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INTRODUCTION: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. ethod: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies. The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of primary hemostasis and blood coagulation. The compounds that showed inhibition greater than 85% were submitted to the analysis of their potency by calculating the concentration required to inhibit 50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent with IC50 of 1.45 µM. Interestingly, this derivative inhibited more than 90% of platelet aggregation induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay, most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally, the compounds tested at 100 µM also showed no cytotoxic effects in HepG2 and Vero cells. RESULT: The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR, which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity. CONCLUSION: Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates for the development of novel antiplatelet agents.
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Resumen El número de personas en tratamiento con fármacos anticoagulantes o antiplaquetarios está en crecimiento constante debido al aumento de la supervivencia de los pacientes con fibrilación auricular, válvulas cardiacas mecánicas o que han sufrido un evento isquémico o trombótico agudo. Cuando estos pacientes necesitan un procedimiento radiológico intervencionista que acarrea riesgo de sangrado, es necesario analizar el riesgo trombótico del paciente al interrumpir la medicación frente al riesgo hemorrágico del procedimiento para tomar la decisión más adecuada en cada caso. Por tanto, es una decisión individualizada y supone un desafío para los/as radiólogos/as que realicen estas técnicas. Nuestro objetivo en esta revisión es mostrar las recomendaciones actuales sobre el manejo perioperatorio de la medicación anticoagulante y antiplaquetaria, adaptada al intervencionismo radiológico.
Abstract The number of people treated with anticoagulant or antiplatelet agents is constantly growing due to the increased survival of patients with atrial fibrillation, mechanical cardiac valves or who have suffered an acute thrombotic or ischemic event. When these patients need an interventional radiological procedure that carries a risk of bleeding, it is necessary to analyze the thrombotic risk of the patient when interrupting the medication against the hemorrhagic risk of the procedure, to make the most appropriate decision in each case. Therefore, it is an individualized decision, and it is a challenge for radiologists who perform these techniques. Our goal in this review is to update the current recommendations on the perioperative management of anticoagulant and antiplatelet agents, adapted to the radiological interventionism.
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This review is an update on antiplatelet therapy and its interaction with oral hypoglycemic agents in diabetic patients with ischemic heart disease. We summarize the main pathophysiological mechanisms that intervene in diabetic patients and that increase the ischemic risk, the effects of the combination of oral hypoglycemic agents, their antithrombotic effects and their interaction with antiplatelet, and finally the studies that demonstrated the benefits of antiplatelet in diabetic patients in different scenarios of ischemic heart disease. The different mechanisms of action involve improved glycemic control, increased bioavailability of nitric oxide, reduced oxidative stress and, for certain molecules, direct inhibition of platelet activation and aggregation.
Esta revisión consiste en una puesta al día del tratamiento antiplaquetario y la interacción que presenta con los hipoglucemiantes orales en pacientes diabéticos con cardiopatía isquémica. Resumimos los principales mecanismos fisiopatológicos que intervienen en el aumento del riesgo cardiovascular en este grupo, los efectos de la combinación entre los hipoglucemiantes orales, sus efectos antitrombóticos y su interacción con los antiplaquetarios y, por último, los trabajos que estudiaron los beneficios de los antiplaquetarios en pacientes diabéticos en diferentes escenarios de la cardiopatía isquémica. Los variados mecanismos de acción implican una mejora del control de la glucemia, del aumento de la biodisponibilidad del óxido nítrico, reducción del estrés oxidativo y, para ciertas moléculas, una inhibición directa de la activación y de la agregación plaquetaria.
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Isquemia Miocárdica , Inibidores da Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Fibrinolíticos/efeitos adversos , Hipoglicemiantes/efeitos adversos , Anticoagulantes/uso terapêutico , Quimioterapia CombinadaRESUMO
Resumen Esta revisión consiste en una puesta al día del tratamiento antiplaquetario y la interacción que presenta con los hipoglucemiantes orales en pacientes diabéticos con cardiopatía isquémica. Re sumimos los principales mecanismos fisiopatológicos que intervienen en el aumento del riesgo cardiovascular en este grupo, los efectos de la combinación entre los hipoglucemiantes orales, sus efectos antitrombóticos y su interacción con los antiplaquetarios y, por último, los trabajos que estudiaron los beneficios de los antiplaque tarios en pacientes diabéticos en diferentes escenarios de la cardiopatía isquémica. Los variados mecanismos de acción implican una mejora del control de la glucemia, del aumento de la biodisponibilidad del óxido nítrico, reducción del estrés oxidativo y, para ciertas moléculas, una inhibición directa de la activación y de la agregación plaquetaria.
