Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.

BACKGROUND: Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown. METHODS: ASPEN-COVID-19 was an international, randomized, open-label, active comparator clinical trial with blinded end point adjudication. Hospitalized patients with COVID-19 and elevated D-dimer levels were randomized 1:1:2 to lower or higher dose rNAPc2 on days 1, 3, and 5 followed by heparin on day 8 or to heparin per local standard of care. In comparisons of the pooled rNAPc2 versus heparin groups, the primary safety end point was major or nonmajor clinically relevant International Society of Thrombosis and Haemostasis bleeding through day 8. The primary efficacy end point was proportional change in D-dimer concentration from baseline to day 8, or discharge if before day 8. Patients were followed for 30 days. RESULTS: Among 160 randomized patients, median age was 54 years, 43.1% were female, and 38.8% had severe baseline COVID-19. There were no significant differences between rNAPc2 and heparin in bleeding or other safety events. Overall, median change in D-dimer was -16.8% (interquartile range, -45.7 to 36.8; P=0.41) with rNAPc2 treatment and -11.2% (-36.0 to 34.4; P=0.91) with heparin (Pintergroup=0.47). In prespecified analyses, in severely ill patients, D-dimer levels tended to increase more within the heparin (median, 29.0% [-14.9 to 145.2]; P=0.02) than the rNAPc2 group (median, 25.9% [-49.1 to 136.4]; P=0.14; Pintergroup=0.96); in mildly ill patients, D-dimer levels were reduced within each group with a numerically greater reduction with rNAPc2 versus heparin (rNAPc2 median, -32.7% [-44.7 to 4.3]; P=0.007 and heparin median, -16.8% [-36.0 to 0.5]; P=0.008, Pintergroup=0.34). CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04655586.

Rivaroxaban in Peripheral Artery Disease after Revascularization.

BACKGROUND: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain. METHODS: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome. RESULTS: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007). CONCLUSIONS: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).

Comparison Study of Iliac Branch Endoprosthesis when Used on and off Label.

BACKGROUND: The aim of this study is to compare how instructions for use (IFU) affected perioperative and intermediate term outcomes for common iliac artery aneurysms (CIAA) treated with the Gore Excluder iliac branch endoprosthesis (IBE). METHODS: A retrospective analysis was performed of all patients treated at two affiliated academic centers from September 2016 to May 2020. Outcomes were compared between IFU and nonIFU IBE cases. Criteria for nonIFU included: (1) use with a nonGore aortic endoprosthesis (n = 10), (2) isolated IBE (n = 3), and (3) requiring nondedicated covered stents for additional extension into a more suitable landing zone in the ipsilateral internal iliac artery or one of its branches (n = 11). Perioperative and intermediate term data were collected for both groups. The primary end points were free from the major adverse event (MAE) at 30 days and primary effectiveness at 1 year. RESULTS: A total of 51 CIAA (39 patients) were treated with an IBE. Overall, 15 patients were treated under IFU and 24 under nonIFU. The IFU group mean age was older (72 vs. 67 years, P = 0.03), and males (97%) were primarily treated. Comorbidities were similar except nonIFU had more patients with previous endovascular abdominal aortic aneurysm repair on presentation (0 vs. 4 cases, P = 0.04). Procedure (178 vs. 264 min, P = 0.02) and fluoroscopy (52 vs. 74 min, P = 0.04) times were longer in the nonIFU group. Technical success was 100% for both groups, and there was no difference in device related reintervention at 30 days (0 vs. 1, P = 0.44). There was no MAE in either group at 30 days. Intervention for any endoleak was similar between the groups (2 vs. 3, P = 0.94). Percent CIAA sac regression was similar between the groups (19% vs. 18%, P = 0.21). There was no difference for primary effectiveness at 1 year (93% vs. 92%, P = 0.85). There was one death per group at one year not related to an aortic or iliac cause. CONCLUSIONS: In properly selected patients with complex anatomy, IBE can be used with nondedicated aortic and internal iliac components with good early term outcomes.

