Paclitaxel-coated Devices Research Articles

Long-term clinical outcome and mortality risks after paclitaxel-coated balloon angioplasty in patients with peripheral artery disease: An observational clinical study.

Background and aimsDrug‐eluting devices (DEDs) are usually used as a standard therapy for revascularization in femoropopliteal artery disease. Randomized controlled trails have found that DEDs with paclitaxel result in superior patency rates and decreased target lesion revascularization. A meta‐analysis by Katsanos et al indicated an increased long‐term mortality in patients treated with paclitaxel‐coated devices. The aim of this observational clinical study was to assess the long‐term clinical outcomes and mortality risk after paclitaxel‐coated balloon angioplasty in patients with symptomatic peripheral artery disease.MethodsWe retrospectively evaluated 287 patients with peripheral interventions, including 173 drug‐coated balloon (DCB) angioplasties and 114 plain old balloon angioplasties (POBA), performed at our center between 2015 and 2018.ResultsThere were no significant differences in mortality rates between patients who received DCB angioplasty and those who received POBA. In the first year, the hazard ratio (HR) for DCB angioplasty was 0.59 (95% confidence interval [CI] 0.31 to 1.12, P = .104). After 2 years, this HR was 0.64 (95% CI 0.36‐1.17, P = .145), while the 3‐year and 4‐year HR increased to 0.71 and 1.30 (3‐year: 95% CI 0.37‐1.33, P = ,283; 4‐year: 95% CI 0.55‐3.08, P = .546). No paclitaxel dose‐response relationship with mortality rate was identified when adjusted for key predictors of mortality.ConclusionsAnalyses of patient level data identified no significant mortality differences between DCB angioplasty and POBA after 4 years of follow‐up. Furthermore, there was no dose‐response relationship between paclitaxel and mortality. These findings demonstrate that paclitaxel DCB is safe. Further long‐term multicenter studies are needed to determine the risk of late mortality.

Rationale and Design of the SAFE-PAD Study.

Recent evidence from randomized controlled trials has raised concerns about the long-term safety of paclitaxel-coated peripheral devices used for femoropopliteal artery revascularization. In response to a call for more real-world data on the safety of these devices, the SAFE-PAD study (Safety Assessment of Femoropopliteal Endovascular treatment with Paclitaxel-coated Devices) was designed with input from the Food and Drug Administration to provide a long-term, comprehensive evaluation of the mortality risk associated with paclitaxel-coated devices among Medicare beneficiaries. SAFE-PAD is an observational cohort study of fee-for-service Medicare beneficiaries that underwent femoropopliteal artery revascularization with either a drug-coated device or nondrug-coated device from 2015 through 2018. All patients age 66 years or older who underwent revascularization will be identified using a combination of International Classification of Diseases, Tenth Revision procedural codes, Current Procedural Terminology codes, and Healthcare Common Procedure Coding System C-codes. The safety end point of all-cause death will be updated semiannually and continued until the median duration of follow-up surpasses 5 years. Sub-group analyses will be conducted by device type, patient characteristics, and procedural setting. Registration: The SAFE-PAD study has been registered on URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496544. The SAFE-PAD study will evaluate the long-term safety of drug-coated devices compared with nondrug-coated devices for femoropopliteal artery revascularization among a broad, real-world population of patients with peripheral artery disease.

Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease

BackgroundThe results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.MethodsWe conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated–device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.ResultsNo patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated–device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated–device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated–device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).ConclusionsIn this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.)