Abstract This review is an update on antiplatelet therapy and its interaction with oral hypoglycemic agents in diabetic patients with ischemic heart disease. We summarize the main pathophysiological mechanisms that intervene in diabetic patients and that increase the ischemic risk, the effects of the combination of oral hypoglycemic agents, their antithrombotic ef fects and their interaction with antiplatelet, and finally the studies that demonstrated the benefits of antiplatelet in diabetic patients in different scenarios of ischemic heart disease. The different mechanisms of action involve improved glycemic control, increased bioavailability of nitric oxide, reduced oxidative stress and, for certain mol ecules, direct inhibition of platelet activation and aggregation.
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Debido a sus metabolitos secundarios, las plantas medicinales presentan diversas acciones farmacológicas que posibilitan la elaboración de productos naturales. En el presente trabajo se describen, brevemente, las actividades con utilidad en las afecciones hematológicas e inmunológicas. Para ello se realizó una revisión actualizada de las investigaciones científicas acerca de esta temática, lo cual permitió concluir que el empleo de productos naturales, como tratamiento adyuvante, favorece adecuadamente a los pacientes con enfermedades hematológicas e inmunológicas(AU)
Due to their secondary metabolites, medicinal plants have various pharmacological actions that enable the development of natural products. In the present work, the activities useful in hematological and immunological conditions are briefly described. For this, an updated review of the scientific research on this subject was carried out, which allowed the conclusion that the use of natural products, as adjuvant treatment, adequately benefits patients with hematological and immunological diseases(AU)
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Humanos , Masculino , Feminino , Produtos Biológicos , Ações Farmacológicas , Doenças do Sistema Imunitário , PesquisaRESUMO
INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.
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Anemia Falciforme/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Ticagrelor/uso terapêutico , Anemia Falciforme/sangue , Coagulação Sanguínea/efeitos dos fármacos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Monitoramento de Medicamentos , Humanos , Estrutura Molecular , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2Y/química , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Trombofilia/prevenção & controle , Ticagrelor/química , Ticagrelor/farmacocinética , Resultado do TratamentoRESUMO
Resumen El uso de fármacos antiagregantes plaquetarios para prevención primaria y secundaria de eventos cardiovasculares es una práctica común en clínica. La terapia antiagregante plaquetaria disminuye significativamente la incidencia de eventos cardiovasculares, incluyendo infarto agudo al miocardio y accidente cerebro-vascular. Cada vez es más frecuente enfrentarse a pacientes en terapia antiagregante plaquetaria que serán sometidos a algún procedimiento quirúrgico, por tanto es fundamental conocer el manejo perioperatorio de estos fármacos, para disminuir los riesgos y complicaciones asociados a la suspensión o mantención de estas drogas en el período perioperatorio. Los antiagregantes plaquetarios de mayor uso en Chile son la aspirina y las tienopiridinas, siendo el clopidogrel el fármaco más utilizado en este grupo. El enfrentamiento perioperatorio de estos fármacos está supeditado al riesgo trombótico individual de cada paciente y al riesgo hemorrágico de cada cirugía. En cirugías no cardiacas, se sugiere mantener la aspirina, excepto en pacientes con bajo-moderado riesgo trombótico que serán sometidos a cirugías con alto riesgo de sangrado, en los cuales se recomienda suspenderla 5-7 días previo a la intervención quirúrgica. El clopidogrel se sugiere suspenderlo 5 días antes de la cirugía, excepto en pacientes con alto riesgo trombótico que se someterán a procedimientos quirúrgicos con riesgo hemorrágico bajo-moderado. En cirugías de revascularización miocárdica, se recomienda mantener aspirina y suspender clopidogrel 5 días antes del procedimiento. En relación al reinicio postquirúrgico de estos fármacos, se sugiere reanudar aspirina 6 h posterior a la cirugía y clopidogrel durante las primeras 24 h postoperatorias, asegurando previamente una adecuada hemostasia quirúrgica.
