Iliac artery endofibrosis: diagnostic dilemna and treatment options.

BACKGROUND: External iliac artery endofibrosis (EIAE) is an uncommon pathology, predominantly occurring in cyclists, caused by thickening of the external iliac artery intima. Symptoms are exercise-dependent and typically consist of pain, muscle cramps and loss of strength in the affected limb at (sub)maximal effort. As other musculo-skeletal as well as conditional problems might cause similar complaints diagnosis is not always easy or straightforward. CASE SUMMARY AND DISCUSSION: We reviewed four cases of (semi-)professional cyclists referred to our department in 2021 because of suspicion of EIAE. In all symptoms only occurred at (sub)maximal effort. All had lowering of ABI on the affected side at a dynamic stress test on the bike. Imaging using CTA, MRA or dynamic angiogram was abnormal in all patients, showing signs suspicious for endofibrosis but of different kind and at different locations. Open surgical repair was performed in all cases by a procedure tailored to the type of lesion. Two patients were treated by a saphenous vein patch angioplasty, in one patient a shortening of the vessel and end-to-end anastomosis was performed and in the fourth patient a spiral saphenous vein graft bypass was placed. Postoperative course was uneventful and exercise was resumed after four weeks in all patients. CONCLUSION: Correct diagnosis is essential in the treatment of EIAE. A complete and multidisciplinary pathway should be followed to distinguish vascular from non-vascular causes. Correct lesion localization is crucial and besides CTA or MRA, more sophisticated techniques such as dynamic angiography or intravascular ultrasound might be needed.

A Proficiency Based Stepwise Endovascular Curricular Training (PROSPECT) Program Enhances Operative Performance in Real Life: A Randomised Controlled Trial.

OBJECTIVES: Healthcare evolution requires optimisation of surgical training to provide safe patient care. Operating room performance after completion of proficiency based training in vascular surgery has not been investigated. DESIGN: A randomised controlled trial evaluated the impact of a Proficiency based Stepwise Endovascular Curricular Training program (PROSPECT) on the acquisition of endovascular skills and the transferability of these skills to real life interventions. MATERIALS: All subjects performed two endovascular interventions treating patients with symptomatic iliac and/or superficial femoral artery stenosis under supervision. Primary outcomes were technical performances (Global Rating Scale [GRS]; Examiner Checklist), operative metrics, and patient outcomes, adjusted for case difficulty and trainee experience. Secondary outcomes included knowledge and technical performance after 6 weeks and 3 months. METHODS: Thirty-two general surgical trainees were randomised into three groups. Besides traditional training, the first group (n = 11) received e-learning and simulation training (PROSPECT), the second group (n = 10) only had access to e-learning, while controls (n = 11) did not receive supplementary training. RESULTS: Twenty-nine trainees (3 dropouts) performed 58 procedures. Trainees who completed PROSPECT showed superior technical performance (GRS 39.36 ± 2.05; Checklist 63.51 ± 3.18) in real life with significantly fewer supervisor takeovers compared with trainees receiving e-learning alone (GRS 28.42 ± 2.15; p = .001; Checklist 53.63 ± 3.34; p = .027) or traditional education (GRS 23.09 ± 2.18; p = .001; Checklist 38.72 ± 3.38; p = .001). Supervisors felt more confident in allowing PROSPECT trained physicians to perform basic (p = .006) and complex (p = .003) procedures. No differences were detected in procedural parameters (such as fluoroscopy time, DAP, procedure time, etc.) or complications. Proficiency levels were maintained up to 3 months. CONCLUSIONS: A structured, stepwise, proficiency based endovascular curriculum including e-learning and simulation based training should be integrated early into training programs to enhance trainee performance.

A Multicentre Trial of Patient specific Rehearsal Prior to EVAR: Impact on Procedural Planning and Team Performance.