Paclitaxel-coated devices in the treatment of femoropopliteal stenosis among patients ≥65 years old: An ACC PVI Registry Analysis

The connection between paclitaxel-coated devices (PCD) use during peripheral vascular interventions (PVI) and mortality is debated. We aimed to analyze patterns of PCD use and the safety and effectiveness of PCD use in the superficial femoral and/or popliteal arteries. Patients undergoing PVI of femoropopliteal lesions with and without PCD between January 1, 2015 and June 30, 2017 were compared using the American College of Cardiology's National Cardiovascular Data Registry PVI Registry. Outcomes were derived from Centers for Medicare & Medicaid claims data. The primary outcome was all-cause mortality at 6-, 12-, and 24-months following PVI. Inverse probability weighting and frailty models were used to assess the differences between groups. The analysis was IRB-approved. In the overall cohort consisting of 6,302 femoropopliteal PVIs, PCD-PVI patients were more likely to be treated for claudication (63.5% vs 51.3%, P< .001), less likely to have a chronic total occlusion (24.6% vs 34.7%, P < .001), and more likely to be treated in certain geographic and practice settings. In the analytic cohort consisting of 1,666 femoropopliteal PVIs with linked claims outcomes (888 PCD-PVI, 53.3%), unadjusted rates of all outcomes were lower in PCD-PVI patients. After adjustment, there were no significant differences in mortality following PCD-PVI versus non-PCD PVI at 1 year (adjusted RR 0.78, 95% CI 0.60-1.01, P= .055) or 2 years (aRR 0.98, 95% CI 0.77-1.24, P= .844). There were significant differences between the patients in whom and settings in which PCD-PVI was versus was not used. PCD-PVI was not associated with an increased risk of 2-year mortality in real-world use.

Outcomes of treatment with paclitaxel-coated devices for peripheral arterial disease

ObjectiveThe treatment of femoropopliteal peripheral artery disease (PAD) using paclitaxel-coated devices (PCDs) has been shown to improve patency in several randomized trials. However, a recent meta-analysis of trial data suggested an increased risk of mortality with PCD usage. Although subsequent studies have found no association with mortality, the subject has remained controversial. Thus, the aim of the present study was to further investigate the outcomes and causes of mortality for patients treated with PCDs. MethodsPatients who had undergone endovascular interventions for PAD from 2013 to 2016 at a single institution were reviewed. The patients were stratified by the use of PCDs, which included drug-coated balloons and drug-eluting stents. The cumulative dose of paclitaxel was calculated for the patients who had received multiple interventions. The causes of mortality were identified and compared between the two groups. ResultsOf the 366 included patients, 138 (38%) had received a PCD and 228 (62%) had received a non–drug-coated (NDC) device. Patients treated with PCDs were less likely to have undergone open surgery compared with patients treated with NDC devices. No differences were found in the indications or 30-day outcomes between the two groups. After a mean follow-up of 3.1 ± 1.8 years, no differences were found in the primary patency, reintervention rate, mean number of reinterventions, major amputation (5% vs 4%; P = .465), or mortality (16% vs 20%; P = .363) between the PCD and NDC groups. Also, no overall difference was found in the cause of mortality with and without PCD use or in the Kaplan-Meier survival curves. Furthermore, PCD use was not associated with an increased risk of mortality in Cox regression analysis. The cumulative dose of paclitaxel in patients treated with PCDs ranged from 383 to 49,259 μg (median, 7561 μg). A comparison of the patients treated with a cumulative dose of paclitaxel in the upper 50th percentile compared with the lower 50th percentile showed no significant differences in mortality (13% vs 19%; P = .333). ConclusionsPCD use was shown to be safe and not associated with an increased risk of long-term mortality in the present study. Continued monitoring of PCD use is warranted to ensure the safety of this technology.

Paclitaxel-Coated Peripheral Arterial Devices are Associated with Reduced Mortality in Younger Patients

