Influence of lipoproteins and antiplatelet agents on vein graft patency 1 year after coronary artery bypass grafting.

OBJECTIVE: It remains unclear whether aggressive low-density lipoprotein cholesterol (LDL-C) management (<1.8 mmol/L) can slow the process of vein graft stenosis. This study aimed to explore the impact of baseline LDL-C levels on vein graft patency in patients on ticagrelor with or without aspirin 1 year after coronary artery bypass grafting (CABG). METHODS: This was a post hoc analysis of the DACAB (Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery) trial (NCT02201771), a randomized controlled trial (ticagrelor + aspirin or ticagrelor vs aspirin) of patients undergoing CABG in China. The study subjects were stratified as LDL-low (baseline LDL-C <1.8 mmol/L, 148 patients with 430 vein grafts) versus LDL-high (baseline LDL-C ≥1.8 mmol/L, 352 patients with 1030 vein grafts). The primary outcome was the 1-year vein graft patency (Fitzgibbon grade A) assessed by coronary computed tomographic angiography or coronary angiography. RESULTS: Baseline/1-year LDL-C were 1.4/1.6 and 2.6/2.4 mmol/L in the LDL-low and LDL-high subgroups, respectively. Regardless of antiplatelet regimen, no significant inter-subgroup difference was observed for 1-year graft patency (LDL-low: 83.8% [359/430 grafts]; LDL-high: 82.3% [848/1030 grafts]; adjusted OR for non-patency [ORadj], 0.96; 95% confidence interval [CI], 0.62-1.50, P = .857). For both subgroups, the 1-year graft patency rates were greater with ticagrelor + aspirin versus aspirin (LDL-low: ORadj, 0.41; 95% CI, 0.17-0.97; LDL-high: ORadj, 0.38; 95% CI, 0.20-0.71; inter P = .679). CONCLUSIONS: In general, baseline LDL-C is not associated with 1-year vein graft patency after CABG. Regardless of the baseline LDL-C levels, ticagrelor + aspirin was superior to aspirin alone in maintaining vein graft patency. The primary factor causing early vein graft disease might not be atherosclerosis but thrombosis.

Comparison of functional patency rates between paclitaxel-eluting versus plain balloon angioplasty in hemodialysis patients with central venous stenosis: An intra-individual comparison study.

Central venous stenosis (CVS) is usually a late-diagnosed clinical entity that is common in hemodialysis patients. It causes various problems ranging from hemodialysis difficulty to loss of the arterio-venous (A-V) fistula. In the present study, we aimed to determine the effect of drug eluting balloon while excluding the influence of other variable factors by evaluating the same individuals with plain and paclitaxel-eluting balloons. This research was a prospective study of 18 symptomatic hemodialysis patients (age 50.9 ± 14.0 years, range 32-72 years; 11 male, 7 female) with CVS who underwent treatment by plain balloon angioplasty (PBA) and paclitaxel-eluting balloon angioplasty (PEBA) in our hospital from January 2016 to June 2017. First, third and sixth month central vein patency rates were compared. The median patency rates of central veins were 109.0 (range: 10-324) days after PBA and 238.5 (range: 157-501) days after PEBA (p < 0.001). There was no statistically significant difference between PBA and PEBA angioplasty in one-month patency (p Ëƒ 0.05). By contrast, a statistically significant difference was found between 3- and 6-month patency rates (p = 0.031 and p Ë‚ 0.001, respectively). Kaplan-Meier analysis revealed that the primary cumulative patency rate of PEBA was significantly longer than that of PBA (p ˂ 0.001). In this prospective study, PEBA patency is superior to PBA patency in the treatment of CVS in dialysis patients.

Effect of Systemic Intraoperative Heparin Use on Upper Extremity Arteriovenous Fistula Patency in End-Stage Renal Disease Patients.

The formation of the arteriovenous fistula is an important method of vascular access for patients with end-stage renal disease (ESRD). This allows renal filtration resulting in improved life quality and expectancy for ESRD patients. The biggest drawback to arteriovenous fistula formation is thrombosis, which can occur at an early or delayed stage. One suggested method of reducing postoperative arteriovenous fistula thrombosis rates is the administration of intraoperative systemic heparin. Heparin use in this context is debated, and there is currently no consensus on its use. There are a number of small randomised control studies trialling use of heparin but no large systematic trials. In this report, we collate existing evidence in the form of a review article and attempt to extrapolate a consensus of the evidence.

