PTA; one-sided P=.02). Kaplan-Meier analyses demonstrated superior efficacy for DCB in both the overall ITT and proximal-segment groups at 6 months. Primary patency and CD-TLR, hypothesis-tested secondary endpoints, were also statistically better for the DCB group compared with PTA at 6 months (one-sided P<.025).
Conclusions:
DCB treatment for symptomatic infrapopliteal arterial lesions produced non-inferior safety at 30 days and a statistically significant difference in the primary efficacy endpoint when compared with PTA at 6 months.
Purpose:
To assess the efficacy and safety of Orchid drug-coated balloon (DCB) for treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) in Chinese patients.
Methods:
The study is a prospective, single center, single-blinded, randomized controlled trial (RCT) that randomized (1:1) 74 patients to DCB group (n=38) and PTA group (n=36). The primary efficacy endpoint was primary patency of the target lesion at 12 months. Second efficacy endpoint included clinically-driven target-lesion revascularization (CD-TLR) and ABI change at 12 months. The primary safety endpoint included peri-operative death at 30 days, all-cause death, major amputation, and other major adverse events (MAEs) at 12 months. The primary functional endpoint included Walking Impairment Questionnaire (WIQ), quality-of-life measures (EQ-5D) and 6-minute walking test (6MWT).
Results:
The DCB group had higher primary patency (87.9% vs. 51.6%; P=0.001) and lower rates of CD-TLR (6.1% vs. 35.5%; P=0.003) than the PTA groupat 12 months. There were no peri-operative deaths, and no major amputations at 12 months in two groups. There were 1(2.6%) in the DCB group and 2(5.6%) in the PTA group of all-cause deaths(P=0.524).
Conclusions:
Results from the study showed superior treatment effect with Orchid DCB versus PTA for the treatment of FP ISR, and without an apparent difference in safety.
To determine whether statin (hydroxymethylglutaryl-CoA reductase inhibitor) therapy is associated with better midterm survival after transcatheter aortic valve implantation (TAVI), the first meta-analysis of currently available studies was performed. To identify all observational comparative studies and randomized controlled trials (RCTs) of statin versus control (no statin) therapy or cohort studies investigating statin treatment as one of covariates in patients undergoing TAVI, PubMed, Web of Science, and Google Scholar were searched through March 2019. Adjusted (if unavailable, unadjusted) hazard ratios (HRs) with their confidence interval (CIs) of midterm (≥1 year) all-cause mortality after TAVI for statin therapy were extracted from each study. Study-specific estimates were combined by means of inverse variance-weighted averages of logarithmic HRs in the random-effects model. Eight eligible studies with a total of 5,170 TAVI patients were identified and included in the present meta-analysis. The primary meta-analysis (including HRs for high intensity statin from 3 studies together with other HRs) demonstrated that statin treatment was associated with significantly lower midterm mortality (HR, 0.74; 95% CI, 0.60 to 0.91; p = 0.005). The secondary meta-analysis (including HRs for low/moderate intensity statin from 3 studies together with other HRs) also indicated an association of statin therapy with significantly lower midterm mortality (HR, 0.80; 95% CI, 0.69 to 0.93; p = 0.005). No funnel plot asymmetry for the primary meta-analysis (p = 0.64) was identified, which suggested probably no publication bias. In conclusion, statin therapy is associated with better midterm survival after TAVI.
Objectives:
The authors sought to investigate the midterm efficacy and safety of drug-coated balloon (DCB) in the treatment of severe femoropopliteal artery disease (FPAD).
Background:
The midterm outcome of DCB versus uncoated balloon percutaneous transluminal angioplasty (PTA) for FPAD are still debated.
Methods:
A total of 200 Chinese patients with FPAD were prospectively randomized into treatment with DCB or with PTA. The primary efficacy endpoints were primary patency of the target lesion, freedom from clinically driven target lesion revascularization, improved ankle-brachial index, and improved Rutherford class at 24 months. The primary safety endpoint was the rate of major adverse events.
Results:
The DCB group and PTA group were comparable in demographic characteristics and clinical severity at baseline. At 24-month follow-up, primary patency was better in the DCB group versus PTA group (64.6% vs. 31.4%; p < 0.001). The DCB group had a higher rate of freedom from clinically driven target lesion revascularization than the PTA group (86.5% vs. 58.9%; p < 0.001). Rutherford class and ankle-brachial index also confirmed more improvements in the DCB group (p < 0.01 and p < 0.05, respectively). There was no significant difference in major adverse events.
Conclusions:
The superiority of DCB versus PTA in the efficacy of FPAD treatment persists at 24-month follow-up and the safety of DCB is equivalent to that of PTA.