The use of antiplatelet drugs for primary and secondary prevention of cardiovascular disease events is a common clinical practice. Antiplatelet therapy significantly decreases the incidence of cardiovascular disease events, including acute myocardial infarction and cerebrovascular accident. It is increasingly common to face patients on antiplatelet therapy who will undergo some surgical procedure, so it is essential to know the perioperative management of these drugs, to reduce the risks and complications associated with the suspension or maintenance of these therapies in the perioperative period. The most common antiplatelet agents used in Chile are acetylsalicylic acid and thienopyridines, of which clopidogrel is the most frequent one. The perioperative management of these drugs has to be based on the individual thrombotic risk of each patient and the risk of hemorrhage of each surgery. In noncardiac surgeries, it is suggested to maintain acetylsalicylic acid, except in patients with low to moderate thrombotic risk who will undergo surgeries with a high risk of bleeding, in which case it is recommended to suspend it 5 to 7 days before surgery. Clopidogrel is suggested to be discontinued 5 days before surgery, except in patients with high thrombotic risk who will undergo surgical procedures with low to moderate risk of hemorrhage. In myocardial revascularization surgeries, it is recommended to maintain acetylsalicylic acid and to suspend clopidogrel 5 days before the procedure. Once assuring adequate surgical hemostasis, it is suggested to reinitiate acetylsalicylic acid 6 hours after surgery and to reinitiate clopidogrel during the first 24 postoperative hours.
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Humanos , Procedimentos Cirúrgicos Operatórios/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Assistência Perioperatória/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Medição de Risco , Hemorragia Pós-Operatória/induzido quimicamente , Suspensão de Tratamento , Tienopiridinas/administração & dosagem , Tienopiridinas/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversosRESUMO
BACKGROUND: Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. MAIN BODY: The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. CONCLUSIONS: Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.
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Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis.
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Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Mucosa Gástrica/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Adolescente , Adulto , Plaquetas/metabolismo , Método Duplo-Cego , Esquema de Medicação , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Paciente masculino de 65 años de edad, con antecedentes de habérsele colocado stent coronario y tratamiento antiagregante plaquetario con Aspirina® y Clopidogrel®. A los 21 días comenzó a presentar dolor en el flanco y la fosa ilíaca derechos, náuseas y vómitos. En el examen físico inicial se detectó dolor y aumento de volumen en las zonas referidas y los signos vitales normales. El ultrasonido abdominal reveló colección perirrenal derecha bien delimitada y riñones de tamaño y ecoestructura normal. La tomografía axial computarizada evidenció la presencia de una imagen renal subcapsular derecha, con densidades de líquido, con compresión extrínseca de un riñón estructuralmente normal. Al día siguiente del ingreso comenzó a presentar fiebre de 38 ºC. Se suspendió el tratamiento antiagregante plaquetario y a los 7 días se realizó lumbotomía y drenaje del hematoma; se obtuvo alrededor de 400 mL de sangre carmelitosa. El paciente evolucionó satisfactoriamente. Se concluye que el hematoma renal subcapsular espontáneo es una complicación inusual del uso de antiagregantes plaquetarios que necesita manejo multidisciplinario. La tomografía axial computarizada es indispensable para el diagnóstico imagenológico de certeza. La compresión renal por su gran tamaño, así como el dolor y la aparición de fiebre, justifican su drenaje quirúrgico.
A case of a 65 year-old male patient with a history of having received a coronary stent and antiplatelet therapy with Aspirin® and Clopidogrel® is presented here. He complained of pain in the right flank and iliac fossa nausea and vomiting 21 days after the procedure. At initial physical examination, normal vital signs but pain and increased volume in the aforementioned areas were detected. Abdominal ultrasound revealed well defined right perirenal collection and normal size kidneys and echotexture. Computed tomography showed the presence of a right subcapsular renal image with liquid density and extrinsic compression of a structurally normal kidney. The day after admission the patient ran a fever of 38 ºC. Antiplatelet therapy was discontinued and lumbotomy and drainage of the hematoma was performed 7 days latter; about 400 mL of brownish blood was obtained. The patient progressed satisfactorily. It is concluded that spontaneous subcapsular renal hematoma is a rare complication of antiplatelet requiring multidisciplinary management.Computed tomography imaging is required for diagnosis. The renal compression due to its large size as well as pain and fever, justify their surgical drainage.
