Magnetically powered microwheel thrombolysis of occlusive thrombi in zebrafish.

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ~25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis. Transparent zebrafish larvae have a highly conserved coagulation cascade that enables studies of hemostasis and thrombosis in the context of intact vasculature, clotting factors, and blood cells. Here, we show that tPA-functionalized µwheels can perform rapid and targeted recanalization in vivo. This effect requires both tPA and µwheels, as minimal to no recanalization is achieved with tPA alone, µwheels alone, or tPA-functionalized microparticles in the absence of a magnetic field. We evaluated tPA-functionalized µwheels in CRISPR-generated plasminogen (plg) heterozygous and homozygous mutants and confirmed that tPA-functionalized µwheels are dose-dependent on plasminogen for lysis. We have found that magnetically powered µwheels as a targeted tPA delivery system are dramatically more efficient at plasmin-mediated thrombolysis than systemic delivery in vivo. Further development of this system in fish and mammalian models could enable a less invasive strategy for alleviating ischemia that is safer than directed thrombectomy or systemic infusion of tPA.

Moving toward disease modification in polycythemia vera.

Polycythemia vera (PV) belongs to the BCR-ABL1-negative myeloproliferative neoplasms and is characterized by activating mutations in JAK2 and clinically presents with erythrocytosis, variable degrees of systemic and vasomotor symptoms, and an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia (AML). Treatment selection is based on a patient's age and a history of thrombosis in patients with low-risk PV treated with therapeutic phlebotomy and aspirin alone, whereas cytoreductive therapy with either hydroxyurea or interferon alfa (IFN-α) is added for high-risk disease. However, other disease features such as significant disease-related symptoms and splenomegaly, concurrent thrombocytosis and leukocytosis, or intolerance of phlebotomy can constitute an indication for cytoreductive therapy in patients with otherwise low-risk disease. Additionally, recent studies demonstrating the safety and efficacy (ie, reduction in phlebotomy requirements and molecular responses) of ropegylated IFN-α2b support its use for patients with low-risk PV. Additionally, emerging data suggest that early treatment is associated with higher rates of molecular responses, which might eventually enable time-limited therapy. Nonetheless, longer follow-up is needed to assess whether molecular responses associate with clinically meaningful outcome measures such as thrombosis and progression to myelofibrosis or AML. In this article, we provide an overview of the current and evolving treatment landscape of PV and outline our vision for a patient-centered, phlebotomy-free, treatment approach using time-limited, disease-modifying treatment modalities early in the disease course, which could ultimately affect the natural history of the disease.

Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia.

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).

Percutaneous treatment of mechanical mitral valve thrombosis.

A 75-year-old female was found to have mechanical mitral valve thrombosis complicated by severe mitral stenosis, pulmonary edema, and right heart failure. She was at prohibitive risk for surgical intervention. She did not tolerate thrombolysis due to bleeding. We performed percutaneous intervention with cerebral protection with subsequent restoration of mechanical mitral valve function, resolution of the mitral valve stenosis, and no neurologic complications.

Risk-based and individualised management of bleeding and thrombotic events in adults with primary immune thrombocytopenia (ITP).

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20-30 × 109 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient- and disease-related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient-centric approach. Currently, evidence-based recommendations and validated tools are lacking to support decision-making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk-based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

Managing Hemostasis in Space.

Human space travel requires exposure to weightlessness, ionizing radiation, isolation, and austerity. A recent report of internal jugular vein thrombosis in astronauts in low Earth orbit confirms that these exposures also affect vascular biology to influence diseases of thrombosis and hemostasis. This brief review summarizes the known influences of space travel on inflammation, blood coagulation, and the cardiovascular system and conceptualizes how they might combine to affect thrombosis and hemostasis. In the event of a major thrombotic or bleeding emergency, it is anticipated that the unique physiological influences of the space environment and logistical limitations of providing medical care in space would require a response that is unique from our current experience. We also look towards the future to discuss lessons learned from our current experiences on Earth and in space.

Comparison of pharmacological thrombolysis with mechanical thrombectomy in thrombosed arteriovenous fistulas and grafts: a systemic review and meta-analysis.