OBJECTIVE: Patient specific rehearsal (PsR) prior to endovascular aneurysm repair (EVAR) enables the endovascular team to practice and evaluate the procedure prior to treating the real patient. This multicentre trial aimed to evaluate the utility of PsR prior to EVAR as a pre-operative planning and briefing tool. MATERIAL AND METHODS: Patients with an aneurysm suitable for EVAR were randomised to pre-operative or post-operative PsR. Before and after the PsR, the lead implanter completed a questionnaire to identify any deviation from the initial treatment plan. All team members completed a questionnaire evaluating realism, technical issues, and human factor aspects pertinent to PsR. Technical and human factor skills, and technical and clinical success rates were compared between the randomised groups. RESULTS: 100 patients were enrolled between September 2012 and June 2014. The plan to visualise proximal and distal landing zones was adapted in 27/50 (54%) and 38/50 (76%) cases, respectively. The choice of the main body, contralateral limb, or iliac extensions was adjusted in 8/50 (16%), 17/50 (34%), and 14/50 (28%) cases, respectively. At least one of the abovementioned parameters was changed in 44/50 (88%) cases. For 100 EVAR cases, 199 subjective questionnaires post-PsR were completed. PsR was considered to be useful for selecting the optimal C-arm angulation (median 4, IQR 4-5) and was recognised as a helpful tool for team preparation (median 4, IQR 4-4), to improve communication (median 4, IQR 3-4), and encourage confidence (median 4, IQR 3-4). Technical and human factor skills and technical and initial clinical success rates were similar between the randomisation groups. CONCLUSION: PsR prior to EVAR has a significant impact on the treatment plan and may be useful as a pre-operative planning and briefing tool. Subjective ratings indicate that this technology may facilitate planning of optimal C-arm angulation and improve non-technical skills. TRIAL REGISTRATION: URL://www.clinicaltrials.gov. Unique identifier: NCT01632631.

Systematic review of e-learning for surgical training.

BACKGROUND: Internet and software-based platforms (e-learning) have gained popularity as teaching tools in medical education. Despite widespread use, there is limited evidence to support their effectiveness for surgical training. This study sought to evaluate the effectiveness of e-learning as a teaching tool compared with no intervention and other methods of surgical training. METHODS: A systematic literature search of bibliographical databases was performed up to August 2015. Studies were included if they were RCTs assessing the effectiveness of an e-learning platform for teaching any surgical skill, compared with no intervention or another method of training. RESULTS: From 4704 studies screened, 87 were included with 7871 participants enrolled, comprising medical students (52 studies), trainees (51 studies), qualified surgeons (2 studies) and nurses (6 studies). E-learning tools were used for teaching cognitive (71 studies), psychomotor (36 studies) and non-technical (8 studies) skills. Tool features included multimedia (84 studies), interactive learning (60 studies), feedback (27 studies), assessment (26 studies), virtual patients (22 studies), virtual reality environment (11 studies), spaced education (7 studies), community discussions (2 studies) and gaming (2 studies). Overall, e-learning showed either greater or similar effectiveness compared with both no intervention (29 and 4 studies respectively) and non-e-learning interventions (29 and 22 studies respectively). CONCLUSION: Despite significant heterogeneity amongst platforms, e-learning is at least as effective as other methods of training.

Transatlantic Multispecialty Consensus on Fundamental Endovascular Skills: Results of a Delphi Consensus Study.

OBJECTIVES: The aim of this study was to establish a consensus on Fundamental Endovascular Skills (FES) for educational purposes and development of training curricula for endovascular procedures. The term "Fundamental Endovascular Skills" is widely used; however, the current literature does not explicitly describe what skills are included in this concept. Endovascular interventions are performed by several specialties that may have opposing perspectives on these skills. METHODS: A two round Delphi questionnaire approach was used. Experts from interventional cardiology, interventional radiology, and vascular surgery from the United States and Europe were invited to participate. An electronic questionnaire was generated by endovascular therapists with an appropriate educational background but who would not participate in subsequent rounds. The questionnaire consisted of 50 statements describing knowledge, technical, and behavioral skills during endovascular procedures. Experts received the questionnaires by email. They were asked to rate the importance of each skill on a Likert scale from 1 to 5. A statement was considered fundamental when more than 90% of the experts rated it 4 or 5 out of 5. RESULTS: Twenty-three of 53 experts invited agreed to participate: six interventional radiologists (2 USA, 4 Europe), 10 vascular surgeons (4 USA, 6 Europe), and seven interventional cardiologists (4 USA, 3 Europe). There was a 100% response rate in the first round and 87% in the second round. Results showed excellent consensus among responders (Cronbach's alpha = .95 first round; .93 second round). Ninety percent of all proposed skills were considered fundamental. The most critical skills were determined. CONCLUSIONS: A transatlantic multispecialty consensus was achieved about the content of "FES" among interventional radiologists, interventional cardiologists, and vascular surgeons from Europe and the United States. These results can serve as directive principles for developing endovascular training curricula.