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Humanos , Masculino , Idoso , Inibidores da Agregação Plaquetária/administração & dosagem , Isquemia Miocárdica/diagnóstico , Tomografia Computadorizada Espiral/métodos , Hipertensão/diagnóstico , RimRESUMO
Con el advenimiento de los antiplaquetarios se dio un gran avance en el tratamiento del infarto y el Accidente Vascular Cerebral. Con la combinación de los antiplaquetarios se potencia el efecto antitrombótico, mejorando los resultados y la reversión de los eventos, sin embargo, aumenta los efectos secundarios como el sagrado. Aproximadamente, existe alrededor de 20 fármacos antiplaquetarios, algunos se administran oral o intravenosamente como el tirofiban, abciximab, y la eptifibatida. En la presente revisión hablaremos solamente de la terapia oral de los principales antiplaquetarios orales, sus efectos secundarios, sus indicaciones y precauciones. Aunque, muchas veces se administra los medicamentos plaquetarios en dosis correctas no siempre se puede ver la recanalización del vaso sanguíneo debido a un síndrome de resistencia a los antiplaquetarios.
The advent of antiplatelet agents was a major advance in the treatment of thrombotic events, so that are revolutionizingthe treatment of heart attack and stroke. The combination of antithrombotic antiplatelet gave better effect andimprovement results and reverse of events. However, increases the side effects such as bleeding. Approximately existsaround twenty antiplatelet drugs, some are administered orally or intravenously as Tirofiban, Abciximab and Eptifibatide.In this review we will talk only therapy of oral antiplatelet main, side effects, indications and precautions. Although oftenadministrated the correct dose antiplatelet drugs, those can not always obtain the blood vessel recanalization due toresistance: syndrome antiplatelets.
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Humanos , Aspirina , Hemorragia , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/análise , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , TromboseRESUMO
Introducción El 30% de los pacientes presentan antiagregación plaquetaria inadecuada con 100 mg/día de aspirina (AAS) luego de la cirugía de revascularización miocárdica (CRM), que podría deberse a una acción inhibitoria menor de esta dosificación de AAS a la mayor activación plaquetaria y al aumento del recambio plaquetario que ocurren en el posoperatorio. Objetivos Evaluar la relación entre el recuento plaquetario y el menor efecto antiagregante y determinar si dosis fragmentadas de AAS mejoran la antiagregación. Material y métodos Luego de la CRM con bypass cardiopulmonar (2,95 puentes en promedio), se aleatorizaron prospectivamente 50 pacientes a tres grupos: 18 pacientes (G100) a 100 mg/día, 14 (G300) a 300 mg/día y 18 (G100Î3) a 100 mg 3 veces por día de AAS. En el preoperatorio todos recibieron 100 mg/día. La reactividad plaquetaria se midió mediante agregación en sangre entera con ácido araquidónico antes de la cirugía (T0), al primero (T1), tercero (T2) y séptimo días (T3) y al mes (T4) pos-CRM. Resultados En el preoperatorio todos los pacientes tenían valores óptimos de antiagregación (0 W). En el posoperatorio, los pacientes del G100Î3 tuvieron mejores niveles de antiagregación (p < 0,05). Ningún paciente del G100Î3 tuvo valores ≥ 6 W, correspondientes a los de personas sanas sin AAS, a diferencia de 5 pacientes (28%) del G100 y 4 pacientes (29%) del G300. Se observó una asociación estadísticamente significativa entre la antiagregación plaquetaria y el recambio del número de plaquetas (R2 = 0,57; p = 0,001). Un recambio diario > 20% se relacionó con valores de agregación plaquetaria ≥ 6 W con un OR = 2,1 (IC 1,8-4,21; p = 0,0028). Conclusiones En los pacientes sometidos a CRM, la menor respuesta antiagregante a la AAS se correlacionó con el recambio aumentado de plaquetas. El tratamiento podría fragmentarse con dosis bajas de AAS para obtener mejor antiagregación.(AU)
