Generic versus branded enoxaparin in prophylaxis and treatment of vein thrombosis / Enoxaparina genérica versus padrão-ouro na terapia e profilaxia de trombose venosa

Objectives: to compare the biological efficacy of generic enoxaparin (HeptronTM) versus branded Sanofi-Aventis enoxaparin for prophylaxis and treatment of lower-extremity deep venous thrombosis (DVT) in a prospective, randomized, open-label study. Methods: patients with diagnosed lower-extremity DVT (therapeutic branch, n=57) and patients requiring venous thromboembolism (VTE) prophylaxis after arterial vascular surgery or major lower-extremity amputations (prophylactic branch, n=57) were randomized to receive generic or branded enoxaparin for up to seven days. Enoxaparin activity was measured by estimating blood anti-factor Xa levels at the peak plasma concentration. As secondary outcomes, development or progression of VTE events, major adverse events and major bleeding events were considered for efficacy and safety comparisons. Results: DVT therapy: twenty-five patients received generic enoxaparin while 32 received branded enoxaparin (subcutaneous, 1 mg/kg BID). Mean percentages of anti-factor Xa levels within the target ranges were 62 ± 35.4% and 67.5 ± 24.7%, respectively (p= .035 for non-inferiority). No patient presented DVT progression, clinically detectable pulmonary embolism, or major bleeding events in any subgroup. DVT prophylaxis: Thirty patients received generic enoxaparin and 27 received branded enoxaparin (subcutaneous, 40 mg/day). Mean percentages of anti-factor Xa levels within the target ranges were 77.9 ± 30.9% and 77.8 ± 32.9%, respectively (p = .009 for non-inferiority). There were no cases of VTE or major bleeding events in any subgroup. Conclusion: generic and branded enoxaparins exhibited similar in vivo responses as measured by the anti-factor Xa activity, as well as similar clinical efficacy and safety outcomes. .

Objetivos: comparar a eficácia biológica da enoxaparina genérica (HeptronTM) versus enoxaparina Sanofi-Aventis na profilaxia e no tratamento da trombose venosa profunda (TVP) de membros inferiores em ensaio prospectivo, randomizado e não cego. Método: pacientes com diagnóstico de TVP de membros inferiores (grupo terapêutico, n = 57) e pacientes com indicação de profilaxia de tromboembolismo venoso (TEV), após cirurgias vasculares de grande porte ou amputações maiores (grupo profilático, n = 57), foram randomizados para receber a enoxaparina sob teste (HeptronTM) ou a droga padrão-ouro (Sanofi-Aventis). A atividade da enoxaparina foi mensurada pela análise diária da atividade antifator-Xa no pico de concentração plasmática das drogas. Foram coletados dados de ocorrência ou progressão de TVP/TEV, eventos adversos graves e sangramentos graves; e foram utilizados para a análise de eficácia e segurança clínica como objetivos secundários. Resultados: grupo terapêutico: 25 pacientes receberam enoxaparina genérica, e 32, a droga padrão-ouro (via subcutânea, 1 mg/kg, a cada 12 horas). Os percentuais médios de atividade antifator-Xa dentro dos limites terapêuticos foram de 62 ± 35,4% e 67,5 ± 24,7%, respectivamente (p = 0,035, para não inferioridade). Nenhum paciente apresentou progressão da TVP, embolia pulmonar clinicamente detectável ou sangramentos maiores. Grupo profilático: trinta pacientes receberam enoxaparina genérica, e 27, a droga padrão-ouro (via subcutânea, 40 mg/dia). Os percentuais médios de atividade antifator-Xa dentro dos limites terapêuticos foram de 77,9 ± 30.9% e 77,8 ± 32,9%, respectivamente (p = 0,009, para não inferioridade). Nenhum paciente desenvolveu TVP ou apresentou sangramentos maiores. Conclusão: enoxaparinas genéricas e de marca apresentaram respostas semelhantes em estudos in vivo, quando medidas pela atividade do anti-fator Xa, assim como eficácia clínica e dados de segurança similares. .

Endovascular treatment of peripheral arterial injury with covered stents: an experimental study in pigs

OBJECTIVE: To evaluate the feasibility of using endovascular repair to treat penetrating arterial injuries with covered stents. Feasibility was examined according to the circumferential extent of the injury. INTRODUCTION: Surgical trauma often increases the risk of major morbidity and mortality associated with vascular injury, and endovascular repair has many advantages in such situations. METHODS: Twenty white male domestic pigs weighing 28-38 kg with controlled vascular injuries were divided into four equal groups according to the circumferential extent of their vascular lesion (i.e., no lesion, lesion <50 percent, lesion >50 percent, and complete lesion). The left common carotid artery was dissected with proximal and distal control, and this procedure was followed by controlled sectioning of the arterial wall. Local manual compression was applied for 10 min and was followed by endovascular repair with the placement of a 5x50 mm VIABHAN TM covered stent using the femoral approach. We also monitored additional variables, such as the duration of the procedures (the mean was 56.3 ± 19.1 min), ultrasound parameters (e.g., maximum arterial diameter, peak systolic and diastolic velocity, and resistance index), arteriography findings, and fluctuations in vital signs (e.g., cardiac output, arterial pressure, and central venous pressure). RESULTS: The experimental procedure was found to be feasible and reproducible. Repairs were successful in all animals in the control (no lesion) and <50 percent lesion groups. Success was also achieved in four out of five pigs in the >50 percent group and in one pig in the complete lesion group. DISCUSSION: The endovascular repair of an arterial injury is possible, but success depends on the circumferential extent of the arterial lesion. The present experimental model, which involved endovascular techniques, highlighted important factors that must be considered in future studies involving similar animals and materials.