Introduction:
Claudication and critical limb threatening ischemia (CLTI) are significant causes of mortality in the elderly. The gold standard of superficial femoral artery (SFA) revascularization is thus far considered to be the femoropopliteal bypass. The aim of this study was to compare mid-term patency between drug-eluting stents (DES) and prosthetic bypass grafts (BSX). Studies have reported comparable results for both methods.
Materials and methods:
46 patients with claudication or rest pain due to a 5-25 cm SFA-occlusion were randomized between DES and BSX. Follow-up was 24 months, and the primary outcome measure was overall patency. Secondary outcome measures were primary and primary assisted patency, change in ankle-brachial index (ABI), as well as amputation-free survival.
Results:
41 patients were eventually analyzed. 6 month secondary patency was 91 % (DES) vs. 83 % (BSX) (P=.450). The corresponding numbers at 12-months in the DES and BSX groups were 74 % and 80 % (P= .750). At 24 months the respective numbers were 56 % and 71 % (P=.830). There were no statistically significant differences in primary or assisted primary patency at 1, 6, or 12 months.
Conclusions:
There were no demonstrable differences in patency rates or clinical outcomes such as ABI or major amputations between DES and BSX. Although underpowered, the results suggest non-inferiority of the DES compared to prosthetic bypass surgery.
Trial registration:
The trial was pre-registered at ClinicalTrials.org (NCT01450722).
Purpose:
To report a randomized trial comparing the Legflow paclitaxel-eluting balloon (PEB) + Supera stenting to Supera stenting alone in patients with intermediate to long superficial femoral artery (SFA) lesions.
Methods:
The multicenter RAPID trial ( controlled-trials.com ; identifier ISRCTN47846578) randomized (1:1) 160 patients (mean age 67 years; 102 men) with Rutherford category 2-6 ischemia to treatment with Legflow PEB + Supera stent or Supera stent alone in intermediate to long SFA lesions (mean lesion length 15.8±7.4 vs 15.8±7.6 cm, respectively). The efficacy outcome was primary patency, defined as freedom from restenosis on duplex ultrasound or angiography.
Results:
Baseline characteristics including the percentage of occlusions were similar between groups. In the intention-to-treat analysis, the estimated primary patency at 1 year was 68.3% (95% CI 56.7% to 79.9%) in the PEB + Supera group vs 62.0% (95% CI 49.1% to 74.9%) in the Supera group (p=0.900). Per-protocol analysis showed a 12-month primary patency estimate of 74.7% (95% CI 63.1% to 86.3%) in the PEB + Supera group vs 62.0% (95% CI 49.1% to 74.9%) in the control group (p=0.273). Secondary patency estimates at 12 months (per-protocol analysis) were 89.0% (95% CI 80.6% to 97.4%) vs 98.0% (95% CI 94.1% to 100%; p=0.484); the estimates for freedom from clinically driven target lesion revascularization (CD-TLR) were 83.0% (95% CI 72.8% to 93.2%) and 77.8% (95% CI 66.6% to 89.0%; p=0.277), respectively.
Conclusion:
The short-term results from the multicenter RAPID randomized controlled trial indicate that the Legflow PEB is safe and feasible for the treatment of intermediate to long SFA lesions. In this trial, at least 70% of the patients suffered an occlusion. The PEB group had higher rates of primary patency and freedom from CD-TLR, although there were no statistically significant differences vs controls.
Purpose
The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally
advanced nasopharyngeal carcinoma is controversial. The individual patient data from theMeta-Analysis
of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments.
Methods
All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal
carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments
were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RTAC),
IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed
by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixedand
random-effects frequentist network meta-analysis models were applied.
Results
The three treatmentswith the highest probability of benefit on overall survival (OS) were CRT-AC, followed
by CRT and IC-CRT,with respective hazard ratios (HRs [95% CIs]) comparedwith RT alone of 0.65 (0.56 to
0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS,
progression-free survival (PFS), locoregional control, and distant control (DC)were, respectively, 0.85 (0.68
to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and
the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional
control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55
(0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity.
Conclusion
The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all
end points. The addition of IC to CRT achieved the highest effect on DC.
Purpose:
To report a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons (PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each other in the infrapopliteal arteries.
Methods:
Sixteen RCTs comprising 1805 patients with 1-year median follow-up were analyzed. Bayesian random effects binomial models were employed (WinBUGS). Relative treatment effects were expressed as odds ratios (ORs) with 95% credible intervals (CrI), and the cumulative rank probabilities were calculated to provide hierarchies of competing treatments. Quality of evidence (QoE) was assessed with the GRADE (grading of recommendations assessment, development, and evaluation) system. Sensitivity, heterogeneity, and consistency analyses were performed.
