¿El pretratamiento en los SCASEST recomendado por las guías es lo que refleja el mundo real? / Is the NSTEACS pretreatment recommended by the guidelines what reflects the real world?

Resumen El momento adecuado para la administración de los inhibidores P2Y12 en pacientes con síndrome coronario agudo sin elevación del segmento ST es tema de debate desde hace dos décadas. Las recomendaciones actuales de las guías europeas sugieren administrar ácido acetilsalicílico y aguardar el momento de la cinecoronariografía, y una vez conocida la anatomía agregar un inhibidor P2Y12 solo en aquellos casos en que se programe una estrategia intervencionista precoz. Sin embargo, en el mundo real la estrategia de realizar o no pretratamiento es más compleja. Existe la incertidumbre respecto a que el paciente pueda acceder o no a una cinecoronariografía dentro de las 24 horas. En este escenario, el pretratamiento al ingreso de un paciente de riesgo intermedio o alto podría ser una opción si no va a ser estudiado con cateterismo dentro de las 2 a 4 horas del ingreso, analizando previamente el riesgo isquémico y de sangrado del paciente. Aún faltan estudios a gran escala que comparen estas dos opciones.

Abstract The appropriate time for the administration of P2Y12 inhibitors in patients with non-ST elevation acute coronary syndrome has been the subject of debate for two decades. The current recommendations of the European guidelines suggest administering acetylsalicylic acid and waiting for the coronary angiography and once the anatomy is known, adding a P2Y12 inhibitor only in those cases in which an early interventional strategy is scheduled. However, in the real world, the strategy to perform pretreatment or not is more complex. There is uncertainty regarding whether the patient can access a coronary angiography within 24 hours. In this scenario, pretreatment upon admission of intermediate or high-risk patients could be an option if it is not studied with catheterization within 2 to 4 hours of admission, previously analyzing the patient's ischemic and bleeding risk. Large-scale studies comparing these two options are still lacking.

[Is the NSTEACS pretreatment recommended by the guidelines what reflects the real world?] / ¿El pretratamiento en los SCASEST recomendado por las guías es lo que refleja el mundo real?

The appropriate time for the administration of P2Y12 inhibitors in patients with non-ST elevation acute coronary syndrome has been the subject of debate for two decades. The current recommendations of the European guidelines suggest administering acetylsalicylic acid and waiting for the coronary angiography and once the anatomy is known, adding a P2Y12 inhibitor only in those cases in which an early interventional strategy is scheduled. However, in the real world, the strategy to perform pretreatment or not is more complex. There is uncertainty regarding whether the patient can access a coronary angiography within 24 hours. In this scenario, pretreatment upon admission of intermediate or high-risk patients could be an option if it is not studied with catheterization within 2 to 4 hours of admission, previously analyzing the patient's ischemic and bleeding risk. Large-scale studies comparing these two options are still lacking.

El momento adecuado para la administración de los inhibidores P2Y12 en pacientes con síndrome coronario agudo sin elevación del segmento ST es tema de debate desde hace dos décadas. Las recomendaciones actuales de las guías europeas sugieren administrar ácido acetilsalicílico y aguardar el momento de la cinecoronariografía, y una vez conocida la anatomía agregar un inhibidor P2Y12 solo en aquellos casos en que se programe una estrategia intervencionista precoz. Sin embargo, en el mundo real la estrategia de realizar o no pretratamiento es más compleja. Existe la incertidumbre respecto a que el paciente pueda acceder o no a una cinecoronariografía dentro de las 24 horas. En este escenario, el pretratamiento al ingreso de un paciente de riesgo intermedio o alto podría ser una opción si no va a ser estudiado con cateterismo dentro de las 2 a 4 horas del ingreso, analizando previamente el riesgo isquémico y de sangrado del paciente. Aún faltan estudios a gran escala que comparen estas dos opciones.

Antitrombóticos en las prótesis valvulares biológicas: ¿cuál es el mejor camino a seguir? / Antithrombotics in biological valve prostheses: what is the best way forward? / Antitrombóticos em próteses de válvulas biológicas: qual é o melhor caminho a seguir?