Comparison of common carotid artery intima-media thickness between Brazilian Euro-descendants and Afro-descendants with atherosclerosis risk factors

OBJECTIVE: To compare common carotid intima-media thickness (IMT) between the two major Brazilian ethnic groups (those of African descent and those of European descent) among individuals with one or more risk factors for atherosclerotic disease. METHOD: Two hundred and six patients with one or more risk factors for atherosclerotic disease were evaluated in a cross-sectional study in which their clinical, ethnic and Demographic characteristics were collected. All patients underwent duplex ultrasound examination of their carotid vessels to obtain IMT measurements. RESULTS: One hundred and fifty-three patients (74.3%) had a carotid IMT greater than 1.0 mm at one or more point of measurement in at least one common carotid artery. There was a significant correlation between older age and mean carotid wall thickness (R=0.479 / P<0.01). Multivariate analysis identified male sex, arterial hypertension and older age as variables associated with increased IMT (P<0.05 for all variables). When IMT was compared between the two ethnic groups in this study, no significant differences were noted. Euro-descendants and Afro-descendants had similar IMT values, even when the groups were stratified by degree of IMT (normal vs. increased) and presence of stroke and/or transient ischemic attack (yes vs. no). CONCLUSIONS: The risk factors associated with increased common carotid artery IMT in Brazilian individuals are similar to those in previously described populations. No differences were observed between the two main Brazilian ethnic groups. Longitudinal studies are required for a better evaluation of the incidence, etiologic factors and evolution of carotid intimomedial thickening in this population.

Artéria femoral profunda: uma opção como origem de fluxo para derivações infrageniculares / Deep femoral artery: an option as inflow site in infragenicular bypasses

CONTEXTO: Na isquemia crítica, a artéria femoral profunda pode tornar-se a opção mais distal como origem de fluxo para derivações distais em casos de oclusão da origem da artéria femoral superficial associada a prega inguinal hostil. OBJETIVO:Avaliar, retrospectivamente, a artéria femoral profunda como doadora de fluxo para derivações infrageniculares. MÉTODOS: De 2000 a 2005, 129 derivações infrageniculares apresentaram anastomose proximal nas artérias femorais, comum (40), superficial (72) e profunda (17). O presente estudo teve como foco a artéria femoral profunda, e suas indicações foram: prega inguinal hostil (seis casos), limite da extensão do substituto (seis casos) e ambos os fatores (outros cinco casos). Foram abordadas a primeira e a segunda porção em 12 casos e a terceira porção em cinco casos. As cirurgias foram secundárias em 47% dos casos, e os substitutos utilizados foram veias do membro superior em 11 casos, safena interna em cinco e safena externa em um caso. RESULTADOS: No total dos enxertos (129), as estimativas de perviedade primária e salvamento do membro foram: 68,0% e 84,7%, respectivamente, com erro padrão (EP) aceitável (0,1) em 36 meses. Quando o grupo foi estratificado, as artérias femorais comum, superficial e profunda apresentaram resultados comparáveis de perviedade primária (63,3, 70,2 e 64,7%; p = 0,63) e salvamento do membro (83,1, 82,4 e 92,3%; p = 0,78). A perviedade dos enxertos com origem nas porções proximal e distal da artéria femoral profunda, bem como das cirurgias primárias e secundárias, foram comparáveis, sem diferença estatística significante (p = 0,89 e p = 0,77, respectivamente). CONCLUSÃO: A artéria femoral profunda mostrou ser acessível e efetiva como origem de fluxo de enxertos infrageniculares, com resultados satisfatórios de perviedade e salvamento do membro.