Vasodilator agents improve hemodialysis vascular access patency: A population-based study from Korea.

ABSTRACT: Vascular access (VA) failure is an important problem for patients undergoing hemodialysis, and maintaining VA patency is challenging. In this study, we used a nationwide database to investigate the effects of nitrate, as a vasodilator, on VA failure in hemodialysis patients.We investigated the Korean insurance claims data of hemodialysis patients who underwent angioplasty for VA failure between January 2012 and December 2017. The patients were divided into 2 groups: those not receiving vasodilator therapy (controls) and those receiving any vasodilator administration (vasodilator treatment, VDT). The primary endpoint was VA primary patency, defined as the time between arteriovenous dialysis access creation and the first percutaneous transluminal angioplasty (PTA).During the study period, a total of 6350 patients were recruited, 409 (6.4%) patients assigned to the VDT group and 5941 (93.6%) controls. PTA was performed in 998 patients (15.7%), including 8 in the VDT group and 990 controls. The VA site PTA rate was significantly lower in the VDT group (2.0%) than in the control group (16.7%, P < .001). In the subgroup analysis, the patency rates associated with the different vasodilators were similar (P = .736). All vasodilators, except molsidomine, improved the patency rate by approximately 20%.In this large national database study, vasodilator administration was associated with higher VA primary patency, compared with controls, in hemodialysis patients. VDT may have a beneficial effect on maintaining VA patency in patients undergoing hemodialysis.

Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts.

BACKGROUND: People with end-stage renal disease (ESRD) often require either the formation of an arteriovenous fistula (AVF) or an interposition prosthetic arteriovenous graft (AVG) for haemodialysis. These access sites should ideally have a long life and a low rate of complications (e.g. thrombosis, infection, stenosis, aneurysm formation and distal limb ischaemia). Although some of the complications may be unavoidable, any adjuvant technique or medical treatment aimed at decreasing complications would be welcome. This is the fourth update of the review first published in 2003. OBJECTIVES: To assess the effects of adjuvant drug treatment in people with ESRD on haemodialysis via autologous AVFs or prosthetic interposition AVGs. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and ClinicalTrials.gov trials register to 6 August 2020. SELECTION CRITERIA: Randomised controlled trials of active drug versus placebo in people with ESRD undergoing haemodialysis via an AVF or prosthetic interposition AVG. DATA COLLECTION AND ANALYSIS: For this update, two review authors (IM, MFAK) independently selected trials for inclusion, extracted data, assessed risk of bias and assessed the certainty of the evidence according to GRADE. We resolved disagreements by discussion or consultation with another review author (ADS). The primary outcome was the long-term fistula or graft patency rate. Secondary outcomes included duration of hospital stay; complications such as infection, aneurysm formation, stenosis and distal limb ischaemia; and number of related surgical or radiological interventions. MAIN RESULTS: For this update, one additional study was suitable for inclusion, making a total of 13 trials with 2080 participants. Overall the certainty of the evidence was low or moderate due to short follow-up periods, heterogeneity between trials, small sample sizes, and risk of bias due to incomplete reporting. Medical adjuvant treatments used in the included trials were aspirin, ticlopidine, dipyridamole, dipyridamole plus aspirin, warfarin, fish oil, clopidogrel, sulphinpyrazone and glyceryl trinitrate (GTN) patch.  All included studies reported on graft patency by measuring graft thrombosis. There was insufficient evidence to determine if there was a difference in graft patency in studies comparing aspirin versus placebo (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.07 to 2.25; 3 studies, 175 participants; low-certainty evidence). The meta-analysis for graft patency comparing ticlopidine versus placebo favoured ticlopidine (OR 0.45, 95% CI 0.25 to 0.82; 3 studies, 339 participants; moderate-certainty evidence). There was insufficient evidence to determine if there was a difference in graft patency in studies comparing fish oil versus placebo (OR 0.24, 95% CI 0.03 to 1.95; 2 studies, 220 participants; low-certainty evidence); and studies comparing clopidogrel and placebo (OR 0.40, 95% CI 0.13 to 1.19; 2 studies, 959 participants; moderate-certainty evidence). Similarly, there was insufficient evidence to determine if there was a difference in graft patency comparing the effect of dipyridamole versus placebo (OR 0.46, 95% CI 0.11 to 1.94; 1 study, 42 participants, moderate-certainty evidence) and dipyridamole plus aspirin versus placebo (OR 0.64, CI 0.16 to 2.56; 1 study, 41 participants; moderate-certainty evidence); comparing low-intensity warfarin with placebo (OR 1.76, 95% CI 0.78 to 3.99; 1 study, 107 participants; low-certainty evidence); comparing sulphinpyrazone versus placebo (OR 0.43, 95% CI 0.03 to 5.98; 1 study, 16 participants; low-certainty evidence) and comparing GTN patch and placebo (OR 1.26, 95% CI 0.63 to 2.54; 1 study, 167 participants; moderate-certainty evidence). The single trial evaluating warfarin was terminated early because of major bleeding events in the warfarin group. Only two studies published data on the secondary outcome of related interventions (surgical or radiological); there was insufficient evidence to determine if there was a difference in related interventions between placebo and treatment groups. None of the included studies reported on the duration of hospital stay.  Most studies reported complications ranging from mortality to nausea. However, data on complications were limited and reporting varied between studies. AUTHORS' CONCLUSIONS: The meta-analyses of three studies for ticlopidine (an antiplatelet treatment), which all used the same dose of treatment but with a short follow-up of only one month, suggest ticlopidine may have a beneficial effect as an adjuvant treatment to increase the patency of AVFs and AVGs in the short term. There was insufficient evidence to determine if there was a difference in graft patency between placebo and other treatments such as aspirin, fish oil, clopidogrel, dipyridamole, dipyridamole plus aspirin, warfarin, sulphinpyrazone and GTN patch. The certainty of the evidence was low to moderate due to short follow-up periods, the small number of studies for each comparison, small sample sizes, heterogeneity between trials and risk of bias due to incomplete reporting. Therefore, it appears reasonable to suggest further prospective studies be undertaken to assess the use of these antiplatelet drugs in renal patients with an AVF or AVG.