La enfermedad valvular cardíaca es una condición muy frecuente en la población general y un porcentaje considerable de estos pacientes requieren un tratamiento intervencionista sobre su valvulopatía para lograr atenuar su evolución natural. En este contexto, en la actualidad ha aumentado el uso de las prótesis valvulares biológicas para su tratamiento y, con ello, surge el dilema del manejo antitrombótico en estos pacientes en términos de prevención de tromboembolias y eventos hemorrágicos. ¿Cuál es el fármaco más efectivo y seguro en el período posoperatorio temprano? ¿Qué antitrombóticos podemos utilizar en el período posoperatorio tardío? ¿Qué estrategia seguimos cuando el paciente presenta otras indicaciones de anticoagulación? El objetivo de esta revisión es valorar la evidencia actual respecto al tratamiento antitrombótico en pacientes portadores de prótesis valvulares biológicas con y sin indicaciones adicionales de anticoagulación.

Heart valve disease is a very common condition in the general population and a considerable percentage of these patients require interventional treatment for their valve disease to mitigate its natural evolution. In this context, the use of biological prosthetic valves for their treatment has now increased, and with this, the dilemma of antithrombotic management in these patients arises, in terms of prevention of thromboembolism and hemorrhagic events. What is the most effective and safe drug in the early postoperative period? What antithrombotics can we use in the late postoperative period? What strategy do we follow when the patient presents other indications for anticoagulation? The objective of this review is to assess the current evidence regarding antithrombotic treatment in patients with biological prosthetic valves with and without additional indications for anticoagulation.

A valvopatia é uma condição muito comum na população geral e uma porcentagem considerável desses pacientes necessita de tratamento intervencionista para sua valvopatia para amenizar sua evolução natural. Nesse contexto, o uso de próteses valvares biológicas para seu tratamento tem aumentado, e com isso surge o dilema do manejo antitrombótico nesses pacientes em termos de prevenção de tromboembolismo e eventos hemorrágicos. Qual é o fármaco mais eficaz e seguro no pós-operatório imediato? Que antitrombóticos podemos usar no pós-operatório tardio? Que estratégia seguimos quando o paciente apresenta outras indicações de anticoagulação? O objetivo desta revisão é avaliar as evidências atuais sobre o tratamento antitrombótico em pacientes com próteses valvares biológicas com e sem indicações adicionais de anticoagulação.

Trombose Venosa Cerebral Acometendo Seio Transverso em Paciente Pediátrico: Relato de Caso e Revisão de Literatura / Cerebral Venous Thrombosis Occuring in a Transverse Sinus in Pediatric Patient: Case Report and Literature Review

Objetivo: A trombose venosa cerebral é um tipo raro de doença cerebrovascular que acomete todas as idades, sendo extremamente rara, em crianças. O objetivo deste trabalho foi relatar um caso de trombose venosa cerebral acometendo seio transverso em uma paciente de 3 anos. Métodos: Trata-se de uma pesquisa qualitativa, descritiva e exploratória, do tipo Relato de caso, realizada por meio da coleta de dados clínicos, laboratoriais e radiológicos em prontuário no Hospital Universitário Santa Terezinha ­ HUST. Resultados: Paciente, com 3 anos, apresentava cefaleia, vômitos, anorexia e sonolência há 4 dias. Na admissão em emergência, foram realizados exames laboratoriais e exames de imagem, tomografia computadorizada de crânio e angiorressonância cerebral, os quais confirmaram o diagnóstico de trombose venosa cerebral. Na discussão entre vascular, neurocirurgião e pediatra, optou-se pelo tratamento conservador com anticoagulante Enoxaparina, apresentando melhora significativa na clínica e na angiorressonância após 30 dias de tratamento. Conclusão: Apesar de ser rara em crianças, a suspeita clínica é fundamental para o diagnóstico precoce, e posterior estabelecimento de condutas adequadas, a fim de evitar complicações e reduzir a mortalidade. Não há consenso na literatura sobre o uso dos antitrombóticos, porém estudos mostram efeitos benéficos.