Standardized definitions and clinical endpoints in trials investigating endovascular repair of aortic dissections.

OBJECTIVES: Endovascular therapy is a rapidly expanding option for the treatment of patients with aortic dissection (AD) and various studies have been published. These trials, however, are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. METHODS: The DEFINE Group is a collaborative effort of an ad hoc multidisciplinary team from various specialties involved in AD therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in trials for endovascular therapy of various vascular pathologies. In this project, which started in December 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. RESULTS: These efforts resulted in the present document containing proposed baseline and endpoint definitions for clinical and morphological outcomes. Although the consensus has inevitably included certain arbitrary consensus choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSIONS: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in endovascular AD therapy as well as for regulatory purposes.

DISSECT: a new mnemonic-based approach to the categorization of aortic dissection.

OBJECTIVE/BACKGROUND: Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. METHODS AND RESULTS: The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. CONCLUSION: In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process.

Patient-specific rehearsal prior to EVAR: a pilot study.

OBJECTIVES: This study aims to evaluate feasibility, face validity, influence on technical factors and subjective sense of utility of patient-specific rehearsal (PsR) prior to endovascular aortic aneurysm repair (EVAR). DESIGN: A prospective, multicentre pilot study. METHODS: Patients suitable for EVAR were enrolled and a three-dimensional (3D) model of the patient's anatomy was generated. Less than 24 h prior to the real case, rehearsals were conducted in the laboratory or clinical angiosuite. Technical metrics were recorded during both procedures. A subjective questionnaire was used to evaluate realism, technical and human factor aspects (scale 1-5). RESULTS: Ten patients were enrolled. In one case, the treatment plan was altered based on PsR. In 7/9 patients, the rehearsal significantly altered the optimal C-arm position for the proximal landing zone and an identical fluoroscopy angle was chosen in the real procedure. All team members found the rehearsal useful for selecting the optimal fluoroscopy angle (median 4). The realism of the EVAR procedure simulation was rated highly (median 4). All team members found the PsR useful to prepare the individual team members and the entire team (median 4). CONCLUSIONS: PsR for EVAR permits creation of realistic case studies. Subjective evaluation indicates that it may influence optimal C-arm angles and be valuable to prepare the entire team. A randomised controlled trial (RCT) is planned to evaluate how this technology may influence technical and team performance, ultimately leading to improved patient safety.

COPD is associated with reduced pulmonary interstitial expression of pentraxin-3.

Pentraxin (PTX)3 is involved in antimicrobial defence, apoptotic cell clearance and extracellular matrix stability. As these processes are altered in chronic obstructive pulmonary disease (COPD), we aimed to investigate PTX3 expression in patients with this disease. PTX3 expression was quantified by immunohistochemical staining of lung tissue from never-smokers, smokers without COPD, and in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II and III-IV. mRNA expression was examined in total lung tissue by quantitative RT-PCR. PTX3 concentration was measured in induced sputum and plasma by ELISA. PTX3 is mainly localised in the interstitium of the small airways and alveolar walls. There were no significant differences in pulmonary, sputum and plasma PTX3 expression between study groups. However, PTX3 expression in small airways correlated significantly with forced expiratory volume in 1 s (r = 0.35, p = 0.004). In the alveolar walls, PTX3 expression correlated significantly with carbon monoxide transfer coefficient (r = 0.28, p = 0.04). In sputum, PTX3 levels were highly correlated with the number of neutrophils. Finally, systemic levels of PTX3 tended to be lower in severe COPD compared with mild COPD. In COPD, airflow limitation and reduced transfer coefficient for carbon monoxide are associated with lower pulmonary interstitial expression of PTX3.

Role of patient-specific virtual reality rehearsal in carotid artery stenting.