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. METHODS: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. RESULTS: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). CONCLUSIONS: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Etiology and outcomes of amputation in patients with peripheral artery disease in the EUCLID trial.

OBJECTIVE: Amputation remains a frequent and feared outcome in patients with peripheral artery disease (PAD). Although typically characterized as major or minor on the extent of tissue loss, the etiologies and outcomes after amputation by extent are not well-understood. In addition, emerging data suggest that the drivers and outcomes of amputation in patients with PAD may differ in those with and without diabetes mellitus (DM). METHODS: The EUCLID trial randomized 13,885 patients with symptomatic PAD, including 5345 with concomitant diabetes, to ticagrelor or clopidogrel and followed them for long-term outcomes. Amputations were prospectively reported by trial investigators. Their primary and contributing drivers were adjudicated using safety data, including infection, ischemia, or multifactorial etiologies. Outcomes following major and minor amputations were analyzed, including recurrent amputation, major adverse limb events, adverse cardiovascular events, and mortality. Multivariable logistic regression models were used to identify independent predictors of minor amputations. Analyses were performed overall and stratified by the presence or absence of DM at baseline. RESULTS: Of the patients randomized, 398 (2.9%) underwent at least one lower extremity nontraumatic amputation, for a total of 511 amputations (255 major and 256 minor) over a median of 30 months. A history of minor amputation was the strongest independent predictor for a subsequent minor amputation (odds ratio, 7.29; 95% confidence interval, 5.17-10.30; P < .001) followed by comorbid DM (odds ratio, 4.60; 95% confidence interval, 3.16-6.69; P < .001). Compared with patients who had a major amputation, those with a minor amputation had similar rates of subsequent major amputation (12.2% vs 13.6%), major adverse limb events (15.1% vs 14.9%), and major adverse cardiovascular events (17.6% vs 16.3%). Ischemia alone was the primary driver of amputation (51%), followed by infection alone (27%), and multifactorial etiologies (22%); however, infection was the most frequent driver in those with DM (58%) but not in those without DM (15%). CONCLUSIONS: Outcomes after amputation remain poor regardless of whether they are categorized as major or minor. The pattern of amputation drivers in PAD differs by history of DM, with infection being the dominant etiology in those with DM and ischemia in those without DM. Greater focus is needed on the prognostic importance of minor amputation and of the multifactorial etiologies of amputation in PAD. Nomenclature with anatomical description of amputations and eliminating terms "major" or "minor" would seem appropriate.

Improvement in walking impairment following surgical and endovascular revascularization: Insights from VOYAGER PAD.

BACKGROUND: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described. METHODS: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial. RESULTS: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks. CONCLUSION: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

High Rates of Recurrent Revascularization in Acute Limb Ischemia - A National Surgical Quality Improvement Program Study.

BACKGROUND: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to review outcomes of acute limb ischemia (ALI) patients following open surgical intervention for ALI. METHODS: A previously validated tool was used to identify ALI patients in NSQIP undergoing open surgical revascularization from 2012 to 2017. Multivariable analysis was performed for the primary outcome of reoperation and secondary outcome of readmission and infection. RESULTS: A total of 2,878 ALI patients underwent open revascularization; 35.7% were transfers from another acute care hospital. A total of 13.8% required reoperation and 7.9% required readmission within 30 days. A total of 32% of reoperations were recurrent revascularization, representing 4.4% of all ALI patients. A total of 58.7% of patients were female and either overweight or obese. Younger age (odds ratio OR 0.991 [0.984-0.999], P = 0.02), underweight patients (OR 1.159 [0.667-2.01], P = 0.05), pre-operative steroid use (OR 1.61 [1.07-2.41], P = 0.02), and perioperative transfusion (OR 2.02 [1.04-3.95], P = 0.04) predicted reoperations. CONCLUSIONS: This registry series demonstrates all-cause ALI patients are a different population than PAD with different risk factors. Despite being a time-critical condition, ALI has higher interhospital transfer rates than ACS or ruptured aneurysm. Following open revascularization, ALI outcomes are worse than ACS but better than ruptured AAA. These outcomes do not appear related to patient factors in contrast to revascularization for chronic PAD.

