Early asymptomatic graft failure in coronary artery bypass grafting: a study based on computed tomography angiography analysis.

BACKGROUND: Asymptomatic graft failure after coronary bypass grafting surgery (CABG) may have negative impact on the patients' short- and long-term outcomes. Cardiac computed tomography angiography (CTA) has been proved to be another choice to detect graft failure besides coronary artery angiography in several studies. We aimed to identify the rate and predictors of asymptomatic graft failure detected by CTA before discharge. METHODS AND RESULTS: A total of 955 grafts of 346 consecutive asymptomatic patients who received CTA examination after CABGs were included in this retrospective study from July 2017 to Dec 2019. We divided 955 grafts into the patent group and occluded group by CTA results. Logistic regression model at graft-level were established to determine predictors of the early asymptomatic graft occlusion. The overall asymptomatic graft failure rate was 4.71% (45/955), and there was no difference between the arterial and venous conduits in different target territories (P > 0.05). The logistic regression at graft-level analysis showed that female (OR 3.181, CI 1.58-6.40, P = 0.001), composite grafting (OR 6.762, CI 2.26-20.28, P = 0.001), pulse index value (OR 1.180, CI 1.08-1.29, P < 0.001) and new postoperative atrial fibrillation (POAF) (OR2.348, CI 1.15-4.78, P = 0.018) were independent risk factors that affect graft failure, while early postoperative dual-antiplatelet treatment with aspirin and clopidogrel was a protective factor (OR 0.403, CI 0.19-0.84, P = 0.015). CONCLUSIONS: Early asymptomatic graft failure is associated with both patient and surgical factors including female gender, high PI value, composite graft strategy and the new POAF. However, the early dual- antiplatelet therapy with aspirin and clopidogrel may be useful for preventing graft failure.

Predictors of vein graft disease progression between one week and one year after surgical coronary revascularization: Impact of secondary prevention medications.

OBJECTIVE: This study aimed to detect the predictors of vein graft disease (VGD) progression between 1 week and 1 year after surgery and to evaluate the impact of secondary prevention medications. METHODS: A total of 218 consecutive patients underwent surgical coronary revascularization were evaluated by coronary computed tomography angiography both at 1-week and 1-year follow-up. Logistic regression analyses were performed to investigate the predictors of VGD progression. A risk score (0-4) was set up to evaluate implementation result of secondary prevention measures according to 1-year follow-up result. Association between VGD progression and the risk score was assessed. RESULTS: VGD progression occurred in 11.3% of saphenous vein grafts (SVG) and 22.1% of patients. At the patient level, poor vein graft (odds ratio [OR] = 4.25), noncontrolled hyperlipidemia (OR = 3.01), and diabetes mellitus (DM) (OR = 2.96) were predictors, while diameter of SVG (mm, OR = 0.35) was protective factor. At the graft level, DM (OR = 3.52), noncontrolled hyperlipidemia (OR = 2.33), and peripheral artery disease (PAD) (OR = 2.20) were predictors, while number of SVGs (OR = 0.63), diameter of SVG (mm, OR = 0.39), and mean graft flow >25 ml/min (OR = 0.35) were protective factors. VGD progression was significantly associated with the risk score at both the patient (OR = 1.52) and the graft level (OR = 1.38). CONCLUSIONS: Poor vein graft, noncontrolled hyperlipidemia and DM were predictors of VGD progression between 1 week and 1 year after surgery at the patient level, while larger SVG diameter was a protective factor. DM, PAD and noncontrolled hyperlipidemia were predictors at the graft level, while a number of SVGs, larger SVG diameter, and mean graft flow >25 ml/min were protective factors. Implementation failure of secondary prevention medications was associated with VGD progression from as early as 1 year after surgery.