[One-year results of conservative and endovascular treatment of deep venous thrombosis followed by severe acute venous insufficiency]. / Odnoletnie rezul'taty konservativnogo i endovaskulyarnogo lecheniya tromboza glubokikh ven s razvitiem tyazheloi ostroi venoznoi nedostatochnosti.

OBJECTIVE: To compare the results of conservative and endovascular treatment of deep vein thrombosis followed by acute severe venous insufficiency. MATERIAL AND METHODS: Two statistically valid groups of patients with deep vein thrombosis and acute severe venous insufficiency were compared. Warfarin was administered in the first group, endovascular methods - in the second group (n=30). At the first step, we performed catheter-guided thrombolysis, then transcutaneous mechanical thrombectomy and venous stent deployment. Anticoagulation was achieved with Apixaban. Hemorrhagic complications were monitored during the treatment. One-year results were assessed considering lumen patency restoration and severity of venous congestion with Villalty score. RESULTS: In the first group, each third patient had hemorrhagic complications that required cessation of anticoagulant therapy in 1.3% of patients. In the second group, hemorrhagic events occurred in 10% of patients and were managed by lowering Apixaban dosage. Complete restoration of lumen patency was detected in 23.3% in the first group and 93.3% in the second group. Partial restoration developed in 63.3% and 6.7%, occlusion in 13.3% and 0%, respectively. Only 23.3% of patients in the first group had no clinical evidence of venous congestion. Mild congestion was found in 20%, severe - in 56.7% of cases. In the second group, 6.7% of patients had minimal venous congestion.

Effects of dual antiplatelet therapy on graft patency after lower extremity bypass.