Paclitaxel-coated devices have been shown to decrease restenosis when used in the femoropopliteal artery. Recent reports have suggested a possible risk of increased late mortality in patients treated with paclitaxel. It has been suggested that younger patients and those with limited comorbidities may be at higher risk. Our objective was to analyze long-term mortality based on patient age comparing treatment with paclitaxel to uncoated devices. We performed a retrospective review of 1,170 consecutive patients who underwent femoropopliteal percutaneous intervention by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. Patients were grouped by age at the time of procedure: <60years old (n=244, 20.9%), 60-80years old (n=635, 54.3%), and >80years old (n=291, 24.9%). Within each group, patients were further divided by use of paclitaxel. The primary outcome measure was survival assessed by Kaplan-Meier analysis. Differences between the groups were analyzed with analysis of variance. Multivariable analysis was performed using Cox proportional hazard models. Of the 1,170 patients who underwent femoropopliteal percutaneous intervention, 654 (55.9%) received a paclitaxel-coated device during treatment and 516 (44.1%) did not. Mean age of the overall patient cohort was 70.4±12.6years and 663 (56.7%) were male. When comparing the groups by age we found an increase in age but a decrease in the proportion of patients who smoke. The use of paclitaxel-coated devices was similar across the groups (<60years old, 56.2%; 60-80years old, 57.0%; >80years old, 52.6%; P=0.45). Demographics and comorbidities were similar between the patients treated with and without paclitaxel within each age group except more males in the <60-year-old group treated without paclitaxel and more patients with chronic limb threatening ischemia in the >80-year-old group treated with paclitaxel. In patients <60 and 60-80years old paclitaxel use was associated with increased survival at 4years: <60 (80.7% vs. 64.4%; P=0.04); 60-80 (63.2% vs. 55.1%; P=0.04). Survival was similar in the >80-year-old group (46.6% vs. 32.8%; P=0.65). Our data suggest that the use of paclitaxel-coated arterial devices is not associated with increased mortality. On the contrary, our data show that younger patients treated with paclitaxel show improved survival compared with those treated without paclitaxel. Paclitaxel-coated devices may be used with continued caution especially in patients at high risk for restenosis.

Assessment of Mortality and Factors Affecting Outcome of Use of Paclitaxel-Coated Stents and Bare Metal Stents in Femoropopliteal PAD.

The use of drug-coated devices in intravascular therapy is aimed at preventing neointimal hyperplasia caused by excessive proliferation of vascular smooth muscle and thereby restenosis. Although its use seemed initially promising, a recent publication has shown an increased risk of mortality with paclitaxel-coated devices, and there is an urgent need to reaffirm assessments of drug-eluting stents (DES). Objective: The aim of the study was to compare mortality and effectiveness of paclitaxel-coated stents and bare-metal stents (BMS) in the treatment of peripheral arterial disease (PAD) with long-term follow-up. Materials and methods: In a single center randomized study, 256 patients with PAD were treated intravascularly with stent implantation. Patients were randomized into two groups: the first (n = 126) were treated with DES, and the second (n = 130) were treated with BMS. The study included evaluation after the procedure, after about 6 months and 36 months. Co-morbidities, with risks for atherosclerosis, were analyzed in all patients. Patients were evaluated for clinical outcome, restenosis frequency, and safety (complications and total mortality). Results: Clinical benefit at the end of the investigation was statistically significantly better in the DES group compared with the BMS group: 85.7% versus 66.2% (p = 0.0003), respectively. Restenosis occurred significantly less frequently in patients with DES: 16.0% versus BMS: 35.0%, p = 0.012. There was no significant effect of comorbidities on the frequency of restenoses. There were no differences in all-cause mortality over the three years with paclitaxel and no-paclitaxel stents cohorts (8.7% versus 7.1%; long-rank p = 0.575). No association was found with mortality and treatment with DES or BMS. Conclusions: The use of paclitaxel-coated stents gave good clinical benefit and caused a significantly lower frequency of restenosis compared to bare-metal stents. The use of paclitaxel-coated stents did not increase mortality.