AIM: To compare the effectiveness and safety of pharmacological thrombolysis and mechanical thrombectomy. MATERIAL AND METHODS: This review was conducted in accordance with the PRISMA guidelines. Pooled proportions and subgroup analysis were calculated for primary and secondary patency rates, technical success, clinical success, major and minor complications rates. RESULTS: This systematic review identified a total of 6,492 studies of which 17 studies were included for analysis. A total of 1,089 patients comprising 451 (41.4 %) and 638 (58.6 %) patients who underwent thrombolysis and mechanical thrombectomy procedures, respectively, were analysed. No significant differences were observed between thrombolysis and mechanical thrombectomy procedures in terms of technical success, clinical success, major and minor complications rates, primary and secondary patency rates; however, subgroup analysis of overall arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) demonstrated a significantly higher rate of major complications within the AVF group (p=0.0248). CONCLUSION: The present meta-analysis suggests that pharmacological thrombolysis and mechanical thrombectomy procedures are similarly effective and safe; however, AVFs are subject to higher major complications compared to AVGs.

Plasma Fibrinogen Change as a Predictor of Major Bleeding During Catheter-Directed Thrombolysis.

BACKGROUND: Our primary objective was to determine the relationship between plasma fibrinogen levels (PFLs) and major bleeding complications during catheter-directed thrombolysis, including final, nadir, and change over time. Furthermore, we sought to evaluate additional predictors of bleeding outcomes, including duration of lysis and total dose of tissue plasminogen activator received. METHODS: In this multicenter retrospective cohort study, we reviewed all patients undergoing catheter-directed thrombolysis between January 2016 and August 2021. Patients undergoing thrombolysis for management of peripheral arterial or venous thromboses, as well as for submassive pulmonary embolism, were included. We examined the relationships between PFLs during catheter-directed lysis and the incidence of major bleeding-that is significant hemorrhage requiring transfusion, intracranial hemorrhage, or hemorrhage requiring adjunctive procedures. We also examined the duration of lysis and total lytic agent dose received to assess for association with major bleeding. RESULTS: A total of 438 patients underwent catheter-directed lysis from January 1, 2016 through August 21, 2021, with a major bleeding rate of 16%. Patients who experienced major bleeding were more likely to be older (P = 0.022), experience in-stent thrombosis (P = 0.041), or have thrombosis in a lower extremity vessel (P = 0.011). There was no association between the incidence of major bleeding and a nadir PFL of <150 mg/dL (P = 0.194). Those who experienced major bleeding complications had a significantly greater decrease in PFL from baseline to nadir. This was true for both absolute (P = 0.029) and relative (P = 0.034) PFL decrease. Only percent decrease remained a significant predictor when adjusting for age, thrombosis type, and thrombosis location (P = 0.041). The PFL changes that were the best predictors of major bleeding complications were an absolute decrease of 146 mg/dL, or a relative decrease of 47%, giving a sensitivity and specificity of 71% and 48%, respectively. If neither were true, the negative predictive value for major bleeding was 89% regardless of absolute PFL. CONCLUSIONS: In this large, multicenter cohort, there does not appear to be an association between absolute PFL and major bleeding during catheter-directed lysis. Specifically, the typical absolute threshold of < 150 mg/dL was not an independent predictor of major bleeding. There was an association between percent-change in plasma fibrinogen and major bleeding, which aligns with the underlying physiologic mechanism of fibrinogen degradation coagulopathy. Applying a so-called "50-150 Rule" to catheter-directed lysis may decrease bleeding complications. That is, continued lysis should be re-evaluated if PFL drops by ≥150 mg/dL or by ≥50% from baseline regardless of absolute PFL.

Ultrasound Combined With Continuous Microbubble Injection to Enhance Catheter-Directed Thrombolysis in Vitro and in Vivo.