Results:
There was high QoE that infrapopliteal DES significantly reduced restenosis compared with BMS (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95% CrI 0.11 to 0.45). Likewise, DES significantly reduced target lesion revascularization (TLR) compared with BA (OR 0.41, 95% CrI 0.22 to 0.75) and BMS (OR 0.26, 95% CrI 0.15 to 0.45). Paclitaxel-coated balloons also reduced TLR compared with BA (OR 0.55, 95% CrI 0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18 to 0.67), but QoE was low to moderate. BA had lower TLR than BMS (OR 0.63, 95% CrI 0.40 to 0.99) with high QoE. DES was the only treatment that significantly reduced limb amputations compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB (OR 0.51, 95% CrI 0.26 to 0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with moderate to high QoE. DES also significantly improved wound healing compared with BA (OR 2.02, 95% CrI 1.01 to 4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with high QoE. Results were stable on sensitivity and meta-regression analyses without any significant publication bias or inconsistency.
Conclusion:
Infrapopliteal DES were associated with significantly lower rates of restenosis, TLR, and amputations and improved wound healing compared to BA and BMS. DES also significantly reduced amputations compared with PCB.
Objectives:
The aim of this study was to investigate the efficacy and safety of a new paclitaxel-coated balloon catheter in the treatment of stenotic or occluded femoropopliteal arteries.
Background:
The incidence of restenosis can be reduced by the use of drug-coated balloons. However, dose, coating composition, and technology are decisive for efficacy.
Methods:
Two hundred Chinese patients with peripheral arterial occlusive disease were prospectively randomized to treatment with new paclitaxel-coated or standard uncoated balloon catheters. The primary endpoint was angiographic late lumen loss at 6 months, measured by a blinded core laboratory. Secondary angiographic endpoints (6 months) and specific clinical endpoints (1 year) were binary restenosis, ankle-brachial index, Rutherford stage, clinically driven target lesion revascularization, and amputation.
Results:
Patients' mean age was 66 years, 74% were men, 31% were smokers, and 55% had diabetes. Patients were in Rutherford stages 2 through 5, with a mean lesion length of 150 mm; 25% had in-stent restenosis, 55% had occlusion or partial occlusion, and 20% underwent provisional stenting. Late lumen loss at 6 months was available for 89%, and clinical follow-up was available for >95% per group. Mean late lumen loss was 0.05 ± 0.73 mm with coated balloons and 1.15 ± 0.89 mm with uncoated balloons (p < 0.001). Correspondingly, the rates of restenosis were 22.5% and 70.8% (p < 0.001). After 1 year, the rates of target lesion revascularization were 7.2% and 39.6% (p < 0.001), and Rutherford class and ankle-brachial index improved more markedly in the coated group (p < 0.046 and p = 0.023, respectively). One major amputation was recorded in the control group. No coating-related adverse events were observed for doses of up to 43 mg paclitaxel per patient.
Conclusions:
In this medium-sized trial with long superficial femoral artery lesions, the use of paclitaxel-coated balloon catheters markedly improved angiographic and clinical outcomes of interventions despite advanced disease in the majority of patients.
Objectives:
The aim of BIOLUX P-II (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) trial was to compare the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon (percutaneous transluminal angioplasty [PTA]) in de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia.
Background:
DEB have shown promising results in femoropopliteal lesions, but data for infrapopliteal lesions are scarce.
Methods:
In this prospective, multicenter, randomized first-in-man study, 72 patients were randomized 1:1 to either a Passeo-18 Lux DEB (Biotronik AG, Buelach, Switzerland) (n = 36) or Passeo-18 PTA (n = 36). Follow-up assessments were scheduled at 1, 6, and 12 months, with angiographic assessment at 6 months. Adverse events were adjudicated by an independent clinical events committee, and angiographic parameters were assessed by an independent core laboratory.
Results:
The primary safety endpoint (a composite of all-cause mortality, target extremity major amputation, target lesion thrombosis, and target vessel revascularization at 30 days) was 0% in the DEB group versus 8.3% in the PTA group (p = 0.239). The primary performance endpoint (patency loss at 6 months) was 17.1% in the DEB group versus 26.1% in the PTA group (p = 0.298), and major amputations of the target extremity occurred in 3.3% versus 5.6% of the patients at 12 months, respectively.
Conclusions:
The Passeo-18 Lux DEB has been proven to be safe and effective in infrapopliteal lesions with comparable outcomes to PTA.
Background:
-Drug-coated balloon angioplasty (DCBA) was shown to be superior to standard balloon angioplasty (POBA) with regard to restenosis prevention for de-novo superficial femoral artery (SFA) disease. For in-stent restenosis (ISR), the benefit of DCBA over POBA remains uncertain.