Increased mortality with paclitaxel-eluting stents is driven by lesion length

BackgroundEndovascular stenting has become the first-line treatment of symptomatic peripheral artery disease of the femoropopliteal axis (FPA). Several randomized clinical trials have reported that paclitaxel-eluting stents (PESs) significantly reduce the rates of restenosis. However, a meta-analysis investigating paclitaxel-coated devices in the FPA showed a significant increase in all-cause mortality after the use of PES. The aim of this study was to compare the long-term, real-world outcomes of bare-metal stents (BMSs) and PESs for treating FPA occlusive disease. MethodsA retrospective review of the medical records of 296 patients who underwent FPA stenting between January 2011 and December 2017 was performed. Patients were grouped into BMS and PES groups. The primary end point was all-cause mortality. Secondary end points included limb salvage, primary patency, primary assisted patency, and secondary patency. A comparison between the two groups within TransAtlantic Inter-Society Consensus (TASC) II subgroups was also performed. ResultsOf the study cohort, 101 patients (34%) received PES, whereas 195 patients (66%) underwent BMS placement. Median follow-up time was 23 months (interquartile range, 7-40 months). The 2-year all-cause mortality estimates were 12% for the PES group compared with 11.4% for the BMS group (P = .26). There were no differences in the 2-year limb salvage (90.7% vs 92%; P = .4), primary patency (78.8% vs 81.1%; P = .62), primary assisted patency (100% vs 96.5%; P = .4), and secondary patency (100% vs 98.6%; P = .26) between the PES and the BMS groups, respectively (all P > .05). These findings persisted when patients were stratified by TASC II lesions. Among patients with TASC C and D lesions, the use of PES was associated with significantly higher 2-year all-cause mortality (23.9% vs 5.1%; P = .05). After adjustment for age and other potential confounders, PES use was associated with significant increase in all-cause mortality (adjusted hazard ratio, 2.3; 95% confidence interval, 1.31-27 P = .02) in TASC C and D patients. ConclusionsConsistent with the meta-analysis of several randomized clinical trials, the use of PES in a real-world setting was associated with a twofold increase in the risk of death. However, these findings were seen only among patients with TASC C and D lesions, who required multiple longer stents and potentially larger paclitaxel dose. There was no advantage in terms of patency in PES vs BMS in this population with extensive disease. Further studies of larger populations are required.

Evaluation of Mortality Following Paclitaxel Drug-Coated Balloon Angioplasty of Femoropopliteal Lesions in the Real World

ObjectivesThis study sought to evaluate the long-term mortality after paclitaxel drug-coated balloon (DCB) angioplasty and plain old balloon angioplasty (POBA) of femoropopliteal lesions in real-world practice. BackgroundA recent meta-analysis of randomized controlled trials suggested an increased long-term mortality risk following femoropopliteal angioplasty using paclitaxel-coated devices. MethodsA retrospective mortality analysis of patients with at least 3-year follow-up who underwent balloon based endovascular therapy of femoropopliteal lesions was performed. ResultsOverall, 7,357 patients with femoropopliteal lesions were treated within the study period receiving either DCB angioplasty or POBA. Of those, 1,579 fulfilled the study criteria. A total of 514 patients were treated with POBA without crossover to a paclitaxel-coated device during follow-up and 1,065 patients were treated with DCB angioplasty. Mortality incidence at mean follow-up of 52.0 ± 20.5 months (median 51 months) was 27.8% after POBA and 16.9% after DCB angioplasty (p < 0.001). Equally, for a cohort excluding patients over 80 years of age, the mortality rate after POBA treatment was significantly higher (23.6% vs. 12.3%; p < 0.001). For the entire cohort, independent predictors for mortality were age (p < 0.001), type of treatment (p = 0.009), hyperlipidemia (p = 0.010), diabetes mellitus (p = 0.010), renal insufficiency (p = 0.007), stroke (p = 0.017), and Rutherford-Becker class 4 (p < 0.001). DCB length was not correlated to mortality rate. After propensity score matching, independent mortality predictors were POBA treatment (p = 0.035), age (p < 0.001), stroke (p = 0.025), and renal insufficiency (p = 0.007). ConclusionsIn this real-world retrospective analysis, the long-term mortality rate was lower after DCB angioplasty than after POBA of femoropopliteal lesions. Known comorbidities, risk factors, and disease severity were identified as mortality predictors but not paclitaxel.