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

External Support for Saphenous Vein Grafts in Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

Importance: Intimal hyperplasia and subsequent saphenous vein graft failure may have significant adverse clinical effects in patients undergoing coronary artery bypass surgery. External support of saphenous vein grafts has the potential to prevent vein graft dilation and hence slow the rate of intimal hyperplasia and increase long-term vein patency. Objective: To determine efficacy, as measured by intimal hyperplasia, and safety of an external saphenous vein graft support device in patients undergoing a coronary bypass graft procedure. Design, Setting, and Participants: This within-patient randomized, open-label, multicenter study was conducted at 17 Cardiothoracic Surgical Trials Network centers in North America. Between January 2018 and February 2019, 224 patients with multivessel coronary artery disease undergoing isolated bypass surgery were enrolled. For each patient, 1 of 2 vein grafts was randomized to receive external support or no support. Interventions: External vein graft support or no support. Main Outcomes and Measures: The primary efficacy end point was intimal hyperplasia area assessed by intravascular ultrasound at 12 months postrandomization for each study graft. Secondary confirmatory end points were lumen diameter uniformity assessed by angiography and graft failure (≥50% stenosis) by quantitative coronary angiography. Major cardiac and cerebrovascular events were collected through month 12. Results: Among 224 patients (mean [SD] age, 65.8 [8.3] years; 178 [79.5%] male), 203 (90.6%) were eligible for intravascular ultrasound, of which 85 (41.9%) had at least 1 study graft occluded or severely diseased at 12 months (55 supported, 56 unsupported). After imputation of data missing because of graft occlusion or severe disease, the estimated mean (SE) intimal hyperplasia area was 5.11 (0.16) mm2 in supported grafts and 5.79 (0.20) mm2 in unsupported grafts (P = .07). In a sensitivity analysis of 113 patients with both grafts imaged, the mean intimal hyperplasia area was 4.58 (0.18) mm2 and 5.12 (0.23) mm2 in supported and unsupported grafts, respectively (P = .04). By 12 months, 5 patients (2.2%) died and 16 patients (7.1%) experienced a major cardiac or cerebrovascular event. Conclusions and Relevance: The 12-month difference in intimal hyperplasia area between supported and unsupported grafts did not achieve statistical significance. Cumulative mortality and major cardiac or cerebrovascular events rates were similar to those in other randomized coronary artery bypass trials. Further investigation to assess the effect of external graft support devices on long-term graft patency and clinical outcomes is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03209609.

Ticagrelor versus aspirin 2 years after coronary bypass: Observational analysis from the TARGET trial.

BACKGROUND: Compared to conventional aspirin therapy, ticagrelor did not improve vein graft patency 1 year after coronary bypass surgery (CABG) in the ticagrelor antiplatelet therapy to reduce graft events and thrombosis (TARGET) trial. However, it is unknown whether ticagrelor may impact graft patency long-term following surgery. METHODS: In the TARGET multicenter trial, 250 CABG patients were randomized to aspirin 81 mg or ticagrelor 90 mg twice daily. In this observational analysis, 2 years after surgery, vein graft occlusion and clinical events were compared among subjects who agreed to a second year of double-blind study drug administration (N = 156). RESULTS: Two-year graft assessment was performed for 142 patients (80 aspirin patients, 62 ticagrelor patients, 425 total grafts), with an overall 2-year graft occlusion rate of 10.6%. Vein graft occlusion at 2 years, the primary outcome of this study, did not significantly differ between the two groups (15.7% vs. 13.2%, aspirin vs. ticagrelor, p = .71). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (19.4% vs. 19.8%, aspirin vs. ticagrelor, p = 1.00), and the number of patients with vein graft disease did not significantly differ between the groups (30.0% vs. 29.0%, aspirin vs. ticagrelor, p = 1.00). Vein grafts developing new disease did not significantly differ between the two groups (1.5% vs. 3.8%, aspirin vs. ticagrelor, p = .41). Freedom from major adverse cardiovascular events at 2 years was similar between the groups (p = .75). CONCLUSION: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft disease 2 years after CABG.

Commentary: Prevention of saphenous vein graft disease remains elusive.

One-year outcomes of Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET), a randomized double-blinded clinical trial comparing post-coronary artery bypass surgery antiplatelet therapy with ticagrelor versus aspirin are published in this issue of the Journal. Although the authors did not detect statistically significant differences in their primary outcome (saphenous vein graft patency at 1 year) and major adverse cardiovascular events, their findings must be interpreted with caution given important limitations in the design and execution of the trial.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Ticagrelor versus aspirin and vein graft patency after coronary bypass: A randomized trial.