Methods and results:
-One-hundred-nineteen patients with SFA ISR and chronic limb ischemia were recruited over 34 months at 5 German clinical sites and prospectively randomized to either DCBA (n = 62) or POBA (n = 57). Mean lesion length was 82.2 ± 68.4 mm. Thirty four (28.6%) lesions were totally occluded, 30 (25.2%) were moderately or heavily calcified. Clinical and duplex ultrasound follow-up was conducted at 6 and 12 months. The primary endpoint of recurrent ISR assessed by ultrasound at 6 months was 15.4% (8/52) in the DCBA and 44.7% (21/47) in the POBA group (P = 0.002). Freedom from target lesion revascularization (TLR) was 96.4 % vs. 81.0% (P = 0.0117) at 6 months and 90.8% vs. 52.6% (P < 0.0001) at 12 months, respectively. At 12 months, clinical improvement by ≥ 1 Rutherford category without the need of TLR was observed in 35/45 DCBA patients (77.8%) and 23/44 POBA patients (52.3%, P = 0.015). No major amputation was needed. Two patients in the DCBA and 3 patients in the POBA group died. No death was procedure-related.
Conclusions:
-DCBA for SFA ISR is associated with less recurrent restenosis and a better clinical outcome than POBA, without an apparent difference in safety. Clinical Trial Registration Information-www.clinicaltrials.gov. Identifier: NCT01305070.
To compare primary placement of a self-expanding nitinol stent to percutaneous transluminal angioplasty (PTA) with bailout stenting in infrapopliteal arteries of patients with severe intermittent claudication or critical limb ischemia (CLI).
In the EXPAND trial (ClinicalTrials.gov; identifier NCT00906022), 92 patients (mean age 72.9±9.5 years; 62 men) undergoing treatment for infrapopliteal stenosis in 11 European centers were randomized 1:1 to either self-expanding nitinol stenting with the Astron Pulsar/Pulsar-18 nitinol stent or PTA with bailout stenting. The primary endpoint was sustainable clinical improvement after 12 months, defined as a ≥1-category increase for Rutherford category 3 patients or a ≥2-category increase for CLI patients (Rutherford categories 4/5) compared with baseline. Furthermore, target lesion revascularization (TLR), mortality, and amputation were assessed after 12 months.
Sustained clinical improvement at 1 year was observed in 74.3% of the patients treated with primary stenting and in 68.6% of the patients treated with PTA and bailout stenting (p>0.05). Kaplan-Meier estimates of freedom from TLR (76.6% and 77.6%), mortality (7.4% vs 2.1%), and amputation [8.9% (major 6.7%) vs 13.2% (major 8.7%)] at 1 year were not significantly different.
Primary self-expanding nitinol stenting did not show statistically different clinical outcomes compared to angioplasty with bailout stenting for infrapopliteal lesions.
© The Author(s) 2015.
Background:
The treatment of peripheral artery disease with percutaneous transluminal angioplasty is limited by the occurrence of vessel recoil and restenosis. Drug-coated angioplasty balloons deliver antiproliferative agents directly to the artery, potentially improving vessel patency by reducing restenosis.
Methods:
In this single-blind, randomized trial conducted at 54 sites, we assigned, in a 2:1 ratio, 476 patients with symptomatic intermittent claudication or ischemic pain while at rest and angiographically significant atherosclerotic lesions to angioplasty with a paclitaxel-coated balloon or to standard angioplasty. The primary efficacy end point was primary patency of the target lesion at 12 months (defined as freedom from binary restenosis or from the need for target-lesion revascularization). The primary safety end point was a composite of freedom from perioperative death from any cause and freedom at 12 months from limb-related death (i.e., death from a medical complication related to a limb), amputation, and reintervention.
Results:
The two groups were well matched at baseline; 42.9% of the patients had diabetes, and 34.7% were current smokers. At 12 months, the rate of primary patency among patients who had undergone angioplasty with the drug-coated balloon was superior to that among patients who had undergone conventional angioplasty (65.2% vs. 52.6%, P=0.02). The proportion of patients free from primary safety events was 83.9% with the drug-coated balloon and 79.0% with standard angioplasty (P=0.005 for noninferiority). There were no significant between-group differences in functional outcomes or in the rates of death, amputation, thrombosis, or reintervention.
Conclusions:
Among patients with symptomatic femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon resulted in a rate of primary patency at 12 months that was higher than the rate with angioplasty with a standard balloon. The drug-coated balloon was noninferior to the standard balloon with respect to safety. (Funded by Lutonix-Bard; LEVANT 2 ClinicalTrials.gov number, NCT01412541.).