Outcomes of Treatment With Paclitaxel-Coated Devices for Peripheral Arterial Disease

Treatment of femoropopliteal peripheral artery disease using paclitaxel-coated devices (PCD) has been shown to improve patency in several randomized trials. However, a recent meta-analysis of trial data suggested an increased risk of mortality with the use of this technology. Although subsequent studies have found no association with mortality, real-world data are lacking. Thus, the aim of this study is to investigate real-world outcomes and causes of mortality of patients treated with PCD. Patients who underwent endovascular interventions for peripheral artery disease from 2013 to 2016 at a single institution were reviewed. Patients were stratified based on the use of PCD. The cumulative dose of paclitaxel over a 3-year period was calculated among patients who received multiple interventions. Causes of mortality were identified and compared between the two groups. There were 138 (37.7%) patients who received an endovascular intervention with a PCD and 228 (62.3%) who received an endovascular intervention without paclitaxel. Patients treated with PCD were less likely to have prior open surgery compared to patients treated without paclitaxel. There were no differences in indication, TransAtlantic Inter-Society Consensus classification, or 30-day outcomes between the two groups. After 3-year follow-up, there was no difference in primary patency, reintervention rate, mean number of reinterventions, amputation (5.1% vs 3.5%; P = .465), or mortality (15.9% vs 19.7%; P = .363) between the PCD and non-PCD groups (Table). There was also no overall difference in the causes of mortality with and without PCD use or in the Kaplan-Meier survival curves (Figure). Furthermore, the use of PCD was not associated with an increased risk of mortality in Cox regression analysis. The cumulative dose of paclitaxel in patients treated with PCD ranged from 383 to 49,259 μg with a median dose of 7561 μg. Comparison of patients treated with cumulative doses of paclitaxel in the upper 50th percentile compared to the lower 50th percentile showed no significant difference in mortality (13.0% vs 19.1%; P = .333). PCD use is safe and not associated with an increased risk of long-term mortality in this study. However, PCD use was not associated with improved LER outcomes. Continued monitoring of PCD is warranted to ensure safety and efficacy of this new technology in a real-world setting.TableDemographics, comorbidities, procedural characteristics, and outcomesNon-PCD paclitaxelPCDP valueDemographics and comorbidities No. of patients228138 Age (years)69.7 ± 11.469.7 ± 11.6.866 Male sex148 (64.9)89 (64.5).935 Race.693White171 (77.0)102 (77.7)African American33 (14.9)16 (12.2)Other18 (8.1)13 (9.9) Body mass index27.5 ± 5.929.2 ± 6.4.015 Diabetes120 (52.6)73 (52.9).960 Hypertension205 (89.9)133 (96.4).024 Coronary artery disease133 (58.3)75 (54.4).456 Chronic renal insufficiency31 (13.7)26 (18.8).192 Smoking.250Nonsmoker37 (16.4)30 (21.7)Former116 (51.3)73 (52.9)Current73 (32.3)35 (25.4) Prior endovascular revascularization53 (23.4)31 (22.5).846 Prior open revascularization30 (13.2)8 (5.8).025 Preoperative ABI0.7 ± 0.30.8 ± 0.3.290 Indication.195Asymptomatic5 (2.2)1 (0.7)Claudication131 (57.5)91 (65.9)Chronic limb-threatening ischemia92 (40.4)46 (33.3)Medications Antiplatelet192 (84.2)109 (79.0).205 Statin161 (70.6)99 (71.7).818Procedure characteristics TASC classification.227TASC A24 (26.1)22 (23.4)TASC B29 (31.5)22 (23.4)TASC C12 (13.0)9 (9.6)TASC D27 (29.4)41 (43.6)30-Day outcomes Return to operating room16 (7.3)9 (6.8).872 Any complication34 (14.9)17 (12.3).487 Mortality4 (1.75)0 (0.0).1183-Year outcomes Primary patency73 (52.4)45 (42.9).150 Ipsilateral reintervention67 (29.4)53 (38.4).075 Ipsilateral major amputation8 (3.5)7 (5.1).465 All-cause mortality45 (19.7)22 (15.9).363Deaths.807 No. of patients4522 Cause of deathCardiovascular12 (26.7)9 (40.9)Cancer5 (11.1)1 (4.5)Respiratory2 (4.4)2 (9.1)Neurologic1 (2.2)0 (0.0)Gastrointestinal2 (4.4)1 (4.6)Renal0 (0.0)0 (0.0)Infectious8 (17.8)3 (13.6)Other/unspecified15 (33.3)6 (27.3)ABI, Ankle-brachial index; PCS, paclitaxel-coated device; TASC II, Inter-Society Consensus of the Management of Peripheral Artery Disease.Values are mean ± standard deviation or number (%), unless otherwise indicated. Open table in a new tab