BACKGROUND: Deep femoral artery can be the most distal technical option as donor site in patients with critical limb ischemia presenting superficial artery occlusion and hostile groins. OBJECTIVE: To retrospectively assess the deep femoral artery as an inflow site for infragenicular bypass grafts. METHODS: From 2000 to 2005, 129 infragenicular bypass grafts with proximal anastomosis located in femoral arteries were performed. Forty were located in the common femoral artery (CFA), 72 in the superficial femoral artery (SFA) and 17 in the deep femoral artery (DFA). Indications for using the DFA as inflow were hostile groin (six cases), limited arterial substitute length (six cases) or both (five cases). Anastomosis site was located in the first or second portion in 12 cases, and in the third in five cases. The surgery was secondary in 47% of the cases, and the arterial substitutes used were arm veins (11), greater saphenous vein (five) and lesser saphenous vein (one). RESULTS: Primary patency and limb salvage rates were 68.0 and 84.7%, respectively, with acceptable standard error (0.1) in 36 months. The results of patency divided by inflow artery were similar (CFA, 63.3%; SFA, 70.2%; DFA 64.7%; p = 0.63), as well as limb salvage rates (CFA, 83.1%; SFA, 82.4%; DFA 92.3%; p = 0.78). Analyzing the deep femoral group, no difference of patency rates was observed when the anastomotic site was compared (proximal vs. distal portions of the DFA) or between patients with or without previous grafts. (p = 0.89 and 0.77, respectively). CONCLUSION: Deep femoral artery is a feasible and effective option as donor site for infragenicular bypass grafts, with satisfactory patency and limb salvage rates.

A practical protocol to measure common carotid artery intima-media thickness

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Late results of catheter-directed recombinant tissue plasminogen activator fibrinolytic therapy of iliofemoral deep venous thrombosis

PURPOSE: To evaluate the efficacy of catheter-directed low-dose recombinant tissue-type plasminogen activator infusion in the treatment of iliofemoral deep venous thrombosis and prevention of post-thrombotic syndrome. METHOD: Eighteen patients (out of 260 evaluated) with acute iliofemoral deep venous thrombosis and no previous evidence of venous insufficiency were prospectively selected for thrombolytic therapy. Catheter-directed low-dose recombinant tissue-type plasminogen activator (1 mg/h) was infused into the thrombotic segments. RESULTS: Effective fibrinolysis was achieved in 14 of 18 cases, with correlation between effective fibrinolysis and major/complete resolution of acute signs and symptoms (P <.01). There were no episodes of major complications. Four patients presented with early rethrombosis (1 to 8 weeks). Individuals were followed for a period up to 131 weeks (average, 85.2). The incidence of clinical signs and symptoms of venous insufficiency and duplex-scan findings of valvular reflux was significantly lower in the patients in which lytic therapy succeeded and patency was kept, compared with patients experiencing acute therapeutic failure or rethrombosis (P <.01). CONCLUSIONS: Low-dose recombinant tissue-type plasminogen activator fibrinolytic therapy is safe and effective in the treatment of acute iliofemoral venous thrombosis. The late evolution as revealed clinically and by ultrasound was superior in patients for whom lytic therapy was effective.

OBJETIVOS: Avaliar a eficácia da infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante em baixas doses no tratamento da trombose venosa iliacofemoral e na prevenção da síndrome pós-trombótica. MÉTODO: Dezoito pacientes (de 260 avaliados) portadores de trombose venosa profunda iliacofemoral sem evidência prévia de insuficiência venosa foram selecionados para terapia fibrinolítica e submetidos a infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante na dose de 1mg/dl nos segmentos venosos trombóticos. RESULTADOS: Quatorze pacientes apresentaram fibrinólise efetiva; observamos correlação entre o grau de melhora clínica observado e a redução percentual do volume trombótico (P<.01). Não houve episódios de complicações graves. Quatro pacientes apresentaram retrombose precoce (1 a 8 semanas). Os pacientes foram seguidos por um período de até 131 semanas (média 85.2). A incidência de sinais e sintomas clínicos de insuficiência venosa e os achados ecográficos de refluxo valvular foram significativamente menores nos pacientes em que a terapia fibrinolítica foi efetiva e a perviedade mantida ao longo do período de seguimento, na comparação com os casos de falha aguda ou de retrombose precoce (P<.01). CONCLUSÕES: A terapia fibrinolítica da trombose venosa iliacofemoral com ativador de plasminogênio tecidual recombinante seletivo em baixas doses demonstrou-se eficaz e segura. A evolução clínica e ecográfica tardia foi superior nos pacientes em que a terapia lítica foi efetiva.

Resultados do tratamento fibrinolítico da trombose venosa iliacofemoral por infusão seletiva de rt-PA em baixas doses / Results of fibrinolytic treatment of iliofemoral deep vein thrombosis by selective infusion of low-dose rt-PA

Avaliação imediata e tardia da terapia fibrinolítica da trombose venosa profunda iliacofemoral por infusão seletiva de rt-PA em baixas doses. Os pacientes foram submetidos à infusão transcateter de rt-PA (1mg/hora) nos segmentos venosos trombóticos, por um tempo médio de 41 horas. Houve fibrinólise efetiva em 12 dos 15 casos, com correlação entre o percentual de fibrinólise e a magnitude da melhora clínica aguda / Early and late evaluation of fibrinolytic therapy of iliofemoral deep venous thrombosis by selective infusion of low-dose rt-PA. Patients were submitted to transcatheter infusion of rt-PA (1mg/kg) in the thrombotic venous segments, with a mean lysis time of 41 hours. Effective lysis was reached in 12 of 15 cases. Statistic correlation between lysis grade and acute clinical improvement was observed...