Cadaver Simulation is Associated with Increased Comfort in Performing Open Vascular Surgery Among Integrated Vascular Surgery (0+5) Residents and Recent Graduates.

BACKGROUND: With the evolution in vascular surgery toward increased endovascular therapy and decreased open surgical training, comfort with open procedures by current trainees is declining. A proposed method to improve this discomfort is simulator training. We hypothesized that open, cadaver, and endovascular surgery simulation would be associated with increased self-perceived comfort in performing corresponding procedures. METHODS: Integrated (0 + 5) vascular surgery residents and recent graduates in the United States were asked to complete a survey quantifying comfort via a Likert scale with procedures and experience with simulation training. Simulation groups were then matched using coarsened exact matching. Ordinal logistic regression assessed the association between simulation experience and comfort in performing procedures. RESULTS: Surveys were completed by 68 trainees and 20 attending surgeons in their first 5 years of practice. On unmatched analyses, there were no significant differences in comfort in performing any open or endovascular aorto-mesenteric or peripheral vascular procedures between respondents who reported experience with open or endovascular simulation, respectively. However, respondents who reported cadaver simulation experience (58%, 51/88) had a significantly higher reported comfort score performing open juxtarenal aortic repair (2.4 vs. 1.7), superior mesenteric artery thrombectomy or bypass (2.5 vs. 1.9), inferior vena cava or iliac vein repair (2.2 vs. 1.7), axillary-femoral artery bypass (3.4 vs. 2.5), femoral-popliteal artery bypass (3.7 vs. 2.8), and inframalleolar artery bypass (2.8 vs. 2.1; all P < 0.05). After matching on training level, number of abdominal cases completed, and number of open vascular cases completed, ordinal logistic regression demonstrated that previous cadaver simulation was significantly associated with increased comfort in performing open aortic repairs, venous repair, visceral revascularization, and peripheral bypasses. CONCLUSIONS: In this nationally representative sample, cadaver, but not open or endovascular, simulation was associated with increased comfort in performing open vascular surgery. Providing cadaver simulation to trainees may help to improve comfort levels in performing open surgery. Integrated vascular surgery training programs should consider implementing these experiences into their curriculum.

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial.

AIMS: In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. METHODS AND RESULTS: The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). CONCLUSION: Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety.

BACKGROUND: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. METHODS: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization. RESULTS: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71-1.01) with clopidogrel and 0.86 (95% CI, 0.73-1.01) without clopidogrel without statistical heterogeneity (P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14-1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22-1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44-7.13]) compared with shorter durations of clopidogrel (P for trend=0.06). CONCLUSIONS: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.

Popliteal scoring assessment for vascular extremity injuries in trauma study.

OBJECTIVE: Traumatic popliteal vascular injuries are associated with the highest risk of limb loss of all peripheral vascular injuries. A method to evaluate the predictors of amputation is needed because previous scores could not be validated. In the present study, we aimed to provide a simplified scoring system (POPSAVEIT [popliteal scoring assessment for vascular extremity injuries in trauma]) that could be used preoperatively to risk stratify patients with traumatic popliteal vascular injuries for amputation. METHODS: A review of patients sustaining traumatic popliteal artery injuries was performed. Patients requiring amputation were compared with those with limb salvage at the last follow-up. Of these patients, 80% were randomly assigned to a training group for score generation and 20% to a testing group for validation. Significant predictors of amputation (P < .1) on univariate analysis were included in a multivariable analysis. Those with P < .05 on multivariable analysis were assigned points according to the relative value of their odds ratios (ORs). Receiver operating characteristic curves were generated to determine low- vs high-risk scores. An area under the curve of >0.65 was considered adequate for validation. RESULTS: A total of 355 patients were included, with an overall amputation rate of 16%. On multivariate regression analysis, the risk factors independently associated with amputation in the final model were as follows: systolic blood pressure <90 mm Hg (OR, 3.2; P = .027; 1 point), associated orthopedic injury (OR, 4.9; P = .014; 2 points), and a lack of preoperative pedal Doppler signals (OR, 5.5; P = .002; 2 points [or 1 point for a lack of palpable pedal pulses if Doppler signal data were unavailable]). A score of ≥3 was found to maximize the sensitivity (85%) and specificity (49%) for a high risk of amputation. The receiver operating characteristic curve for the validation group had an area under the curve of 0.750, meeting the threshold for score validation. CONCLUSIONS: The POPSAVEIT score provides a simple and practical method to effectively stratify patients preoperatively into low- and high-risk major amputation categories.