OBJECTIVE: Current guidelines recommend single-agent antiplatelet therapy for patients with symptomatic peripheral artery disease and consideration of dual antiplatelet therapy (DAPT) after surgical revascularization. The objective of this study was both to explore prescribing patterns of single antiplatelet therapy vs DAPT after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. METHODS: A retrospective analysis of prospectively collected nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) with captured long-term follow-up was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Linear regression investigated temporal trends in antiplatelet use. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. RESULTS: Of the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft or percutaneous coronary intervention, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis based on bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort (primary patency: HR, 0.81 [95% CI, 0.66-1.00; P = .05]; primary assisted patency: HR, 0.74 [95% CI, 0.58-0.94; P = .01]; and secondary patency: HR, 0.60 [95% CI, 0.44-0.82; P < .001]). No patency differences were observed on adjusted subgroup analysis for the other bypass conduits. CONCLUSIONS: A significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits. Further study is warranted to investigate optimal duration of DAPT therapy and its possible bleeding complications in prosthetic bypass patients.

Fast-track thrombolysis protocol for acute limb ischemia.

OBJECTIVE: Catheter-directed thrombolysis in the treatment of acute lower extremity arterial occlusions often requires several interventional sessions to generate successful outcomes. It is typically an expensive procedure, necessitating extended hospital length of stay (LOS) that may be associated with an increase in both local and systemic hemorrhagic complications. Five years ago, we created the fast-track thrombolysis protocol for arteries (FTTP-A) to deal with these concerns. The goal of our protocol is to re-establish patency during the first session of thrombolysis, thus decreasing costs and complications associated with prolonged periods of thrombolytic exposure. METHODS: A retrospective study of 42 patients who were treated for acute limb ischemia at our institution by FTTP-A from January 2014 to February 2019 was performed. FTTP-A includes periadventitial lidocaine injection at the arterial puncture site under ultrasound guidance, contrast arteriography of the entire targeted segment, pharmacomechanical rheolytic thrombectomy of the occluded arterial segment, tissue plasminogen activator infusion along the occluded segment, balloon maceration of the thrombus, and (if deemed necessary) placement of a stent in an area of significant (≥30%) stenosis that is refractory to balloon angioplasty and thrombolysis. After the stenosis or thrombus is cleared, patients are prescribed an oral anticoagulant agent. RESULTS: Primary FTTP-A (50 total interventions) was performed in 42 patients. The median age of patients was 67.2 ± 12.2 years (range, 41-98 years), and 54.8% were male; 59.5% of the procedures were performed on the left lower extremity. Initial arterial access was obtained through the common femoral artery in 39 of 42 cases (92.9%); in the remaining 3 cases, it was obtained in a left bypass access site, a right femoral-popliteal graft, and a right femoral-femoral graft. The mean operative time was 148.9 ± 62.9 minutes (range, 83-313 minutes), and the mean volume of tissue plasminogen activator infused was 9.7 ± 4.0 mg (range, 2-20 mg). The median cost including medications and interventional tools was $4673.19 per procedure. The mean postoperative LOS was 3.1 ± 4.5 days (range, 1-25 days). Median postoperative LOS was 1 day. Mean postoperative follow-up was 27 ± 19.2 months (range, 0-62 months). Single-session FTTP-A was successful in 81% (n = 34/42) of patients; the remaining 8 patients (19%) required a single additional session. Of the 42 patients, 34 (81%) required arterial stenting. Periprocedural complications consisted of one patient with hematuria, which resolved, and one patient with thrombocytopenia, which resolved. No patients experienced rethrombosis within 30 days of FTTP-A. During the 5-year study period, there was no significant local or systemic hemorrhage, limb loss, or mortality related to this protocol. CONCLUSIONS: FTTP-A appears to be a safe, efficacious, and cost-effective procedure in the resolution of acute lower extremity arterial occlusions.

Prediction Model for Freedom from TLR from a Multi-study Analysis of Long-Term Results with the Zilver PTX Drug-Eluting Peripheral Stent.