Characterizing Treatment Preference “Phenotypes” Among Patients With Symptomatic Peripheral Artery Disease to Support Identification of Concordant Treatment and Communication Strategies

Patient input into treatment decisions is potentially useful for choices between options, especially for tradeoffs between risk and benefit in the setting of clinical equipoise, such as use of paclitaxel-coated devices. Clinicians lack efficient methods of eliciting patient preferences or applying this information to treatment selection, however. We quantified preferences and values of patients with peripheral artery disease and characterized group-wise preferences using latent class methods.

How Safe Are Paclitaxel-Coated Devices for Treatment of Peripheral Artery Disease?

Paclitaxel-eluting balloons and stents have substantial benefits in reducing repeat procedures in patients undergoing catheter-based interventions for

Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Meta-Analysis.

Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.

A Single-Center Experience of Paclitaxel in the Treatment of Femoropopliteal Disease-No Evidence for an Association With Mortality.

Paclitaxel-coated devices have been increasingly used in endovascular treatment of femoropopliteal disease as they limit recurrence of lesions and improve patient outcomes. However, a recent meta-analysis reported that these devices increase mortality risk at 2 years post-intervention but did not account for confounding variables. Therefore, our goal was to evaluate mortality after paclitaxel treatment of femoropopliteal disease using patient-level data. We performed a retrospective review of all patients who received endovascular treatment for femoropopliteal lesions at our center between December 2009 and July 2017. There were 388 patients in the paclitaxel group and 314 control patients. Survival analysis with hazard ratios showed no difference between mortality in the paclitaxel and control groups. Age, renal insufficiency, and chronic limb-threatening ischemia were significant predictors of mortality. We also used logistic regression to evaluate mortality at 1, 2, and 5 years post-intervention and found no difference between the paclitaxel and control groups at any time point, while age, renal insufficiency, and chronic limb-threatening ischemia at the time of intervention were all associated with the risk of death. Finally, we tallied the causes of death in our cohort and found no difference in the distribution of causes between groups. Our single-center, retrospective study provides no evidence of increased risk of death with paclitaxel treatment in femoropopliteal disease. Contrastingly, age, renal insufficiency, and chronic limb-threatening ischemia were the most important factors contributing to mortality and therefore should be included as potential confounders in future studies assessing mortality in femoropopliteal disease.

Survival After Coronary Revascularization With Paclitaxel-Coated Balloons

BackgroundDrug-coated balloons (DCBs) are accepted treatment strategies for coronary in-stent restenosis and are under clinical investigation for lesions without prior stent implantation. A recently published meta-analysis suggested an increased risk of death associated with the use of paclitaxel-coated devices in the superficial femoral artery. The reasons are incompletely understood as potential underlying pathomechanisms remain elusive, and no relationship to the administered dose has been documented. ObjectivesThe purpose of this analysis was to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomized controlled trials (RCTs). MethodsPubMed, Web of science, and the Cochrane library database were searched, and a meta-analysis from RCT was performed comparing DCB with non-DCB devices (such as conventional balloon angioplasty, bare-metal stents, or drug-eluting stents) for the treatment of coronary in-stent restenosis or de novo lesions. The primary outcome was all-cause death. The number of patients lost to follow-up was observed at different time points. Risk estimates are reported as risk ratios (RRs) with 95% confidence intervals (CIs). ResultsA total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analyzed. At follow-up of 6 to 12 months, no significant difference in all-cause mortality was found, however, with numerically lower rates after DCB treatment (RR: 0.74; 95% CI: 0.51 to 1.08; p = 0.116). Risk of death at 2 years (n = 1,477, 8 RCTs) was similar between the 2 groups (RR: 0.84; 95% CI: 0.51 to 1.37; p = 0.478). After 3 years of follow-up (n = 1,775, 9 RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR: 0.73; 95% CI: 0.53 to 1.00; p = 0.047) with a number needed to treat of 36 to prevent 1 death. A similar reduction was seen in cardiac mortality (RR: 0.53; 95% CI: 0.33 to 0.85; p = 0.009). ConclusionsIn this meta-analysis, the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality, as has been suggested for peripheral arteries. On the contrary, use of coronary paclitaxel-coated balloons was associated with a trend toward lower mortality when compared with control treatments.