Contemporary outcomes of traumatic popliteal artery injury repair from the popliteal scoring assessment for vascular extremity injury in trauma study.

OBJECTIVE: Traumatic popliteal artery injuries are associated with the greatest risk of limb loss of all peripheral vascular injuries, with amputation rates of 10% to 15%. The purpose of the present study was to examine the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries and identify the factors independently associated with limb loss. METHODS: A multi-institutional retrospective review of all patients with traumatic popliteal artery injuries from 2007 to 2018 was performed. All the patients who had undergone operative repair of popliteal arterial injuries were included in the present analysis. The patients who had required a major lower extremity amputation (transtibial or transfemoral) were compared with those with successful limb salvage at the last follow-up. The significant predictors (P < .05) for amputation on univariate analysis were included in a multivariable analysis. RESULTS: A total of 302 patients from 11 institutions were included in the present analysis. The median age was 32 years (interquartile range, 21-40 years), and 79% were men. The median follow-up was 72 days (interquartile range, 20-366 days). The overall major amputation rate was 13%. Primary repair had been performed in 17% of patients, patch repair in 2%, and interposition or bypass in 81%. One patient had undergone endovascular repair with stenting. The overall 1-year primary patency was 89%. Of the patients who had lost primary patency, 46% ultimately required major amputation. Early loss (within 30 days postoperatively) of primary patency was five times more frequent for the patients who had subsequently required amputation. On multivariate regression, the significant perioperative factors independently associated with major amputation included the initial POPSAVEIT (popliteal scoring assessment for vascular extremity injury in trauma) score, loss of primary patency, absence of detectable immediate postoperative pedal Doppler signals, and lack of postoperative antiplatelet therapy. Concomitant popliteal vein injury, popliteal injury location (P1, P2, P3), injury severity score, and tibial vs popliteal distal bypass target were not independently associated with amputation. CONCLUSIONS: Traumatic popliteal artery injuries are associated with a significant rate of major amputation. The preoperative POPSAVEIT score remained independently associated with amputation after including the perioperative factors. The lack of postoperative pedal Doppler signals and loss of primary patency were highly associated with major amputation. The use of postoperative antiplatelet therapy was inversely associated with amputation, perhaps indicating a protective effect.

Self-Perceived Comfort Performing Vascular Surgery Procedures among Senior Vascular Surgery Trainees and Recent Graduates.

OBJECTIVE: In the last two decades, vascular surgery training evolved from exclusively learning open skills to learning endovascular skills in addition to a functional reduction in training duration with 0+5 residency programs. The implications for this on trainee evolution to independence are unknown. We aimed to assess self-perceived comfort performing open and endovascular procedures and to identify predictors of high comfort among senior vascular surgery trainees and recent graduates. METHODS: Junior and senior 0+5 vascular surgery residents, traditional fellows, and attendings in their first 4 years of practice were asked to complete a survey assessing the number of vascular procedures performed to date, comfort performing these procedures on a Likert scale, and validated scales of self-efficacy and grit. Groups were then matched by training level and age. Logistic regression identified independent predictors of the top quartile of self-perceived comfort performing procedures. RESULTS: Surveys were completed by 92 trainees and 71 attending surgeons in their first 4 years of practice. After matching, completing ≥7 open juxtarenal aortic repairs (OR = 4.73, 95% CI = 1.59-14.07) and a higher self-efficacy score (OR = 3.24, 95% CI = 1.20-8.76), were independent predictors of top quartile comfort performing open vascular procedures. 0+5 residency training inversely correlated with top quartile comfort performing open vascular operations (OR = 0.12, 95% CI = 0.03-0.47). Completing ≥7 complex EVARs (OR = 3.94, 95% CI = 1.61-9.59) and a higher self-efficacy personality score (OR = 2.76, 95% CI = 1.09-7.02) were predictors of top quartile comfort performing endovascular procedures. CONCLUSION: In this nationally representative survey, both trainees and junior attendings completed a paucity of complex open vascular cases, which corresponded to reduced comfort performing these procedures. Furthermore, 0+5 residency training was associated with lower self-perceived comfort performing open vascular surgery, a trend that persisted through the first years of practice. Endovascular comfort did not show a similar correlation.