PURPOSE: Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions. METHODS: Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was generated for three example patient profiles via combinations of patient and lesion factors. TLR was defined as reintervention performed for ≥ 50% diameter stenosis after recurrent clinical symptoms. RESULTS: The model used records from 2227 patients. The median follow-up time was 23.9 months (range: 0.03-60.8). The Kaplan-Meier estimates for ffTLR were 90.5% through 1 year and 75.2% through 5 years. In a multivariate analysis, sex, age, Rutherford classification, lesion length, RVD, total occlusion, and prior interventions were significant factors. The example patient profiles have predicted 1-year ffTLRs of 97.4, 92.3, and 86.0% and 5-year predicted ffTLRs of 92.8, 79.5, and 64.8%. The prediction model is available as an interactive web-based tool ( https://cooksfa.z13.web.core.windows.net ). CONCLUSIONS: This is the first prediction model that uses an extensive dataset to determine the impact of patient and lesion factors on ffTLR through 5 years and provides an interactive web-based tool for expected patient outcomes with the Zilver PTX DES. CLINICAL TRIAL REGISTRATIONS: Zilver PTX RCT unique identifier: NCT00120406; Zilver PTX single-arm study unique identifier: NCT01094678; Zilver PTX China study unique identifier: NCT02171962; Zilver PTX US post-approval study unique identifier: NCT01901289; Zilver PTX Japan post-market surveillance study unique identifier: NCT02254837. LEVELS OF EVIDENCE: Zilver PTX RCT: Level 2, randomized controlled trial; Single-arm study: Level 4, large case series; China study: Level 4, case series; US post-approval study: Level 4, case series Japan PMS study: Level 4, large case series.

Effect of short-term low molecular weight heparin on patency following successful salvage of arteriovenous access with recurrent thrombosis.

AIM: This study aims to investigate the effect of low molecular weight heparin (LMWH) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. METHODS: Following successful thrombectomy, 66 patients with recurrent thrombosis were included in the study. The primary, assisted primary and secondary patency rates of patients who received LMWH (n = 24) were compared with those who did not receive anticoagulant (n = 42) using Kaplan-Meier analysis. Cox-regression analysis was performed to investigate potential predictors of patency rates. RESULTS: The mean dose of enoxaparin used was 40 ± 13.1 mg or 0.74 ± 0.2 mg/kg daily for a median duration of 14 (IQR 7,28) days. The mean trough anti-Xa concentrations measured after two doses of LMWH was 0.17 ± 0.13 IU/mL. Kaplan-Meier analyses for mean primary, assisted primary and secondary patency rates of LMWH vs no anticoagulation groups were 149 (95% CI: 91 - 207) vs 87 (95% CI: 42-132) days (P < .006), 230 (95% CI: 142-320) vs 107 (95% CI: 62-150) days (P = .01) and 438 (299-579) vs 294 (95% CI: 197-392) days (P = .08) respectively. LMWH remained a significant protective predictor of primary (HR: 0.49; 95% CI: 0.25-0.86; P = .02) and assisted primary patency rates (HR: 0.51; 95% CI: 0.27-0.98; P = .04) after adjusting for patient age, access age, type of AV access, presence of peripheral vascular disease and haemoglobin levels. CONCLUSION: LMWH may improve short and mid-term patency rates for AV accesses with recurrent thrombosis.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Heparin-bonded versus standard polytetrafluoroethylene arteriovenous grafts: A Bayesian perspective on a randomized controlled trial for comparative effectiveness.