Objective: Cerebral venous thrombosis is a rare type of cerebrovascular disease that affects all ages, and is extremely rare in children. The objective of this study was to report a case of cerebral venous thrombosis affecting the transverse sinus of a 3-year-old patient. Methods: This is a qualitative, descriptive, and exploratory study of the case report type, carried out by collecting clinical, laboratory, and radiological data from medical records at the Santa Terezinha University Hospital (Hospital Universitário Santa Terezinha [HUST]). Results: A 3-year-old patient presented headache, vomiting, anorexia, and somnolence for four days. On emergency admission, laboratory tests and imaging exams, skull computed tomography, and cerebral angioresonance were performed, which confirmed the diagnosis of cerebral venous thrombosis. In the discussion between the vascular, the neurosurgeon, and the pediatrician, conservative treatment with anticoagulant Enoxaparin was chosen, showing significant improvement in clinical and angioresonance after 30 days of treatment. Conclusion: Despite being rare in children, clinical suspicion is essential for early diagnosis and the subsequent establishment of appropriate conduct to avoid complications and reduce mortality. There is no consensus in the literature on using antithrombotic agents, but studies show beneficial effects.

Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential.

Snake venom metalloproteinases (SVMPs) are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogen)olytic activity. Their main biological substrate is fibrin(ogen), whose Aα-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a) they are insensitive to plasma serine proteinase inhibitors; (b) they have the potential to avoid bleeding risk; (c) mechanistically, they are inactivated/cleared by α2-macroglobulin that limits their range of action in circulation; and (d) few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure-function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.

Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects?

The serotonin transporter (SERT) is found in neuron and platelet membranes. Selective serotonin-reuptake inhibitors (SSRIs) are widely prescribed for severe depression. They may at least partly counteract the effects of serotonin on the vascular biology system, can lower agonists-induced platelet activation, aggregation and procoagulant activity in vitro, thus modulating platelet thrombogenicity. Other effects, such as those mediated through PAI-1 modulation, may indirectly influence neurobiology-relevant mechanisms involved in depression. Patients receiving SSRIs are at increased bleeding risk and decreased risk of arterial occlusive events, such as myocardial infarction, compared to those using non-SSRI antidepressants. The objectives of this review were to highlight antiplatelet and profibrinolytic properties of SSRIs and discuss the potential role of these activities in the context of SSRI brain effects.

The case for an elderly targeted stroke management.

Stroke is a leading cause of death and disability worldwide. The elderly, in whom atrial fibrillation (AF) is most prevalent, carry the greatest risk, undergoing more recurrent, deadlier strokes, with bigger deficits, slower recoveries, and more comorbidities. Evidence-based data on advanced age stroke management are scarce. Age-related cerebral changes might undermine the benefit of established stroke treatments. Nevertheless, the elderly should probably also undergo thrombolysis for ischemic stroke: they do not bleed more, and die not because of hemorrhage but of concomitant illnesses. Beyond natural bleeding risks, AF in advanced age has a high embolic potential if not anticoagulated. Standard or lower intensity warfarin anticoagulation prevents embolic stroke in the elderly with a hemorrhage risk even lower than aspirin. In fact, adverse effects seem to occur more often with aspirin. Excess anticoagulation hazards are prevented with lower starting doses, stricter corrections, more frequent International Normalized Ratio monitoring, and longer adjustment intervals. Validated prognostic scores such as CHADS(2) help minimize bleeds. Direct inhibitors have recently shown a benefit similar to warfarin with fewer hemorrhages. Carefully tailoring antithrombotics to this age group is therefore useful. Antihypertensives probably help 80-plus stroke patients as well, but the risk/benefit of lowering blood pressure in secondary stroke prevention at that age is uncertain. Evidence-based data on diabetes management and use of lipid-lowering drugs are still lacking in this age group. In summary, emerging data suggest that stroke management should be specifically targeted to the elderly to better prevent its devastating consequences in the population at the highest risk.