BACKGROUND: Antiplatelet therapy prevents saphenous vein graft (SVG) occlusion and improves outcomes after coronary artery bypass graft surgery (CABG). However, the optimal postoperative antiplatelet regimen remains unclear. The goal of the Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) trial was to assess whether early postoperative ticagrelor reduces SVG occlusion compared to conventional aspirin therapy. METHODS: In this multi-center double-blind randomized trial, 250 patients who had CABG with SVG were randomized to receive either aspirin 81 mg twice daily or ticagrelor 90 mg twice daily. The primary outcome was SVG occlusion at 1 year. RESULTS: Altogether, 123 patients were randomized to aspirin and 127 received ticagrelor. One-year graft assessment was performed in 202 patients (80.8%), examining 588 grafts, yielding an overall graft occlusion rate of 10.9%. The primary outcome, SVG occlusion at 1 year, did not significantly differ between the two groups (17.4% vs. 13.2%, aspirin vs. ticagrelor, p = .30). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (21.5% vs. 22.3%, aspirin vs. ticagrelor, p = .90), and the number of patients with vein graft disease did not significantly differ between the groups (29.4% vs. 28.0%, aspirin vs. ticagrelor, p = .88). Freedom from major adverse cardiovascular events at 1 year was similar between the groups (p = .60). CONCLUSIONS: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft occlusion 1 year after CABG. Further study will assess the impact of ticagrelor on 2-year graft patency for this cohort.

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.

Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model.

AIM: According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents (DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. METHODS: Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy [DAPT] group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. RESULTS: OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. CONCLUSIONS: Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.

Poly (ɛ-Caprolactone-co-l,l-Lactide) Vascular External Sheath Carrying Prednisone for Improving Patency Rate of the Vein Graft.

Coronary artery bypass graft (CABG) surgery is an impactful treatment for coronary heart disease. Intimal hyperplasia is the central reason for the restenosis of vein grafts (VGs) after CABG. The introduction of external vascular sheaths around VGs can effectively inhibit intimal hyperplasia and ensure the patency of VGs. In this study, the well-known biodegradable copolymer poly (ɛ-caprolactone-co-l,l-lactide) (PLCL) was electrospun into high porosity external sheaths. The prednisone loaded in the PLCL sheath was slowly released during the degradation process of PLCL. Under the combined effects of sheath and prednisone, intimal hyperplasia was inhibited. For the cell experiments, all sheaths show low cytotoxicity to L929 cells at different concentrations at different time intervals. The ultrasonography and histological results showed prominent dilation and intimal hyperplasia of VG without sheath after 2 months of surgery. But there was no dilation in PLCL and PLCLPrednisone groups. Of note, the prednisone-loaded sheath group exhibited efficacy in inhibiting intimal hyperplasia and ensured graft patency. Impact statement To inhibit intimal hyperplasia after coronary artery bypass graft, the use of external vascular sheaths can prevent vein graft (VG) dilatation, then reduce turbulent blood flow shear stress to vessel wall, and lower the stimulation of shear stress to smooth muscle cells (SMCs), so as to prevent the proliferation and migration of vascular SMC. We provide a biodegradable sheath electrospun by poly (ɛ-caprolactone-co-l,l-lactide) (PLCL) loading prednisone and utilize it around VG in animal models. Vascular ultrasound examinations show strong evidence of vascular patency. The histological alterations of VGs in PLCLPrednisone group gave a narrower intima layer owing to the inhibition effect of prednisone.

Drug-coated balloon angioplasty for failing haemodialysis access: meta-analysis of randomized clinical trials.