BACKGROUND: Heparin-bonded polytetrafluoroethylene grafts were marketed to improve hemodialysis access outcomes but are twice the cost of standard polytetrafluoroethylene. We launched a randomized trial of heparin-bonded polytetrafluoroethylene versus standard polytetrafluoroethylene for hemodialysis access to compare patency. Since the trial began, additional studies were published with heterogeneous findings. We performed an interim analysis by Bayesian methods using prior probability from meta-analysis of existing literature. METHODS: NCT01601873 is a randomized, blinded trial of heparin-bonded polytetrafluoroethylene versus standard polytetrafluoroethylene for dialysis access at 5 sites. Planned sample size was 200 with 1-year primary patency as the primary endpoint. At interim analysis (50% of sample size at 1 year), we also performed a meta-analysis for 1-year primary patency with a random effects model to compute summary rate ratio and standard-error estimates. Meta-analysis estimates formed a prior probability for a Bayesian Cox regression model, and trial data were reanalyzed to develop posterior probability of heparin-bonded polytetrafluoroethylene effectiveness at our hypothesized effect size. Futility analysis was conducted using posterior probability estimates. RESULTS: One hundred and five patients were enrolled at the time of interim analysis. One-year primary patency was 34.9% in the heparin-bonded-polytetrafluoroethylene group vs 32.7% in the standard-polytetrafluoroethylene group (P = .884). Summary rate ratio from the meta-analysis (1,209 patients) was 0.87 favoring heparin-bonded polytetrafluoroethylene (P = .33). Posterior hazard ratio from Cox regression was 0.90 (credible interval 0.70-1.13) favoring heparin-bonded polytetrafluoroethylene, which was not significant. Bayesian posterior probability of the a priori hypothesized 20% better patency with heparin-bonded polytetrafluoroethylene was 24%. Sample size to detect superiority with the small observed effect size would require about 3,800 subjects. CONCLUSION: Current evidence does not demonstrate sufficiently large benefit of heparin-bonded polytetrafluoroethylene over standard polytetrafluoroethylene for dialysis access to justify higher cost. Given similar 1-year patency rates, a conclusive finding of superiority was judged to be infeasible, and the trial was stopped for futility.

Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula.

While the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have no effect on the outcomes of endovascular revascularization in tibial arterial occlusive disease.

The effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARBs) on angiogenesis, myocardial remodeling and intermittent claudication have been studied. Clinical studies have shown reduced re-intervention after cardiac stenting with the use of ACEI/ARBs. We hypothesized that the use of ACEI/ARBs decreases re-interventions after endovascular revascularization in tibial artery disease (TAD) patients. This is a retrospective study comparing the effects of ACEI/ARBs on the outcomes after endovascular revascularization for TAD. We divided all patients that underwent endovascular revascularization into Angiotensin converting enzyme inhibitor/Angiotensin receptor blockers (ACEI/ARBs) and No Angiotensin converting enzyme inhibitor/Angiotensin receptor blockers (NoACEI/ARBs) groups. A total of 360 patients underwent endovascular intervention for TAD. One hundred and ninety-six (54%) patients, 124 (57%) males, were on ACEI/ARBs after endovascular intervention for TAD, whereas 164(46%) patients, 87 (53%) males were not. The groups were well matched in the demographic variables except higher incidence of congestive heart failure, coronary artery disease and dialysis in the ACEI/ARBs group (p = .001, 0.02, 0.01 respectively). Reintervention rates were not associated with ACEI/ARBs use (p = .097). Even when corrected for statin use and antiplatelet therapy, no difference was seen in the reintervention rates in the two groups (p = .535, 0.547 respectively). Primary patency, assisted primary patency and secondary patency did not differ with the use of ACEI/ARBs (p = .244 0.096,0.060 respectively). No difference was seen in overall survival between the two groups (p = .690). ACEI/ARBs do not appear to affect the patency and reintervention rates for patients undergoing endovascular revascularization for TAD.

In vitro hemo- and cytocompatibility of bacterial nanocelluose small diameter vascular grafts: Impact of fabrication and surface characteristics.