Mortality After Paclitaxel-Coated Device Use in Patients With Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose: To report the risk of all-cause mortality after treatment with paclitaxel-coated devices vs uncoated controls in patients with chronic limb-threatening ischemia (CLTI). Materials and Methods: A search of the PubMed, Embase, Cochrane, CINAHL, DARE, and PROSPERO databases was made on 5 November 2019 to identify randomized controlled trials (RCT) using intention-to-treat analysis to compare a paclitaxel-coated device to an uncoated device in PAD patients having clinical follow-up of at least 6 months. Half of the study population had to have CLTI or extractable data on the CLTI subgroup if <50%. The search identified 11 trials having 1450 patients randomized to a paclitaxel-coated device (n=866) or an uncoated control (n=584). There were 1367 (94.3%) patients with CLTI (range 10–429). The single endpoint was all-cause mortality, which was analyzed by pooling the mortality data in a DerSimonian and Laird random effects model. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). Results: The mean follow-up was 25.6 months (range 6–60); 10 of 11 studies reported a minimum 12-month follow-up. There were 161 (18.6%) deaths among 866 subjects in the paclitaxel device group and 116 deaths among 584 (19.9%) subjects in the non-coated control group (RR 0.93, 95% CI 0.78 to 1.12, p=0.45). Conclusion: There was no observed difference in short- to midterm mortality among a pooled patient population of predominately CLTI patients treated with paclitaxel-coated balloons or stents compared with uncoated controls.

The IN.PACT DEEP Clinical Drug-Coated Balloon Trial: 5-Year Outcomes

ObjectivesThe goal of this study was to evaluate the 5-year follow-up data of the IN.PACT DEEP (Randomized IN.PACT Amphirion Drug-Coated Balloon [DCB] vs. Standard Percutaneous Transluminal Angioplasty [PTA] for the Treatment of Below-the-Knee Critical Limb Ischemia [CLI]) trial. BackgroundInitial studies from randomized controlled trials have shown comparable short-term outcomes of DCB angioplasty versus PTA in patients with CLI with infrapopliteal disease. However, the long-term safety and effectiveness of DCB angioplasty remain unknown in this patient population. MethodsIN.PACT DEEP was an independently adjudicated prospective, multicenter, randomized controlled trial that enrolled 358 subjects with CLI. Subjects were randomized 2:1 to DCB angioplasty or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, amputation, and all-cause death. Additional assessments were conducted to identify risk factors for death and major amputation, including paclitaxel dose tercile. ResultsFreedom from clinically driven target lesion revascularization through 5 years was 70.9% and 76.0% (log-rank p = 0.406), and the incidence of the safety composite endpoint was 59.8% and 57.5% (log-rank p = 0.309) in the DCB angioplasty and PTA groups, respectively. The rate of major amputation was 15.4% for DCB angioplasty compared with 10.6% for PTA (log-rank p = 0.108). Given the recent concern regarding a late mortality signal in patients treated with paclitaxel-coated devices, additional analyses from this study showed no increase in all-cause mortality with DCB angioplasty (39.4%) compared with PTA (44.9%) (log-rank p = 0.727). Predictors of mortality included age, Rutherford category >4, and previous revascularization but not paclitaxel by dose tercile. ConclusionsTibial artery revascularization in patients with CLI using DCB angioplasty resulted in comparable long-term safety and effectiveness as PTA. Paclitaxel exposure was not related to increased risk for amputation or all-cause mortality at 5-year follow-up. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733)

