Rivaroxaban for Patients with Intermittent Claudication.

BACKGROUND: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease. METHODS: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding. RESULTS: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group. CONCLUSIONS: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).

Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Cost-effectiveness analysis of extended thromboprophylaxis with rivaroxaban versus no prophylaxis in high-risk patients after hospitalisation for COVID-19: an economic modelling study.

Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy. Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis. Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY. Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option. Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil.

Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial : Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial).

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

Stent fractures in the superficial femoral artery: predisposing factors and their implications.

Background: Fractures in stents implanted in the superficial femoral artery (SFA) are recognized complications of endovascular management of this arterial territory. Objectives: The objective of this study was to determine the prevalence of fractures in stents implanted in the SFA and to identify predisposing factors for these fractures together with their impact on the patency of these devices. Methods: The study included 39 patients (65.7±9.0 years) who previously underwent angioplasty for delivery of 56 stents into the SFA. During follow-up, which ranged from 7 to 46 months, variables were collected on the characteristics of the lesions treated and characteristics of the stents implanted. Two examiners independently analyzed digital radiographs for the presence of stent fractures and the patency of the devices. Results: We found a 10.7% prevalence of fracture of implanted stents. Implantation of multiple stents was identified as a significant predisposing factor for fractures. We observed a marked tendency for fractures in female patients and in lesions treated with longer stents (> 150 mm). Stenosis exceeding 50% and occlusions were significantly more frequent in fractured stents. Conclusions: This study suggests that implants longer than 150 mm and multiple stents are associated with higher device fracture rates. In cases with stent fractures, stenoses exceeding 50% and occlusions were significantly more frequent.

Contexto: As fraturas de stents implantados na artéria femoral superficial (AFS) são uma complicação reconhecida pós-tratamento endovascular desse território arterial. Objetivos: Este estudo objetivou determinar a presença de fraturas nos stents implantados na AFS e identificar fatores predisponentes para essas fraturas, juntamente com o impacto na perviedade desses dispositivos. Métodos: Foram incluídos 39 pacientes (65,7±9,0 anos) previamente submetidos à angioplastia para colocação de 56 stents na AFS. Durante o seguimento, que variou de 7 a 46 meses, foram coletadas variáveis referentes às características das lesões tratadas e às características dos stents implantados. Dois examinadores analisaram radiografias digitais para verificar a presença de fraturas de stent e a perviedade dos dispositivos independentemente. Resultados: Foi encontrada uma prevalência de 10,7% de fratura nos stents implantados. O implante de múltiplos stents foi identificado como fator predisponente significativo para fraturas. Foi observada uma tendência acentuada de fraturas em pacientes do sexo feminino e em lesões tratadas com stents mais longos (> 150 mm). As estenoses acima de 50% e as oclusões foram significativamente mais frequentes em stents fraturados. Conclusões: Este estudo sugere que implantes de múltiplos stents ou de stents com extensão maior que 150 mm estão associados a maiores taxas de fraturas do dispositivo. No caso de fraturas de stents, as estenoses mais significativas que 50% e as oclusões foram consideravelmente mais frequentes.

Rivaroxaban with Aspirin Versus Aspirin for Peripheral Arterial Disease and Intermittent Claudication. Rationale and Design of the COMPASS CLAUDICATION Trial.

BACKGROUND: The COMPASS trial demonstrated that in patients with peripheral arterial disease, the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on claudication distance. STUDY DESIGN: Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from the baseline to 24 weeks, measured by 6 min walking test and treadmill test. The primary safety outcome is the incidence of major bleeding and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria. SUMMARY: The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.

Can we replace computed tomography angiography by contrast-enhanced ultrasound in the surveillance of patients submitted to aortoiliac aneurysm repair?