OBJECTIVE: There is an increasing need for small diameter vascular grafts with superior host hemo- and cytocompatibilities, such as low activation of platelets and leukocytes. Therefore, we aimed to investigate whether the preparation of bacterial nanocellulose grafts with different inner surfaces has an impact on in vitro host cytocompatibility. METHODS: We have synthesized five different grafts in a bioreactor, namely open interface surface (OIS), inverted (INV), partially air dried (PAD), surface formed in air contact (SAC) and standard (STD) that were characterized by a different surface roughness. The grafts (length 55 mm, inner diameter 5 mm) were attached to heparinized polyvinyl chloride tubes, loaded with human blood and rotated at 37°C for 4 hours. Then, blood was analyzed for frequencies of cellular fractions, oxidative products, soluble complement and thrombin factors. The results were compared to clinically approved grafts made of polyethylene terephthalate and expanded polytetrafluoroethylene. Additionally, blood platelets were labelled with 111Indium-oxine to visualize the distribution of adherent platelets in the loop by scintigraphy. RESULTS: SAC nanocellulose grafts with the lowest surface roughness exhibited superior performance with <10% leukocyte and <50% thrombocyte loss in contrast to other grafts that exhibited >65% leukocyte and >90% thrombocyte loss. Of note, SAC nanocellulose grafts showed lowest radioactivity with scintigraphy analyses, indicating reduced platelet adhesion. Although the levels of reactive oxygen species and cell free DNA did not differ significantly, the levels of thrombin-antithrombin complexes were lowest in SAC grafts. However, all nanocellulose grafts exhibited enhanced complement activation. CONCLUSION: The systematic variation of the inner surfaces of BNC vascular grafts significantly improves biocompatibility. Especially, SAC grafts exhibited the lowest loss of platelets as well as leukocytes and additionally significantly diminished activation of the coagulation system. Further animal studies are needed to study in vivo biocompatibilities.

Effect of carvedilol on arteriovenous graft primary patency.

BACKGROUND: The major mechanisms of arteriovenous graft (AVG) failure due to intimal hyperplasia (IH) are smooth muscle cell proliferation and inflammation. Therefore, carvedilol may improve AVG primary patency because of its anti-proliferative and anti-inflammatory activities. METHODS: The data of end-stage renal disease patients receiving regular hemodialysis were collected from the National Health Insurance Research database. The end point was the first percutaneous transluminal angioplasty (PTA) for AVG failure or death during a follow-up period of two years or the end of 2013. The analysis was calculated with Cox proportional hazard model. RESULTS: There were 3028 patients treated with carvedilol and 13,704 patients not treated with carvedilol. According to a univariate analysis, the carvedilol group was younger, received more anti-hypertensive medications and platelet aggregation inhibitors, and had higher rates of diabetes mellitus and hyperlipidemia but had lower rates of hypotension and smoking. According to a multivariate analysis, after controlling for covariates, the use of carvedilol for more than 84 days reduced the probability of a first PTA for AVG failure by 9% compared with no use of carvedilol (p = 0.021), but the use of carvedilol for 1 to 84 days did not. CONCLUSION: The results of this study indicate that the use of carvedilol for more than 84 days improves the primary patency of AVGs, but the use of carvedilol for less than 84 days does not.

Natural history of acute pediatric iliofemoral artery thrombosis treated with anticoagulation.

OBJECTIVE: Acute iliofemoral artery thrombosis (IFAT) can occur in critically ill neonates and infants who require indwelling arterial cannulas for monitoring or as a consequence of cardiac catheterization. Guidelines suggest treatment with anticoagulation, but evidence supporting the optimal duration of therapy and the role of surveillance ultrasound is limited. The objectives of this study were to characterize the kinetics of thrombus resolution and to define an appropriate duration of anticoagulation and interval for surveillance ultrasound. METHODS: This was a single-center retrospective cohort study of pediatric patients with acute IFAT from 2011 to 2019. Medical records and vascular laboratory studies were reviewed. Patients with one or more surveillance ultrasound examinations were included. Thrombus resolution was defined as multiphasic flow throughout the index limb without evidence of echogenic intraluminal material by ultrasound. Time to resolution of thrombus was assessed using Kaplan-Meier analysis. RESULTS: Fifty-four limbs in 50 patients were identified with acute IFAT. The median age was 9.9 weeks (interquartile range, 3.1-21.7 weeks), with a median weight of 4.2 kg (interquartile range, 3.3-5.5 kg). The majority of limbs (65%) with acute IFAT presented with a diminished pedal Doppler signal, commonly after cardiac catheterization (55%). Forty-eight (89%) limbs had complete arterial occlusion on index ultrasound, and flow could not be detected below the ankle in 48%. The median number of ultrasound examinations per limb was three (range, two to seven), and 61% of limbs had a surveillance ultrasound within 7 days of diagnosis. At 14 and 30 days, 33% and 64% of patients, respectively, treated with anticoagulation had an estimated complete resolution of thrombus. Nine (17%) patients did not receive anticoagulation, and only two of these patients experienced IFAT resolution. At the time of diagnosis, one patient underwent open thrombectomy because of a contraindication to anticoagulation, and one patient was treated with thrombolysis. There were no instances of tissue loss or amputation CONCLUSIONS: Management of IFAT with anticoagulation resulted in successful short-term outcomes. Based on the observed rate of resolution, management should start with anticoagulation, followed by surveillance ultrasound at 2-week intervals. With treatment by anticoagulation, resolution can be expected to occur in one-third of patients every 2 weeks.