Novas evidências em antitrombóticos na fibrilação atrial 2010 / New evidences in antithrombotics for atrial fibrillation 2010

JUSTIFICATIVA E OBJETIVOS: A principal arritmia cardíaca em pacientes acima dos 60 anos de idade é a fibrilação atrial (FA). Com o aumento da expectativa de vida, estima-se que 30% da população acima de 65 anos, apresentará FA, e esta é associada a um risco de eventos cardio embólicos anuais ao redor de 6% ao ano. Devido as complicações cardio embólicas, o tratamento de eleição é o uso de fármacos antitrombóticos, os quais estão incluídos, os antiplaquetários e os anticoagulantes, baseados na estratificação de risco do paciente. Até o momento, a terapia de eleição na prevenção de eventos cardio embólicos são os antagonistas de vitamina K (AVK); entretanto, devido sua janela terapêutica estreita, controle laboratorial rigoroso, interação com outros medicamentos e principalmente dificuldade de utilização em pacientes idosos, torna-se um fator limitador na prática clínica diária. Dentro deste cenário, novos antitrombóticos estão sendo desenvolvidos no intuito de melhorar o cuidado e a qualidade de vida dos portadores de FA e talvez substituir os AVK. CONTEÚDO Artigos publicados entre 1969 e 2009 foram selecionados no banco de publicações Medline, através das palavras-chaves fibrilação atrial, antitrombóticos, anticoagulantes e antiplaquetários, assim como diretrizes internacionais foram buscadas no link http://sumsearch.uthscsa.edu. CONCLUSÃO: O desenvolvimento de novos antitrombóticos, através de ensaios clínicos aleatórios, talvez em um futuro próximo possibilite a utilização e implementação de forma sistemática na pratica clinica destes novos medicamentos, como, por exemplo, os inibidores diretos da trombina, inibidores diretos e indiretos do fator Xa, superando as limitações dos AVK.(AU)

BACKGROUND AND OBJECTIVES: The main cardiac arrhythmia in patients over 60 years of age is atrial fibrillation (AF). With increasing life expectancy, it is estimated that 30% of the population over 65 years, will present FA, and this is associated with a risk of cardioembolic events annually around 6% per annum. Because of cardioembolic complications, the treatment of choice is the use of antithrombotic drugs, which are included, the antiplatelet agents and anticoagulants, based on risk stratification of patients. So far, the therapy of choice in the prevention of cardioembolic events are antagonists of vitamin K (AVK), however, due to its narrow therapeutic window, under strict control, interaction with other drugs and especially difficult to use in elderly patients, it is a limiting factor in clinical practice. Within this scenario, new antithrombotic agents are being developed in order to improve care and quality of life of patients with AF and perhaps replace the AVK. The development of new antithrombotic drugs through clinical trials, perhaps in the near future allow the use and implementation in a systematic manner in the clinical practice of these new drugs, such as the direct thrombin inhibitors, indirect and direct inhibitors of factor Xa, overcoming limitations of AVK.CONTENTS: Articles published from 1969 to 2009 were selected in the MedLine database, using the keywords Atrial Fibrillation, antithrombotics, anticoagulants, antiplatelets in the MedLine database as well as search for international guidelines in http://sumsearch.uthscsa.edu.CONCLUSION: The development of new antithrombotic drugs through clinical trials, perhaps in the near future allow the use and implementation in a systematic manner in the clinical practice of these new drugs, such as the direct thrombin inhibitors, indirect and direct inhibitors of factor Xa, overcoming limitations of AVK.(AU)

Tratamiento combinado con antitrombóticos en la prevención secundaria del ictus isquémico: [revisión] / Combined treatment with antithrombotics in secondary prevention of the isquemic stroke: [review]

El ictus isquémico constituye un problema sanitario de primer orden debido a su alto riesgo de recurrencia. La búsqueda de estrategias eficaces y seguras para la prevención de eventos vasculares en los pacientes con un ictus isquémico debe ser una prioridad, con el objetivo de disminuir la mortalidad y discapacidad asociada con el mismo. Diversos estudios han analizado el tratamiento combinado con antitrombóticos para intentar mejorar la eficacia de estos fármacos en la prevención secundaria de eventos vasculares tras un primer ictus isquémico. En este trabajo se revisa el estado actual de la evidencia científica en cuanto a la terapia combinada con antitrombóticos en pacientes con un primer ictus isquémico...