OBJECTIVES: This study was designed for evaluation of CEUS (contrast-enhanced ultrasound) for the detection of endoleaks after EVAR (endovascular aortic aneurysms repair) as an alternative to CTA (computed tomography angiography), the gold standard in post-EVAR surveillance. METHODS: Post-EVAR surveillance of patients who underwent CEUS and CTA was retrospectively analyzed to compare the accuracy of CEUS compared to CTA. For that, the following parameters were analyzed: the largest aneurysm diameter, type of endoleaks, and the time elapsed after EVAR using both surveillance tests. RESULTS: The study involved 110 pairs of exams in patients with infrarenal aortoiliac or isolated iliac artery aneurysm, covering predominantly a male population (89%). The time elapsed after EVAR using CEUS or CTA exams were statistically similar, ranging from one to 58 months (mean 12.2) and one to 65 months (mean 9.7), respectively (p = 0.124). CEUS sensitivity was 75.5%, specificity 96.7%, false positives were 24.5%, and false negatives were 3.3%. The accuracy between the two exams was 87.3%. A secondary analysis, comparing CTA with CEUS as a reference standard, revealed CEUS sensitivity of 24.5%, higher than CTA for detecting endoleaks, with a concordance rate of true positive results of 75.5%. Among the endoleaks detected solely by CEUS (12 cases), one case was type Ia and eleven were type II, while those detected only by CTA (2 cases), one was type Ia and one type II. Additionally, a type II endoleak associated with type Ib, identified by CEUS, was seen as type II for CTA only. There was no difference between the pre-EVAR and the post-EVAR diameters of aortoiliac aneurysm (p = 0.058), both for CEUS and CTA. Computed tomography angiography, on the other hand, showed significant aneurysm diameter reduction compared to CEUS for isolated iliac artery aneurysms (p < 0.001). CONCLUSION: Contrast-enhanced ultrasound was more effective than CTA in identifying and characterizing endoleaks in patients undergoing EVAR, especially type II endoleaks. The advantages include efficacy and, particularly, safety, and must be considered in EVAR surveillance protocols so that its use becomes widespread. We understand that CEUS, as a surveillance exam, considerably reduces risks to patients compared to CTA.

Stent fractures in the superficial femoral artery: predisposing factors and their implications / Fraturas de stents na artéria femoral superficial: fatores predisponentes e suas implicações

Abstract Background Fractures in stents implanted in the superficial femoral artery (SFA) are recognized complications of endovascular management of this arterial territory. Objectives The objective of this study was to determine the prevalence of fractures in stents implanted in the SFA and to identify predisposing factors for these fractures together with their impact on the patency of these devices. Methods The study included 39 patients (65.7±9.0 years) who previously underwent angioplasty for delivery of 56 stents into the SFA. During follow-up, which ranged from 7 to 46 months, variables were collected on the characteristics of the lesions treated and characteristics of the stents implanted. Two examiners independently analyzed digital radiographs for the presence of stent fractures and the patency of the devices. Results We found a 10.7% prevalence of fracture of implanted stents. Implantation of multiple stents was identified as a significant predisposing factor for fractures. We observed a marked tendency for fractures in female patients and in lesions treated with longer stents (> 150 mm). Stenosis exceeding 50% and occlusions were significantly more frequent in fractured stents. Conclusions This study suggests that implants longer than 150 mm and multiple stents are associated with higher device fracture rates. In cases with stent fractures, stenoses exceeding 50% and occlusions were significantly more frequent.

Resumo Contexto As fraturas de stents implantados na artéria femoral superficial (AFS) são uma complicação reconhecida pós-tratamento endovascular desse território arterial. Objetivos Este estudo objetivou determinar a presença de fraturas nos stents implantados na AFS e identificar fatores predisponentes para essas fraturas, juntamente com o impacto na perviedade desses dispositivos. Métodos Foram incluídos 39 pacientes (65,7±9,0 anos) previamente submetidos à angioplastia para colocação de 56 stents na AFS. Durante o seguimento, que variou de 7 a 46 meses, foram coletadas variáveis referentes às características das lesões tratadas e às características dos stents implantados. Dois examinadores analisaram radiografias digitais para verificar a presença de fraturas de stent e a perviedade dos dispositivos independentemente. Resultados Foi encontrada uma prevalência de 10,7% de fratura nos stents implantados. O implante de múltiplos stents foi identificado como fator predisponente significativo para fraturas. Foi observada uma tendência acentuada de fraturas em pacientes do sexo feminino e em lesões tratadas com stents mais longos (> 150 mm). As estenoses acima de 50% e as oclusões foram significativamente mais frequentes em stents fraturados. Conclusões Este estudo sugere que implantes de múltiplos stents ou de stents com extensão maior que 150 mm estão associados a maiores taxas de fraturas do dispositivo. No caso de fraturas de stents, as estenoses mais significativas que 50% e as oclusões foram consideravelmente mais frequentes.