Tackling Elevated Risk in PAD: Focus on Antithrombotic and Lipid Therapy for PAD.

The PAD population is at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Risk factor modification, symptom control, antithrombotic, and lipid therapies are the mainstays of PAD medical therapy. Recent data has challenged prior recommendations regarding the optimal secondary prevention strategies in PAD. PURPOSE OF REVIEW: To review clinical evidence from large randomized controlled trials showing the benefit of antithrombotic and lipid therapy in the PAD population. RECENT FINDINGS: The COMPASS trial challenged prior recommendations regarding anticoagulation in PAD. Among the PAD subgroup, rivaroxaban 2.5 mg plus aspirin reduced MACE (HR 0.72, 95% CI 0.57-0.90, p = 0.0047), MALE (HR 0.54, 95% CI 0.35-0.82, p = 0.0037), and major amputation (HR 0.30, 95% CI 0.11-0.80, p = 0.011) compared with aspirin monotherapy. The THEMIS trial showed a 55% risk reduction for MALE with ticagrelor DAPT compared with aspirin monotherapy (HR 0.45, 95% CI 0.23-0.86). The FOURIER trial revealed that lowering LDL cholesterol below current targets with a PCSK9 inhibitor reduced MACE (HR 0.73, 95% CI 0.59-0.91, p = 0.0040) and MALE (HR 0.43, 95% CI 0.19-0.99, p = 0.042) in subjects with symptomatic PAD. Recent high-quality evidence shows the benefit of antiplatelet therapy, anticoagulation therapy, and lipid therapy in reducing MACE and MALE in PAD. Despite these findings, implementation remains a challenge and focus should now shift towards adopting evidence-based recommendations in clinical practice.

Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease.

BACKGROUND: The treatment of peripheral artery disease with percutaneous transluminal angioplasty is limited by the occurrence of vessel recoil and restenosis. Drug-coated angioplasty balloons deliver antiproliferative agents directly to the artery, potentially improving vessel patency by reducing restenosis. METHODS: In this single-blind, randomized trial conducted at 54 sites, we assigned, in a 2:1 ratio, 476 patients with symptomatic intermittent claudication or ischemic pain while at rest and angiographically significant atherosclerotic lesions to angioplasty with a paclitaxel-coated balloon or to standard angioplasty. The primary efficacy end point was primary patency of the target lesion at 12 months (defined as freedom from binary restenosis or from the need for target-lesion revascularization). The primary safety end point was a composite of freedom from perioperative death from any cause and freedom at 12 months from limb-related death (i.e., death from a medical complication related to a limb), amputation, and reintervention. RESULTS: The two groups were well matched at baseline; 42.9% of the patients had diabetes, and 34.7% were current smokers. At 12 months, the rate of primary patency among patients who had undergone angioplasty with the drug-coated balloon was superior to that among patients who had undergone conventional angioplasty (65.2% vs. 52.6%, P=0.02). The proportion of patients free from primary safety events was 83.9% with the drug-coated balloon and 79.0% with standard angioplasty (P=0.005 for noninferiority). There were no significant between-group differences in functional outcomes or in the rates of death, amputation, thrombosis, or reintervention. CONCLUSIONS: Among patients with symptomatic femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon resulted in a rate of primary patency at 12 months that was higher than the rate with angioplasty with a standard balloon. The drug-coated balloon was noninferior to the standard balloon with respect to safety. (Funded by Lutonix-Bard; LEVANT 2 ClinicalTrials.gov number, NCT01412541.).