Paclitaxel-coated Peripheral Arterial Devices Are Associated with Reduced Mortality In Younger Patients

Paclitaxel-coated Peripheral Arterial Devices Are Associated with Reduced Mortality In Younger Patients

Paclitaxel-coated peripheral artery devices are not associated with increased mortality

ObjectiveLong-term safety concerns have been raised that the use of paclitaxel-coated balloons and stents is linked to excess mortality. Our objective was to compare outcomes in patients treated with paclitaxel vs uncoated devices and to analyze long-term mortality. MethodsWe conducted a retrospective single-institution review of 1170 consecutive patients who underwent femoropopliteal percutaneous revascularization by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. The primary outcome measure was all-cause mortality. Groups were divided into patients who received paclitaxel (n = 652) and those who did not (n = 518). Categorical variables were assessed using χ2 analysis and continuous variables with the Wilcoxon signed rank test. A multivariable analysis was performed using multivariable logistic regression models. Mortality was compared using Kaplan-Meier survival analysis. ResultsDemographics, risk factors, and Rutherford class were similar between the groups, except that the paclitaxel group was more likely to have diabetes (60.9% vs 55.0%; P = .04), was less likely to be on dialysis (10.7% vs 14.9%; P = .04), and had lower average creatinine concentration (1.6 ± 1.8 mg/dL vs 2.0 ± 2.3 mg/dL; P = .003). There were no differences in all-cause mortality through 2 years between paclitaxel and no-paclitaxel cohorts (25.5% vs 30.3%; log-rank, P = .098). At 3 years and 3.5 years, mortality was significantly lower in the paclitaxel group: year 3, 32.1% vs 39.4% (log-rank, P = .041); year 3.5, 35.2% vs 43.9% (log-rank, P = .027). Survival rates were not significantly different in examining subgroups by diabetes, chronic kidney disease, presence of chronic limb-threatening ischemia, or paclitaxel-coated balloon manufacturer. Multivariable analysis demonstrated that age, dialysis, chronic limb-threatening ischemia, chronic kidney disease, and congestive heart failure were independent risk factors for mortality, whereas paclitaxel use was associated with lower mortality. ConclusionsThe use of paclitaxel-coated balloons and stents does not increase mortality compared with uncoated devices out to 3.5 years. Paclitaxel-coated devices can be used with continued caution, especially in patients at increased risk of restenosis. Further long-term studies are needed to determine the risk of late mortality.

Safety Issues Associated with Paclitaxel-Eluting Balloons and Progress of Sirolimus-Eluting Balloons

Drug eluting balloons (DEBs) are semi-compliant angioplasty balloons covered with an antiproliferative drug which is rapidly released locally into the vessel wall during balloon contact. Their advantages include a broader area of drug contact, more homogenous drug-tissue transfer for stent-based local drug delivery, no implant leaving as well as shortened dual antiplatelet therapy. DEBs application was first recommended by the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) guidelines for the treatment of in-stent restenosis (ISR) after prior bare-metal stent (BMS) (Class IIA, Level B) in 2010. Since then, rapid progress has been made in the use of DEBs for treatment of in-stent restenosis, bifurcation, small vessel diseases, and other de novo occlusive coronary artery diseases even the symptomatic peripheral arterial disease. However, a meta-analysis of 28 randomized controlled trials (RCTs) with 4663 patients investigating paclitaxel-coated devices (DEBs & drug-eluting stent) in the femoral and/or popliteal arteries showed a highly significant association between risk of death and paclitaxel exposure in a dose-time-dependent manner. Safety issues associated with clinical application of paclitaxel DEBs in femoropopliteal artery was widely discussed. This study reviewed the issues, different molecular mechanisms of paclitaxel and sirolimus in antiproliferative effects, and progress of sirolimus-eluting balloons.