Anxiety and depression scores in patients subjected to aortic and iliac aneurysm repair procedures.

OBJECTIVE: This study examines the changes in anxiety and depression scores of 84 patients subjected to aortic or iliac aneurysm correction with no previous psychiatric history. METHODS: Patients were referred to the evaluation using the Beck Anxiety and Depression Inventories no more than 3 days before surgery (i.e., preoperative [Pre-Op]), 30 days after revascularization (i.e., Early postoperative [PO]), and at least 6 months after revascularization (i.e., Late PO). RESULTS: Mean anxiety scores declined from baseline at both the Early (mean difference: 2.75, p<0.001) and Late PO (mean difference: 2.74, p=0.001). The depression levels showed no significant variation in either evaluation (Early PO; mean difference: -0.84, p>0.05, Late PO: 0.87, p=0.05). A more severe degree of anxiety at baseline was related to better anxiety results both in the Early PO (p=0.041) and Late PO (p=0.008). An endovascular technique was related to the improvement in depression symptoms in the Early PO (p=0.01) but the worsening of the symptoms in the Late PO (p=0.033). CONCLUSIONS: Patients subjected to aortoiliac aneurysm corrections have a higher incidence of anxiety and depressive symptoms. Anxiety symptoms, but not the depressive ones, improved considerably following the successful treatment. The formal psychiatric evaluation may be beneficial for patients with less improvement in the symptom.

Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Anxiety and Depression Scores in Patients Subjected to Arterial Revascularization for Critical Limb Ischemia.

OBJECTIVES: This study aims to examine the changes in anxiety and depression scores in 138 patients with critical limb ischemia (rest pain or gangrene) who had no previous psychiatric history, at 30 days and 6 months after surgical revascularization. METHODS: Patients were submitted to a questionnaire-based evaluation using the Beck Anxiety and Depression Inventories before surgery (no more than three days before surgery) ("Pre-Op"), 30 days after surgical revascularization ("Early PO") and at least 6 months after surgical revascularization ("Late PO"). The cut-off scores for depression were (1) < 10, no depression or minimal depression; (2) 10‒18, mild to moderate depression; (3) 19‒29, moderate to severe depression; and (4) 30‒63, severe depression. The cut-off scores for anxiety were (1) < 8, no anxiety or minimal anxiety; (2) 8‒15, mild anxiety; (3) 16‒25, moderate anxiety; and (4) 26‒63, severe anxiety. RESULTS: No perioperative mortality was observed 30 days after surgical revascularization. Thirty-nine (28.2%) patients underwent major (above-ankle) amputation within 30 days. Mean anxiety and depression scores, respectively, declined from 12.48 ± 9.74 (mean ± SD) and 16.92 ± 12.48 preoperatively to 4.89 ± 7.04 and 6.52 ± 9.36 postoperatively (P<0.001, both). Anxiety and depression scores were not significantly affected by preoperative comorbidities (systemic arterial hypertension, diabetes mellitus, previous stroke, and smoking), affected arterial territory (aortoiliac, femoropopliteal, or infrapopliteal), or surgical technique (open surgery vs endovascular therapy). Only patients undergoing amputation within 30 days showed no improvement in depressive symptoms. CONCLUSIONS: Patients with critical limb ischemia have a high incidence of anxiety and depressive symptoms, which improve considerably after successful surgical revascularization. Major amputation was associated with a lack of improvement in depression scores. A formal psychiatric evaluation may be beneficial in patients who show no improvement in depressive symptoms.

Arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg: qual a diferença? / Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular.

Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version.

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020.

This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Rationale and design for the study Apixaban versus ClopidoGRel on a background of aspirin in patient undergoing InfraPoPliteal angioplasty for critical limb ischemia: AGRIPPA trial.

BACKGROUND: New antithrombotic strategies that reduce primary thrombosis and restenosis might improve vascular outcomes in patients with peripheral artery disease (PAD) undergoing arterial angioplasty. The study objective is to evaluate the potential benefit of apixaban plus aspirin compared with standard of care dual antiplatelet therapy (DAPT) in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization. STUDY DESIGN: This multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, proof-of-concept, exploratory trial aims to randomize 200 patients 72 hours after successful infrapopliteal angioplasty for critical limb ischemia (CLI). Patients will be randomly assigned in a 1:1 ratio to receive oral apixaban (2.5 mg twice daily) plus aspirin (100 mg once daily) for 12 months or clopidogrel (75 mg daily) for at least 3 months on a background of aspirin (100 mg once daily) for 12 months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation, or restenosis/occlusion (RAS) in addition to major adverse cardiovascular events - MACE (myocardial infarction, stroke or cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding or clinically relevant non-major bleeding at 12 months. SUMMARY: This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared with DAPT (clopidogrel plus aspirin) in patients with CLI undergoing endovascular infrapopliteal revascularization and might prove the concept of an alternative antithrombotic regimen for these patients to be tested in a future large randomized clinical trial.

Direct Oral Anticoagulants and Cancer-Associated Thrombosis Management. Where Do We Stand in 2019?

Direct oral anticoagulants (DOACs) are now widely used for the management of venous thromboembolism (VTE) that now includes cancer-associated thrombosis. This review summarizes recent data on VTE prophylaxis and treatment, new challenges, guidelines, and updates as well as the current place for DOACs on the emerging cancer-associated VTE management landscape.

Comparison of 15-20 mmHg versus 20-30 mmHg Compression Stockings in Reducing Occupational Oedema in Standing and Seated Healthy Individuals.

BACKGROUND: Elastic compression stockings (ECS) are effective in preventing and reducing occupational edema (OE), but the optimal pressure according to the prevalent working position during the day is still controversial. OBJECTIVE: To compare the effectiveness of ECS with different pressures (15-20 mmHg or 20-30 mmHg) for reducing OE in individuals working in different prolonged postures. METHODS: This cross-sectional study comprised 116 lower limbs of 58 individuals divided into three groups according to their prevalent postures over the day (sitting, standing, or combination). Volumetric measurements were taken at the beginning and at the end of three consecutive days. On the first day, individuals did not use compression stockings; on the second and third days, they used, respectively, 15-20 mmHg and 20-30 mmHg knee-length stockings. Differences between morning and evening volumes (measured edema) were calculated, compared, and correlated. RESULTS: Volumetric variations were significantly lower on the second compared to the first day when individuals in all three groups used 15-20 mmHg compression stockings (p-value < 0.001). Measurements were even lower when they used 20-30 mmHg stockings: this decrease was more significant for the sitting (p-value < 0.001) than the standing (p-value < 0.05) and combined groups (p-value < 0.05). Reduction of measured edema was more significant in individuals working in a prolonged seated position. No significant difference was found only on comparing sitting and standing groups after the use of the 15-20 mmHg compression stockings. CONCLUSIONS: The use of ECS over a working day reduces OE in prolonged sitting, standing, and combined positions, with the reductions being greater with the higher pressure.

Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial.