BACKGROUND: Recent advances in simulation science permit patient-specific rehearsal of endovascular stenting procedures. This study aimed to evaluate how effectively real interventions are replicated by patient-specific rehearsal technology, and to assess its value as a preparatory tool for the interventionalist and the operating team. METHODS: All patients deemed candidates for carotid artery stenting procedures with suitable computed tomography images were enrolled. Each team member rehearsed the virtual procedure in the laboratory, simulated operating theatre or angiography suite environment immediately before treating the real patient. Dexterity and qualitative metrics were recorded. Subjective questionnaires used a Likert scale from 1 (poor) to 5 (excellent). RESULTS: Of 18 patients, three were excluded. In 11 of 15 and 13 of 15 patients respectively endovascular tool use and fluoroscopy angles were identical during rehearsal and the real procedure. In a third of patients, the simulator did not adequately predict difficulties in cannulating the stenotic internal or common carotid arteries. The procedure realism, value in evaluating the case, increase in efficiency in tool use, and potential to increase communication, confidence and team performance were all rated highly (4 of 5). CONCLUSION: Patient-specific rehearsal was rated highly for both face and content validity. Access strategy, endovascular material use and angiographic imaging were all replicated effectively, although certain biomechanical vessel properties seemed to be replicated to a lesser degree. Patient-specific rehearsal constitutes a unique tool that may help tailor endovascular material choice, and optimize the preoperative preparation of the interventionalist and team.

Diagnosing COVID-19; towards a feasible COVID-19 rule-out protocol.

INTRODUCTION: We present the results of the COVID-19 rule-out protocol at Ghent University Hospital, a step-wise testing approach which included repeat NFS SARS-CoV-2 rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with BAL to confirm or rule-out SARS-CoV-2 infection in patients admitted with symptoms suggestive of COVID-19. RESULTS: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms suspect for COVID-19 were admitted. The initial NFS for SARS-CoV-2 rRT-PCR yielded 66.9%, the second NFS 25.4% and bronchoscopy with BAL 5.9% of total COVID-19 diagnoses. In the BAL fluid, other respiratory pathogens were detected in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing at the time around BAL sampling showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group. Follow-up serology showed 100% COVID-19 positivity in the COVID-19 positive group and 100% IgG negativity in the COVID-19 negative group. CONCLUSION: In our experience, bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Retrospective analysis of antibody development in this selected group of patients suggests that the implementation of serological assays in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.

Efficient implementation of patient-specific simulated rehearsal for the carotid artery stenting procedure: part-task rehearsal.

OBJECTIVE(S): Patient-specific simulated rehearsal (PsR) is a technological advance within the domain of endovascular virtual reality (VR) simulation. It allows incorporation of patient-specific computed tomography Digital Imaging and Communications in Medicine (CT DICOM) data into the simulation and subsequent rehearsal of real patient cases. This study aimed to evaluate whether a part-task rehearsal (PTr) of a carotid artery stenting procedure (CAS) on a VR simulator is as effective as a full-task (FTr) preoperative run through. METHODS: Medical trainees were trained in the CAS procedure and randomised to a PTr or FTr of a challenging CAS case (Type-II arch). PTr consisted of 30 min of repeated catheterisations of the common carotid artery (CCA). Thereafter, both groups performed the CAS procedure in a fully functional simulated operating suite (SOS) with an interventional team. Technical performances were assessed using simulator-based metrics and expert ratings. Other aspects of performance were assessed using the Non-Technical Skills for Surgeons (NOTSS) scoring. RESULTS: Twenty trainees were evenly randomised to either PTr or FTr. No differences in performance were seen except for the total time the embolic protection device (EPD) was deployed (9.4 min for the PT vs. 8.1 min for the FT, p = 0.02). Total time (26.3 vs. 25.5 min, p = 0.94), fluoroscopy time (15.8 vs. 14.4 min, p = 0.68), number of roadmaps (10.5 vs. 11.0, p = 0.54), amount of contrast (53.5 vs. 58.0 ml, p = 0.33), time to deploy the EPD (0.9 vs. 0.8 min, p = 0.31) and time to catheterise the CCA (9.2 vs. 8.9 min, p = 0.94) were similar. Qualitative performances as measured by expert ratings (score 24 vs. 24, p = 0.49) and NOTSS (p > 0.05 for all categories) were also comparable. CONCLUSIONS: Part- and full-task rehearsals are equally effective with respect to the operative performance of a simulated CAS intervention. This finding makes a patient-specific rehearsal more efficient and may increase the feasibility of implementation of this technology into medical practice.