BACKGROUND: Arteriovenous fistulas, a major treatment for end-stage kidney disease, frequently require endovascular reinterventions to maintain haemodialysis function. Drug-coated angioplasty balloons (DCBs) were developed with the intention of reducing reintervention rates. The aim of this study was to perform a systematic review and meta-analysis of DCBs in the treatment of failing haemodialysis access. METHODS: Electronic databases were searched systematically to identify all relevant RCTs and any follow-up studies from RCTs. Pooled estimates of dichotomous outcomes were calculated using the odds ratio (OR) and 95 per cent confidence interval. Effect data are presented as summary hazard ratio and 95 per cent confidence interval. RESULTS: Some 19 studies from 18 RCTs and comprising 1898 patients were included in the meta-analysis. Compared with plain balloon angioplasty (PBA), DCB use was associated with higher target-lesion primary patency (HR 0.60, 95 per cent c.i. 0.45 to 0.79), access-circuit primary patency (HR 0.67, 0.56 to 0.80), and less target-lesion revascularization (TLR) within 6 months (OR 0.33, 0.23 to 0.47). No difference was observed between DCB and PBA in 12-month TLR (OR 0.62, 0.28 to 1.37). Mortality after DCB use was similar to that associated with PBA use at 6 months (OR 1.20, 0.65 to 2.21) and 12 months (OR 0.99, 0.66 to 1.49), and was higher at 24 months (23.1 versus 16.6 per cent), although the difference was not statistically significant (OR 1.53, 0.92 to 2.53). CONCLUSION: Drug-coated balloon angioplasty of haemodialysis fistulas is associated with higher patency rates and lower rates of reintervention in the short to mid term. Although mortality rates appeared to be higher with drug-coated angioplasty at 24 months, this did not reach statistical significance.

Mechanisms, Prevention and Treatment of Saphenous Vein Graft Disease.

Saphenous vein grafts are imperfect yet indispensable conduits commonly used for coronary artery bypass grafting. Their degeneration ultimately leading to occlusion results from the pathological response of the vein to altered blood rheology and several types of vascular injury. Surgical techniques minimizing vessel damage, and prolonged antiplatelet and lipid-lowering treatment are established methods of mitigating the degeneration process hence preventing graft occlusions. Percutaneous interventions in degenerated vein grafts carry high risk of embolization, periprocedural myocardial infarction and restenosis. Thus, native vessel should be the preferred treatment target in case of graft failure whenever technically feasible.

Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients.

BACKGROUND: Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable complications of this procedure. We retrospectively evaluated whether adjuvant systemic heparinization just before arterial manipulation could reduce early failure of primary AVF. METHODS: Three hundred and fifty-six patients with end-stage renal failure who underwent primary AVF surgery from April 2009 to September 2020 were enrolled in this study. The patients were divided into two groups based on whether they received adjuvant heparinization or not. Patient backgrounds, frequency of early AVF failure, and bleeding events were compared between the two groups. Multivariate Cox regression analysis identified risk factors for early AVF failure. RESULTS: Early failure of AVF was observed in only 2 of 157 patients (1.2%) in the adjuvant group, and the incident was significantly lower than observed in the non-adjuvant group, i.e., 17 of 199 patients (8.5%) (p = 0.002). Bleeding events were not significantly different between the two groups. Seven of 157 patients (4.5%) in the adjuvant group and 7 of 199 patients (3.5%) in the non-adjuvant group experienced bleeding events (p = 0.785). Female sex, use of steroids, hypoalbuminemia, venous stenosis in pre-surgical evaluation, arterial spasm in the perioperative period, new-onset venous stenosis after AVF anastomosis, technical failure of surgery, no early cannulation after surgery, and non-adjuvant heparinization were related to early AVF failure in the multivariate regression analysis. CONCLUSION: Adjuvant systemic heparinization therapy just before arterial manipulation reduced early failure of primary AVF without increasing bleeding events.

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.

Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation.

AIM: Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency. DATA SYNTHESIS: One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM. CONCLUSION: We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

Dual Antiplatelet Therapy Duration After Venous Sinus Stenting for Idiopathic Intracranial Hypertension and Stent Survival-Is Longer Necessarily Better? A Meta-Regression.