Thirty percent of patients do not achieve an adequate antiplatelet effect despite therapy with aspirin (ASA) 100 mg/d after coronary artery bypass-graft surgery (CABGS), probably due to reduced inhibitory effect of ASA, increased platelet activation and increased platelet turnover secondary to the surgical procedure. Objectives To evaluate the relation between platelet count and lower antiplatelet effect and to determine if antiaggregation improves by dividing the dose of ASA. Material and Methods A total of 50 patients undergoing CABGS (with an average of 2.95 grafts per surgery) were randomly assigned to three groups depending on the dose of ASA indicated: G100 (100 mg/d, n=18 patients), G300 (300 mg/d, n=14) and G100Î3 (100 mg TID, n=18). All the patients received 100 mg/d before surgery. Platelet reactivity was assessed by whole blood impedance using arachidonic acid before surgery (T0), 24 h (T1), 72 h (T2), 7 days (T3), and one month post-CABG (T4). Results Before surgery, all patients had optimal values of antiaggregation (0 W). During the postoperative period, antiaggregation values were better in patients from G100Î3 (p <0.05). No patients in G100Î3 had values ≥6 W, which correspond to those of healthy subjects who do not receive ASA. This value was observed in 5 patients (28%) from G100 and 4 patients (29%) from G300. The association between antiaggregation and platelet turnover was statistically significant (R2=0.57; p=0.001). A daily turnover >20% was related with values of platelet aggregation ≥6 W; OR=2.1 (CI 1.8-4.21; p=0.0028). Conclusions In patients undergoing CABGS, the lowest antiplatelet effect of ASA was associated with the highest platelet turnover. A better antiaggregation might be achieved by dividing therapy in low dose of ASA.(AU)
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Introducción El 30% de los pacientes presentan antiagregación plaquetaria inadecuada con 100 mg/día de aspirina (AAS) luego de la cirugía de revascularización miocárdica (CRM), que podría deberse a una acción inhibitoria menor de esta dosificación de AAS a la mayor activación plaquetaria y al aumento del recambio plaquetario que ocurren en el posoperatorio. Objetivos Evaluar la relación entre el recuento plaquetario y el menor efecto antiagregante y determinar si dosis fragmentadas de AAS mejoran la antiagregación. Material y métodos Luego de la CRM con bypass cardiopulmonar (2,95 puentes en promedio), se aleatorizaron prospectivamente 50 pacientes a tres grupos: 18 pacientes (G100) a 100 mg/día, 14 (G300) a 300 mg/día y 18 (G100×3) a 100 mg 3 veces por día de AAS. En el preoperatorio todos recibieron 100 mg/día. La reactividad plaquetaria se midió mediante agregación en sangre entera con ácido araquidónico antes de la cirugía (T0), al primero (T1), tercero (T2) y séptimo días (T3) y al mes (T4) pos-CRM. Resultados En el preoperatorio todos los pacientes tenían valores óptimos de antiagregación (0 W). En el posoperatorio, los pacientes del G100×3 tuvieron mejores niveles de antiagregación (p < 0,05). Ningún paciente del G100×3 tuvo valores ≥ 6 W, correspondientes a los de personas sanas sin AAS, a diferencia de 5 pacientes (28%) del G100 y 4 pacientes (29%) del G300. Se observó una asociación estadísticamente significativa entre la antiagregación plaquetaria y el recambio del número de plaquetas (R2 = 0,57; p = 0,001). Un recambio diario > 20% se relacionó con valores de agregación plaquetaria ≥ 6 W con un OR = 2,1 (IC 1,8-4,21; p = 0,0028). Conclusiones En los pacientes sometidos a CRM, la menor respuesta antiagregante a la AAS se correlacionó con el recambio aumentado de plaquetas. El tratamiento podría fragmentarse con dosis bajas de AAS para obtener mejor antiagregación.