OBJECTIVES: To investigate the influence of microbubble perfusion mode on catheter-directed thrombolysis (CDT), we evaluated the effect of two different types of microbubble perfusion modes (continuous injection versus bolus injection) on the thrombolytic efficacy of CDT in vitro and further assessed the effect of continuous microbubble injection on CDT in vivo. METHODS: In an in vitro experimental setup, 50 fresh bovine whole blood clots were randomized into five groups: ultrasound and continuous microbubble injection-enhanced CDT (US + cMB + CDT), ultrasound and bolus microbubble injection-enhanced CDT (US + bMB + CDT), US + CDT, US + cMB, and CDT. In a porcine femoral vein thrombosis model, 16 completely obstructive thrombi were randomly assigned to the CDT group and the US + cMB + CDT group, respectively. Thrombolysis rate, vascular recanalization rate, hematoxylin-eosin, and immunofluorescence staining were used to evaluate the thrombolytic effect in vitro and in vivo. RESULTS: In vitro, US + cMB + CDT group resulted in a significantly higher thrombolysis rate compared with the other four groups (P < .05). Meanwhile, this group also demonstrated a looser clot structure and more disrupted fibrin structures. In vivo, US + cMB + CDT contributed to a significantly higher vascular recanalization rate compared with CDT (87.50% versus 25.00%, P < .05). CONCLUSIONS: US + cMB + CDT was more effective than US + bMB + CDT in thrombolysis, and ultrasound combined with continuous microbubble injection could enhance the thrombolytic efficacy of CDT.

Evaluation and Management of Mechanical Heart Valve Dysfunction and Thrombosis.

PURPOSE OF REVIEW: Dysfunction and thrombosis of mechanical heart valves, although uncommon, represents a challenge that requires multidisciplinary expertise for diagnosis and management. The aim of this review is to summarize strengths and weaknesses of diagnostic methods and therapeutic strategies for this uncommon but potentially life-threatening pathology. RECENT FINDINGS: Expeditious diagnosis of mechanical valve thrombosis and exclusion of other diagnostic considerations, often with incorporation of multimodality imaging, can inform the best treatment strategy. Presentation of mechanical valve thrombosis can be asymptomatic or can include heart failure, life-threatening embolic events, or cardiogenic shock. Echocardiography, fluoroscopy and computed tomography are important in the evaluation of mechanical valve dysfunction. Therapeutic strategies for thrombosis include anticoagulation, systemic thrombolysis, and surgery. Choice of treatment depends on multiple factors including thrombus size, degree of valve dysfunction, clinical presentation, and available surgical expertise.

Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus: State of art and future perspectives.

BACKGROUND: Despite advances in the diagnosis of patients with hepatocellular carcinoma (HCC), 70%-80% of patients are diagnosed with advanced stage disease. Portal vein tumor thrombus (PVTT) is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated. DATA SOURCES: A systematic search of MEDLINE (PubMed), Embase, Cochrane Library and Database for Systematic Reviews (CDSR), Google Scholar, and National Institute for Health and Clinical Excellence (NICE) databases until December 2022 was conducted using free text and MeSH terms: hepatocellular carcinoma, portal vein tumor thrombus, portal vein thrombosis, vascular invasion, liver and/or hepatic resection, liver transplantation, and systematic review. RESULTS: Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy. Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus, accurate identification of the subgroups of patients who may benefit from resection, as well as meticulous surgical technique. This review addressed five specific areas: (a) formation of PVTT; (b) classifications of PVTT; (c) controversies related to clinical guidelines; (d) surgical treatments versus non-surgical approaches; and (e) characterization of surgical techniques correlated with classifications of PVTT. CONCLUSIONS: Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Late device-related thrombus associated with occult malignancy years after left atrial appendage closure.

INTRODUCTION: The use of Left Atrial Appendage (LAA) occluder devices has been on the rise in patients with atrial fibrillation. Studies regarding the long-term risks of occluder devices remain sparse. MATERIALS & METHODS: In this brief report, we discuss the unusual case of an 85-year-old female with long-term complication from Left Atrial Appendage (LAA) closure: Device-Related Thrombus (DRT) about two years after insertion. RESULTS: Compared to the expected stroke rate without anticoagulation, patients with DRT on their LAAO device still had a 28 % relative reduction in ischemic stroke. This suggests that these strokes may have emanated from alternate etiologies other than the DRT. CONCLUSIONS: Patients with active or known history of cancer appears to have a higher risk of DRT. More data is needed on this topic to augment awareness and understanding of LAAO complications and DRT management strategies.

[Progress in the diagnose and treatment of pulmonary arterial thrombosis in situ].

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

A Spiky Silver-Iron Oxide Nanoparticle for Highly Efficient Targeted Photothermal Therapy and Multimodal Imaging of Thrombosis.