Several biosimilar versions of enoxaparin are already approved and in use globally. Analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in clinical outcomes between biosimilar and branded enoxaparin. This study evaluated the efficacy and safety of biosimilar Cristália versus branded Sanofi enoxaparin in venous thromboembolism (VTE) prevention in patients undergoing major abdominal surgery at risk for VTE. In this randomized, prospective single-blind study, we compared Cristália enoxaparin (Ce), a biosimilar version, versus branded Sanofi enoxaparin (Se; at a dose of 40 mg subcutaneously per day postoperatively from 7 to 10 days) in 243 patients submitted to major abdominal surgery at risk for VTE for VTE prevention. The primary efficacy outcome was occurrence of VTE or death related to VTE. The principal safety outcomes were a combination of major bleeding and clinically relevant non-major bleeding. Bilateral duplex scanning of the legs was performed from days 10 to 14, and follow-ups were performed up to 60 days after surgery. The incidence of VTE was 4.9% in the Cristália group and 1.1% in the Sanofi group (absolute risk difference = 3.80%, 95% confidence interval [CI]: -1.4%-9.0%) yielding noninferiority since the 95% CI does not reach the prespecified value Δ = 20%. Clinically significant bleeding occurred in 9.9% in the Cristália group and in 5.5% in the Sanofi group (n.s. ). In conclusion, this study suggests that 40 mg once daily of Ce, a biosimilar enoxaparin, is as effective and safe as the branded Sanofi enoxaparin in the prophylaxis of VTE in patients submitted to major abdominal surgery at risk for VTE.

Rupture of Thrombosed Popliteal Aneurysm: A Case Report.

Asymptomatic rupture of a popliteal arterial aneurysm (AAP) is rare but has been previously reported in the literature. Here, we present the first case of a thrombosed AAP that ruptured and developed into an abscess. We present the case of an 83-year-old male patient who was admitted to the emergency room in an impaired general condition, with a 3-month history of a daily fever that mainly occurred in the evening (38°C), a lack of appetite, and weight loss of 18 kg over 3 months. On initial physical examination in the emergency room, the patient presented with fever (37.8°C), a heart rate of 105 bpm, a blood pressure of 110/70 mm Hg, and bulging in the posterior aspect of the right thigh that was hard, painless, without hyperemia, and without localized heat on palpation. The femoral pulses were normal bilaterally, but the popliteal and distal pulses in the right lower limb were absent. A magnetic resonance imaging demonstrated thrombosis of the right AAP associated with continuity contour loss and images compatible with collection with low degree on T1 and intermediate signal intensity on T2, which may correspond to the subacute bleeding areas that measured 10.6 × 5.9 × 4.0 cm and that were located between the muscle belly of the sartorius, semimembranosus, and vastus muscles inferiorly. There was another collection (with similar characteristics) that measured 5.4 × 4.2 × 2.4 cm and that was located medially from the biceps femoral muscle. The patient consented to the resection of the aneurysm and the ligation of the collateral arteries. First, we dissected down to the femoral artery proximal to the aneurysm and the popliteal artery at the P2 segment where there was no evidence of infection or rupture. The surgical wound was washed with 10 L of 0.9% saline solution, samples were sent to pathology for culture, and the surgical wound was drained with a closed drain. We decided not to revascularize the limb because there was good perfusion and a current infection.

Mycotic aneurysm with aortoduodenal fistula.

Firstly described in the 19th century by Sir William Osler, the mycotic aneurysm (MA) is a rare entity characterized by an abnormal arterial dilation, which is potentially fatal, and is associated with the infection of the vascular wall. Elderly patients are mostly involved, especially when risk factors like chronic diseases, immunosuppression, neoplasia, and arterial manipulation are associated. The authors report the case of a young male patient diagnosed with an aortic aneurysm of infectious origin in the presence of repeated negative blood cultures. The diagnostic hypothesis was raised when the patient was hospitalized for an inguinal hernia surgery. The diagnosis was confirmed based on imaging findings consistent with mycotic aneurism. The patient was treated with an endovascular prosthesis associated with a long-lasting antibiotic therapy. Five months later, the patient attended the emergency unit presenting an upper digestive hemorrhage and shock, from which he died. The autopsy revealed a huge aneurysm of the abdominal aorta with an aortoduodenal fistula. The histological examination of the arterial wall revealed a marked inflammatory process, extensive destruction of the arterial wall, and the presence of Gram-positive bacteria. This case highlights the atypical presentation of a MA associated with an aortoduodenal fistula. Besides the early age of the patient, no primary arterial disease could be found, and no source of infection was detected.