Ischemic stroke constitutes a fundamental health issue due to its high level of recurrence. Developing efficient and safe strategies to prevent vascular episodes in patients with ischemic stroke must be a top priority, with the purpose of diminishing associated mortality and disability. Several studies have examined combined antithrombotic therapy in depth, trying to improve its efficacy in secondary prevention of vascular events after a first ischemic stroke. This work reviews the current state of clinical evidence related to combined antithrombotic therapy in patients presenting a first ischemic stroke...

Antitrombóticos nas síndromes coronarianas agudas: diretrizes atuais e novas evidências / Antithrombotics in acute coronary syndromes: actual guidelines and new evidences

JUSTIFICATIVA E OBJETIVOS: As síndromes coronarianas agudas (SCA) estão entre as principais causas de admissão em unidades de terapia intensiva (UTI). Novos fármacos vêem sendo desenvolvidos para o manuseio das SCA. O uso combinado destes medicamentos tem reduzido de forma considerável a morbimortalidade desta síndrome, no entanto seus efeitos adversos ou mesmo seu manuseio incorreto podem levar à maior incidência de sangramento. O objetivo deste estudo foi apresentar os principais aspectos terapêuticos, indicações e manuseio dos fármacos em síndromes coronárias agudas. MÉTODO: Foi realizada uma busca por artigos originais cruzando os unitermos acute coronary syndromes e antitrombotic therapy na base de dados -MedLine; busca de artigos e diretrizes nacionais e internacionais no endereço eletrônico: http://sumsearch.uthscsa.edu. RESULTADOS: No tratamento de angina instável e infarto sem supradesnivelamento de ST, a enoxaparina mostrou-se tão eficaz quanto à heparina não fracionada (HNF) e de manuseio mais simples (estudos SYNERGY e A a Z). Neste cenário, o fondaparinux também não foi inferior à enoxaparina e; no entanto, promoveu menor taxa de sangramento (OASIS-5), a bivalirudina também foi não inferior combinada ou não à GPIIB/IIIa comparada a outras heparinas (ACUITY). No infarto com supradesnivelamento do segmento ST, a enoxaparina foi superior à HNF em pacientes submetidos à trombólise (EXTRACT TIMI 25), e no estudo OASIS 6, o fondaparinux foi superior à HNF em pacientes submetidos à trombólise e os não submetidos à reperfusão. CONCLUSÕES: A correta administração das doses dos antitrombóticos e a escolha individualizada da combinação de fármacos são imprescindíveis para a redução de óbito e eventos cardiovasculares maiores, reduzindo o desconfortável risco de sangramento adicional.

BACKGROUND AND OBJECTIVES: Acute coronary syndromes (ACS) are one of the most common causes of ICU admissions. New drugs have been developed for management of ACS. These drugs reduced morbidity and mortality; however their adverse effects or their incorrect use may cause excessive bleeding. The objective of this review is to present the principal peculiarities, doses, and indications of these drugs in ACS settings. METHODS: Original articles were retrieved crossing the terms acute coronary syndromes and antithrombotic therapy in the MedLine database as well as search for Brazilian and international guidelines in http://sumsearch.uthscsa.edu. RESULTS: In the treatment of acute coronary syndromes with non-ST-segment elevation enoxaparin was as efficient as UFH, but with a simpler management (SYNERGY and A to Z studies). In this same setting, fondaparinux was non inferior to enoxaparin and had lesser bleedings (OASIS 5), bivalirudin, combined or not with GPIIbIIIa blockers, was not inferior when compared with other heparins (ACUITY). In ST-segment elevation ACS, enoxaparin was superior to HNF in patients treated with fibrinolysis (EXTRACT TIMI 25); in OASIS 6 fondaparinux was superior to UFH in patients treated with thrombolytic therapy and not submitted to reperfusion. CONCLUSIONS: The correct management and individual combination of antithrombotic drugs are mandatory for decreased mortality and of major cardiovascular events, reducing the undesirable risk of additional bleeding.