Rationale and design for the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD).

BACKGROUND: Patients with peripheral artery disease (PAD) undergoing a lower-extremity revascularization are at heightened risk for ischemic cardiac and limb events. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in coronary disease populations, this approach has not been well studied or shown consistent benefit in PAD. Recent trial evidence demonstrated that a treatment strategy of rivaroxaban added to background antiplatelet therapy reduced ischemic risk in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease. Whether these benefits extend to the population of patients with symptomatic lower-extremity PAD undergoing revascularization is the objective of the VOYAGER PAD trial. STUDY DESIGN: VOYAGER PAD is an international randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of rivaroxaban in symptomatic PAD patients undergoing a peripheral surgical and/or endovascular revascularization. Patients are randomized in a 1:1 ratio to either rivaroxaban 2.5 mg twice daily or placebo, on a background of low-dose aspirin (100 mg daily). In addition, the use of a limited course of P2Y12 inhibition is allowed at the discretion of the site investigator. The primary efficacy end point is a novel composite of myocardial infarction, ischemic stroke, cardiovascular death, acute limb ischemia, and major amputation of vascular etiology. The primary safety end point is major bleeding according to the Thrombolysis in Myocardial Infarction definition. Enrolment began in August 2015 and will complete randomization of at least 6,500 patients by January 2018. This event-driven trial is expected to observe outcomes over a mean patient follow-up of 30 months. CONCLUSIONS: VOYAGER PAD is evaluating the efficacy of rivaroxaban added to background antiplatelet therapy to reduce major cardiovascular and limb ischemic vascular outcomes in the high-risk population of PAD patients undergoing peripheral revascularization.

Morbidity of endovascular abdominal aortic aneurysm repair is directly related to diameter.

OBJECTIVE: Previous randomized controlled trials have defined specific size thresholds to guide surgical decision-making in patients presenting with an abdominal aortic aneurysm (AAA). With recent advances in endovascular techniques, the anatomic considerations of AAA repair are rapidly changing. Our specific aims were to evaluate the most recent national population data to compare anatomic differences and perioperative outcomes in patients with AAA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried from 2011 to 2015 using the targeted vascular public use file. Patients with AAA undergoing elective open or endovascular repair were included. Risk factors and outcomes were stratified by size and divided into quartiles for categorical comparison. A logistic regression model was used to compare the impact of size on morbidity and mortality with each technique. A risk adjustment model used all preoperative criteria to generate observed and expected values for open and endovascular repair. RESULTS: There were 10,026 patients who underwent elective AAA repair, 8182 (81.6%) endovascular and 1844 (18.4%) open. Repairs were divided into density quartiles for a logistic analysis: smallest quartile, 3.5 to 5 cm; second quartile, 5.01 to 5.5 cm; third quartile, 5.51 to 6.2 cm; and largest quartile, >6.2 cm. Patients with larger aneurysms (>6.2 cm) were more likely to be male, to have a dependent functional status, and to have increased blood urea nitrogen concentration and American Society of Anesthesiologists score (P < .05). Larger aneurysms had longer operative time (162 vs 135 minutes) and greater extension toward the renal and iliac vessels (all P < .05). Risk adjustment revealed an observed/expected morbidity plot that favored endovascular repair throughout the size range but confirmed lack of size effect within the open repair category. The adjusted increase in morbidity with endovascular repair is 9.7% per centimeter increase in size of AAA. These trends remained true with an infrarenal subgroup analysis. CONCLUSIONS: Patients with a larger AAA have comorbidities and anatomic factors associated with a more difficult repair. The higher morbidity seen with larger aneurysms represents both anatomic and patient factors but seems to have a greater impact on endovascular repairs. However, endovascular repair still results in fewer near-term complications than open repair across all size strata.