Thrombosis and its complications are responsible for 30% of annual deaths. Limitations of methods for diagnosing and treating thrombosis highlight the need for improvements. Agents that provide simultaneous diagnostic and therapeutic activities (theranostics) are paramount for an accurate diagnosis and rapid treatment. In this study, silver-iron oxide nanoparticles (AgIONPs) are developed for highly efficient targeted photothermal therapy and imaging of thrombosis. Small iron oxide nanoparticles are employed as seeding agents for the generation of a new class of spiky silver nanoparticles with strong absorbance in the near-infrared range. The AgIONPs are biofunctionalized with binding ligands for targeting thrombi. Photoacoustic and fluorescence imaging demonstrate the highly specific binding of AgIONPs to the thrombus when functionalized with a single chain antibody targeting activated platelets. Photothermal thrombolysis in vivo shows an increase in the temperature of thrombi and a full restoration of blood flow for targeted group but not in the non-targeted group. Thrombolysis from targeted groups is significantly improved (p < 0.0001) in comparison to the standard thrombolytic used in the clinic. Assays show no apparent side effects of AgIONPs. Altogether, this work suggests that AgIONPs are potential theranostic agents for thrombosis.

How I treat dysfibrinogenemia.

Congenital dysfibrinogenemia (CD) is caused by structural changes in fibrinogen that modify its function. Diagnosis is based on discrepancy between decreased fibrinogen activity and normal fibrinogen antigen levels and is confirmed by genetic testing. CD is caused by monoallelic mutations in fibrinogen genes that lead to clinically heterogenous disorders. Most patients with CD are asymptomatic at the time of diagnosis, but the clinical course may be complicated by a tendency toward bleeding and/or thrombosis. Patients with a thrombosis-related fibrinogen variant are particularly at risk, and, in such patients, long-term anticoagulation should be considered. Management of surgery and pregnancy raise important and difficult issues. The mainstay of CD treatment remains fibrinogen supplementation. Antifibrinolytic agents are part of the treatment in some specific clinical settings. In this article, we discuss 5 clinical scenarios to highlight common clinical challenges. We detail our approach to establishing a diagnosis of CD and discuss strategies for the management of bleeding, thrombosis, surgery, and pregnancy.

A Bayesian network meta-analysis for acute thrombosis after lower extremity artery endovascular treatment.

BACKGROUND: Various endovascular treatment devices have been widely used in the lower extremity arterial disease (LEAD). Their patency efficiency for target lesions has been well studied and reported. Comparison of the risk of acute thrombosis events between the different endovascular treatment devices is unclear. AIMS: To rank the risk of acute thrombosis events when bare metal stents (BMSs), covered stents (CSs), drug-eluting stents (DESs), drug-coated balloons (DCBs), and conventional percutaneous transluminal balloon angioplasty (PTA) are used to treat LEAD through Bayesian network meta-analysis. METHODS: We performed a network meta-analysis of randomized controlled trials comparing the risk of 1-year postoperative acute thrombosis between BMSs, CSs, DESs, DCBs, and PTA for treating LEAD. Bayesian random models were used for pooled endovascular treatment modality comparisons. We ranked these treatment modalities via the Bayesian method according to their surface under the cumulative ranking curve (SUCRA) and estimated probabilities. RESULTS: Nineteen studies (38 study arms; 2758 patients) were included. The Bayesian network ranking of treatments indicated that DCB had the lowest risk of acute thrombosis, PTA had the second-lowest risk of thrombosis, and CS, BMS, and DES had the highest risk of thrombosis. Regarding the treatment efficacy, the OR values of the loss of primary patency were significantly lower for DCB (OR = 0.44, 95% CI: 0.30-0.62), DES (OR = 0.36, 95% CI: 0.14-0.94), and CS (OR = 0.31, 95% CI: 0.18,0.56) than for PTA. When BMS was used as a reference, only the OR for CS was significantly lower (OR = 0.41, 95% CI = 0.21-0.82). Correspondingly, the Bayesian ranking of treatments from better to worse target lesion primary patency was CS, DES, DCB, BMS, and PTA. CONCLUSION: With the available research evidence and according to the network analysis ranking, DES appears to have the highest risk of acute thrombosis and DCB appears to have the lowest risk.

Left atrial disc device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder: A case series.