BACKGROUND: Venous stenting (VS) for venous sinus stenosis in the setting of idiopathic intracranial hypertension has been increasing in acceptance by neurointerventionalists. Stent-adjacent stenosis (SAS) and in-stent stenosis leading to symptom recurrence and the need for retreatment are known delayed complications. However, the effect of the dual antiplatelet therapy (DAPT) duration on these complications has remained poorly characterized. METHODS: An extensive literature search was performed to identify reports of VS for patients with idiopathic intracranial hypertension from 2000 to 2020. The primary outcome was the occurrence of SAS. The secondary outcomes included the occurrence of composite stenosis (in-stent stenosis and SAS) and stent survival, defined as the need for retreatment or other surgical management. Generalized linear mixed models were used to explore the effects of DAPT duration (3 vs ≥6 months) on the primary and secondary outcomes. RESULTS: A total of 325 patients met the inclusion criteria and were included in our analysis. SAS occurred in 9% (95% confidence interval, 6%-15%) of the patients, and stent survival was 90% (95% confidence interval, 84%-93%) in the cohort. With every 1-mm Hg increase in the venous pressure gradient, an 8% decrease was found in the odds of stent survival (P = 0.043). The meta-regression revealed no association between the DAPT duration and the primary outcome or the odds of composite stenosis and stent survival. CONCLUSIONS: We found no differences between 3 and ≥6 months of DAPT in terms of the risk of stent stenosis or stent survival. However, patients with a higher venous pressure gradient before VS had a greater risk of stent failure.

Dual Antiplatelet Therapy De-escalation Strategies.

Dual antiplatelet therapy (DAPT), the combination of aspirin (ASA), and a P2Y12 inhibitor, protects against stent thrombosis and new atherothrombotic events after a stent implantation or an acute coronary syndrome, but exposes patients to an increased risk of bleeding. In most current practices, the P2Y12 inhibitor is stopped at 6 to 12 months and ASA is continued indefinitely. The advent of safer stents, with less risk of stent thrombosis, has challenged this standard of care, however. A number of alternative strategies involving earlier de-escalation of the antiplatelet therapy have therefore been proposed. In these approaches, standard DAPT is switched to a less potent antithrombotic combination at an earlier time-point than recommended by guidelines. Three different de-escalation variations have been tested to date. The first one maintains DAPT but switches from the potent P2Y12 inhibitors ticagrelor or prasugrel to either a lower dose or to clopidogrel, while maintaining ASA. The 2 other approaches involve changing DAPT to a single antiplatelet at some earlier time-point after the percutaneous coronary intervention procedure, by stopping either the P2Y12 inhibitor or ASA. These strategies have all demonstrated some benefit in clinical trials so far, but especially the contribution of ASA in secondary prevention is clearly evolving as its role in increasing bleeding complications while not providing increased ischemic benefit is becoming more and more clear. In contemporary practice, the type and duration of DAPT should now be based on an individualized decision, and the de-escalation strategies, if used wisely, can be added to the existing options.

Role and Timing of Aspirin Therapy Following PCI in Patients With Atrial Fibrillation.

In patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI), both anticoagulation and dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) are indicated. However, this "triple" antithrombotic therapy is associated with high rates of bleeding. Finding the right balance of reducing ischemic risk and protecting coronary stents from restenosis while not increasing bleeding risk is difficult. In the past 5 years, 6 randomized clinical trials have shown the benefit of dropping aspirin from the triple therapy regimen to create "dual" therapy (oral anticoagulants and P2Y12 inhibitors alone) with reductions in bleeding without a significant increase in ischemic events. Because of small trends toward higher risk of stent thrombosis, especially in higher risk patients with acute coronary syndromes, current recommendations call for dual therapy as the "default" regimen, but that risk stratification be used to help inform the decision on potentially using a brief period of triple therapy in selected high ischemic risk patients. For long-term therapy (after one year post-PCI), recent studies have found oral anticoagulation alone without any antiplatelet therapy has a favorable benefit risk ratio. Thus, while dropping aspirin at varying times post-PCI has become an attractive strategy in many patient groups, careful patient selection and individualized assessment of the risk:benefit balance is warranted.