Patient-specific endovascular simulation influences interventionalists performing carotid artery stenting procedures.

OBJECTIVE: The ability to perform patient-specific simulated rehearsal of complex endovascular interventions is a technological advance with potential benefits to patient outcomes. This study aimed to evaluate whether patient-specific rehearsal of a carotid artery stenting (CAS) procedure has an influence on tool selection and the use of fluoroscopy. METHODS: Following case note and computed tomography (CT) angiographic review of a real patient case, subjects performed the CAS procedure on a virtual reality simulator. Endovascular tool requirements and fluoroscopic angles were evaluated with a pre- and post-case questionnaire. Participants also rated the simulation from 1 (poor) to 5 (excellent). RESULTS: Thirty-three endovascular physicians with varying degrees of CAS experience were recruited: inexperienced (5-20 CAS procedures) n = 11, moderately (21-50 CAS procedures) n = 7 or highly experienced (>50 CAS procedures) n = 15. For all participants, 96 of a possible 363 changes (26%) were observed from pre- to post-case questionnaires. This was most notable for optimal fluoroscopy C-arm position 15/33 (46%), choice of selective catheter 13/33 (39%), choice of sheath or guiding catheter 11/33 (33%) and balloon dilatation strategy 10/33 (30%). Experience with the CAS procedure did not influence the degree of change significantly (p > 0.05), and all groups exhibited a considerable modification in tool and fluoroscopy preference. The model was considered realistic and useful as a tool to practice a real case (median score 4/5). CONCLUSION: Patient-specific simulated rehearsal of a complex endovascular procedure strongly influences tool selection and fluoroscopy preferences for the real case. Further research has to evaluate how this technology may transfer from in vitro to in vivo and if it can reduce the radiation dose and the number of endovascular tools used and improve outcomes for patients in the clinical setting.

Training with simulation versus operative room attendance.

Reduced training times, increasing complexity of endovascular and open vascular interventions and concerns for patient's safety have necessitated a modernisation in surgical training. A more strategic approach is required to facilitate the acquisition of surgical skills outside the operating room and to minimize the risks to patients as surgeons develop their technical expertise. Virtual reality simulation has been proposed as a means to train and objectively assess technical endovascular performance without risks to patient safety. This article reviews the evidence and the limitations for this adjunctive tool, the implementation in current training programmes and future applications to maintain the highest standards of care for treatment of vascular disease.

Plasmacytoid dendritic cells in pulmonary lymphoid follicles of patients with COPD.

Plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells with antiviral and tolerogenic capabilities. Viral infections and autoimmunity are proposed to be important mechanisms in the pathogenesis of chronic obstructive pulmonary disease (COPD). The study aimed to quantify blood dendritic cell antigen 2-positive pDCs in lungs of subjects with or without COPD by immunohistochemistry and flow cytometry, combined with the investigation of the influence of cigarette smoke extract (CSE) on the function of pDCs in vitro. pDCs were mainly located in lymphoid follicles, a finding compatible with their expression of lymphoid homing chemokine receptors CXCR3 and CXCR4. pDC accumulated in the lymphoid follicles and in lung digests of patients with mild to moderate COPD, compared with smokers without airflow limitation and patients with COPD Global Initiative for Chronic Obstructive Lung disease (GOLD) stage III-IV. Exposing maturing pDC of healthy subjects to CSE in vitro revealed an attenuation of the expression of co-stimulatory molecules and impaired interferon-α production. Maturing pDC from patients with COPD produced higher levels of tumour necrosis factor (TNF)-α and interleukin (IL)-8 compared to pDC from healthy subjects. CSE significantly impairs the antiviral function of pDCs. In COPD, a GOLD stage dependent accumulation of pDC in lymphoid follicles is present, combined with an enhanced production of TNF-α and IL-8 by maturing pDCs.

Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.

OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting. METHODS: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification). RESULTS: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.