Thirty percent of patients do not achieve an adequate antiplatelet effect despite therapy with aspirin (ASA) 100 mg/d after coronary artery bypass-graft surgery (CABGS), probably due to reduced inhibitory effect of ASA, increased platelet activation and increased platelet turnover secondary to the surgical procedure. Objectives To evaluate the relation between platelet count and lower antiplatelet effect and to determine if antiaggregation improves by dividing the dose of ASA. Material and Methods A total of 50 patients undergoing CABGS (with an average of 2.95 grafts per surgery) were randomly assigned to three groups depending on the dose of ASA indicated: G100 (100 mg/d, n=18 patients), G300 (300 mg/d, n=14) and G100×3 (100 mg TID, n=18). All the patients received 100 mg/d before surgery. Platelet reactivity was assessed by whole blood impedance using arachidonic acid before surgery (T0), 24 h (T1), 72 h (T2), 7 days (T3), and one month post-CABG (T4). Results Before surgery, all patients had optimal values of antiaggregation (0 W). During the postoperative period, antiaggregation values were better in patients from G100×3 (p <0.05). No patients in G100×3 had values ≥6 W, which correspond to those of healthy subjects who do not receive ASA. This value was observed in 5 patients (28%) from G100 and 4 patients (29%) from G300. The association between antiaggregation and platelet turnover was statistically significant (R2=0.57; p=0.001). A daily turnover >20% was related with values of platelet aggregation ≥6 W; OR=2.1 (CI 1.8-4.21; p=0.0028). Conclusions In patients undergoing CABGS, the lowest antiplatelet effect of ASA was associated with the highest platelet turnover. A better antiaggregation might be achieved by dividing therapy in low dose of ASA.
RESUMO
La fibrilación atrial es la taquiarritmia más prevalente en los adultos mayores. La frecuencia de dicha arritmia aumenta con la edad, presentándose en un 1.5 por ciento de los 50 a 59 años a 10 por ciento de los 80 a 89 años. La fibrilación atrial no valvular incrementa el riesgo de sufrir un evento cerebrovascular isquémico cardioembólico en 5 veces y causa el 15 por ciento de todos los accidentes cerebrovasculares isquémicos en Estados Unidos de América. El manejo de la fibrilación atrial se enfoca, principalmente, en la prevención de los fenómenos tromboembólicos y en el control de la frecuencia y ritmo cardiaco. La anticoagulación, cuando está indicada, ha demostrado ser la principal herramienta en la prevención de dichos eventos. Sin embargo, aunque las complicaciones hemorrágicas son más frecuentes, en esta población, y aumentan con la edad, sobrepasa por mucho, el beneficio al riesgo. El control de la frecuencia cardiaca ha demostrado ser igual o mejor que el control del ritmo en cuanto a prevención de eventos cerebrovasculares y mortalidad en estos pacientes. La edad cronológica por sí sola, no es contraindicación algun para ofrecer una terapia óptima. Debe tomarse en cuenta el estado funcional, cognitivo y social, así como aspectos fisiológicos del envejecimiento con respecto a la prescripción de medicamentos. Cuando, a pesar del tratamiento adecuado, la sintomatología persiste, las estrategias invasivas han demostrado ser beneficiosas, pero faltan estudios que involucren a individuos mayores.
Atrial fibrillation is the most prevalent arrhythmia in the elderly. Its frequency increases with age, being 1.5% from 50 to 59 years old and 10% from 80 to 89 years old. Non valvular atrial fibrillation increases 5 fold the risk of suffering an stroke and causes 15% of strokes in the USA. Atrial fibrillation management focuses in the prevention of thromboembolic phenomena andheart rate and rhythm control. Anticoagulation, when indicated, has demonstrated to be the main tool in the prevention of these events.Nevertheless, although bleeding complications are more frequent in this population and increase with age, anticoagulation benefits are greater than the risks. Heart rate control is better than rhythm control regarding cerebrovascular accidents and mortality. Age by itself is not acontraindication to offer optimal therapy. Functional, mental and social status, must be taken into account as well as physiological aspects of aging when it comes to prescribing medications. If symptoms persist in spite of adequate treatment, invasive strategies have demonstrated to beof benefit, however studies in elderly population are lacking.