Combined effect of left stellate ganglion blockade and topical administration of papaverine on left internal thoracic artery blood flow in patients undergoing coronary revascularization.

Background: Left stellate ganglion blockade (LSGB) may have additive effect to topical administration of papaverine on prevention of vasospasm of left internal thoracic artery (LITA). Aims: This study aims to compare LITA blood flow with topical application of papaverine alone or in combination with LSGB. Setting: Tertiary care hospital. Design: Prospective randomized controlled study. Materials and Methods: A total of 100 patients operated for coronary revascularization were randomly and equally allocated into two groups. In control Group-C, papaverine was applied topically during the dissection of LITA. In Group-S, the additional LSGB was performed. Blood flow was measured from cut end of the LITA for 15 s. Primary objectives of the evaluation were to observe differences in the LITA blood flow. Observing incidence of radial-femoral arterial pressure difference after cardiopulmonary bypass (CPB) was secondary objective. Statistical Analysis: Student's unpaired t-test and Fisher's exact test to find out a significant difference between the groups. Results: LITA flow in Group-S was insignificantly more (49.28 ± 7.88 ml/min) than Group-C (47.12 ± 7.24 ml/min), (P = 0.15). Radio-femoral arterial pressure difference remained low for 40 min after termination of CPB in the Group-S compared to the Group-C (-0.99 ± 1.85 vs. -1.92 ± 2.26). Conclusion: Combining LSGB with papaverine does not increase the LITA blood flow compared to when the papaverine is used alone. However, ganglion blockade reduces radial-femoral arterial pressure difference after CPB. Blockade can be achieved successfully under the ultrasound guidance without any complications.

Endothelin-1, endothelin receptor antagonists, and vein graft occlusion in coronary artery bypass surgery: 20 years on and still no journey from bench to bedside.

The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was "Visiting Old and Learning New". This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients.

Atorvastatin Reduces In Vivo Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula.

BACKGROUND: Arteriovenous fistulas placed surgically for dialysis vascular access have a high primary failure rate resulting from excessive inward remodeling, medial fibrosis, and thrombosis. No clinically established pharmacologic or perisurgical therapies currently address this unmet need. Statins' induction of multiple anti-inflammatory and antithrombotic effects suggests that these drugs might reduce arteriovenous fistula failure. Yet, the in vivo physiologic and molecular effects of statins on fistula patency and maturation remain poorly understood. METHODS: We randomized 108 C57Bl/6J mice to receive daily atorvastatin 1.14 mg/kg or PBS (control) starting 7 days before end-to-side carotid artery-jugular vein fistula creation and for up to 42 days after fistula creation. We then assessed longitudinally the effects of statin therapy on primary murine fistula patency and maturation. We concomitantly analyzed the in vivo arteriovenous fistula thrombogenic and inflammatory macrophage response to statin therapy, using the fibrin-targeted, near-infrared fluorescence molecular imaging agent FTP11-CyAm7 and dextranated, macrophage-avid nanoparticles CLIO-VT680. RESULTS: In vivo molecular-structural imaging demonstrated that atorvastatin significantly reduced fibrin deposition at day 7 and macrophage accumulation at days 7 and 14, findings supported by histopathologic and gene-expression analyses. Structurally, atorvastatin promoted favorable venous limb outward remodeling, preserved arteriovenous fistula blood flow, and prolonged primary arteriovenous fistula patency through day 42 (P<0.05 versus control for all measures). CONCLUSIONS: These findings provide new in vivo evidence that statins improve experimental arteriovenous fistula patency and maturation, indicating that additional clinical evaluation of statin therapy in patients on dialysis undergoing arteriovenous fistula placement is warranted.