Device thromboses after patent foramen ovale (PFO) and atrial septal defect (ASD) closure are rare but serious complications. They have been reported in different devices of virtually all manufacturers. Here, we report three cases of left atrial device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder (GSO) in our recent institutional experience. All patients were symptomatic with new-onset neurological impairments and evidence of cerebral thromboembolism. Device thromboses have occurred despite antiplatelet therapy in two patients and moreover were observed late, at approximately 2 years after implantation, in two patients. One device was surgically explanted while in two cases, thrombi completely resolved with initiated anticoagulation. All patients had a favorable neurological recovery. Our observations suggest that regular follow-up echocardiography beyond 6 months after device implantation might be advisable in patients with GSO devices to rule out late device thromboses. More long-term follow-up data considering safety and late complications of contemporary PFO and ASD devices is required to establish confident evidence-based recommendations on long-term follow-up management and antithrombotic therapy regimen after PFO and ASD closure.

Cleaner XT Rotational Thrombectomy: An Efficacious Endovascular Technique for Salvage of Thrombosed Arteriovenous Access and a 12 Month Outcome Analysis.

PURPOSE: This study aims to describe an efficacious method using Cleaner XT rotational thrombectomy with catheter-directed thrombolysis and drug-eluting balloon angioplasty for the salvage of thrombosed arteriovenous fistulae and grafts. MATERIALS AND METHODS: Retrospective analysis of all patients with thrombosed hemodialysis accesses who underwent endovascular salvage using the Cleaner XT rotational thrombectomy system at a single institution between June 2019 and September 2020 was performed. Patency was presented as Kaplan-Meier survival curves, and regression analysis was performed to examine predictors of postintervention primary patency and assisted primary patency based on Cox proportional-hazards model. RESULTS: Thirty-four patients with thrombosed accesses underwent Cleaner XT rotational thrombectomy between June 2019 and September 2020. Technical and clinical success were both 100%. Mean procedure time was 62 ± 20 minutes. Mean postintervention primary patency time was 152 ± 51 days; 30, 90, 180, and 365 day postintervention primary patency rates were 89%, 80%, 68%, and 56%, respectively. Mean postintervention-assisted primary patency time was 157 ± 59 days; 30, 90, 180, and 365 day postintervention-assisted primary patency rates were 91%, 82%, 71%, and 59%, and 180 and 365 day secondary patency rates were 97.2% and 94.4%, respectively. CONCLUSION: The Cleaner XT rotational thrombectomy device demonstrates excellent clinical and technical success rates, with good patency results at all time points up to 12 months postintervention.

IN.PACT AV Access Randomized Trial of Drug-Coated Balloons for Dysfunctional Arteriovenous Fistulae: Clinical Outcomes through 36 Months.

PURPOSE: To present the 36-month outcomes of the prospective randomized IN.PACT AV Access study of participants with obstructive de novo or restenotic native upper extremity arteriovenous dialysis fistula lesions treated with drug-coated balloon (DCBs) or standard percutaneous transluminal angioplasty (PTA) following successful high-pressure PTA. MATERIALS AND METHODS: Participants at 29 international sites were randomized 1:1 to receive an IN.PACT AV DCB (n = 170) or undergo PTA (n = 160). The outcomes through 36 months included target lesion primary patency (TLPP) and access circuit primary patency (ACPP) (composites of clinically driven target lesion or access circuit revascularization and/or access circuit thrombosis), number of reinterventions, and serious adverse events involving the access circuit. RESULTS: TLPP was 52.1% in the DCB group compared with 36.7% in the PTA group through 24 months and 43.1% in the DCB group compared with 28.6% in the PTA group through 36 months (both log-rank P < .001). ACPP was 39.4% in the DCB group compared with 25.3% in the PTA group through 24 months and 26.4% in the DCB group compared with 16.6% in the PTA group through 36 months (both log-rank P < .001). Cumulative incidence of access circuit thrombosis through 36 months was 8.2% in the DCB group compared with 18.3% in the PTA group (log-rank P = .040). Cumulative incidence of mortality through 36 months was 26.6% in the DCB group compared with 30.8% in the PTA group (log-rank P = .71). CONCLUSIONS: This study demonstrated superior TLPP and ACPP with DCBs compared with PTA, with no difference in mortality through 3 years. Access circuit thrombosis was statistically significantly higher in the PTA group at 3 years.