Neutrophil-lymphocyte ratio and clinical outcomes in 19,697 patients with atrial fibrillation: Analyses from ENGAGE AF- TIMI 48 trial.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is the ratio between neutrophil and lymphocyte counts measured in peripheral blood. NLR is easily calculable based on a routine blood test available worldwide and may reflect systemic inflammation. However, the relationship between NLR and clinical outcomes in atrial fibrillation (AF) patients is not well-described. METHODS: We calculated NLR at baseline in ENGAGE AF-TIMI 48, a randomized trial comparing edoxaban versus warfarin in patients with AF followed for 2.8 years (median). The association of baseline NLR with major bleeding events, major adverse cardiac events (MACE), cardiovascular death, stroke/systemic embolism, and all-cause mortality were calculated. RESULTS: The median baseline NLR in 19,697 patients was 2.53 (interquartile range 1.89-3.41). NLR was associated with major bleeding events (HR 1.60; 95% CI 1.41-1.80), stroke/systemic embolism (HR 1.25; 95% CI, 1.09-1.44), MI (HR 1.73; 95% CI 1.41-2.12), MACE (HR 1.70; 95% CI 1.56-1.84), CV (HR 1.93; 95% CI 1.74-2.13) and all-cause mortality (HR 2.00; 95% CI 1.83-2.18). The relationships between NLR and outcomes remained significant after adjustment for risk factors. Edoxaban consistently reduced major bleeding. MACE, and CV death across NLR groups vs. warfarin. CONCLUSIONS: NLR represents a widely available, simple, arithmetic calculation that could be immediately and automatically reported during a white blood cell differential measurement to identify patients with AF at increased risk of bleeding, CV events, and mortality.

[Methotrexate-induced stroke-like syndrome: A pediatric case report]. / Encefalopatía subaguda reversible por metotrexato: notificación de un caso pediátrico.

Leukemias are the most frequent malignant neoplasms in childhood; acute lymphoblastic leukemia (ALL) is the most frequent. The addition of intrathecal methotrexate to chemotherapy regimens has been beneficial in preventing relapse to the central nervous system and avoiding the use of radiation therapy. Due to its mechanism of action, by inhibiting the enzyme dihydrofolate reductase, when it is used systemically, it has multiple expected adverse effects such as mucositis, myelosuppression and it has also been observed after intrathecal administration or high intravenous doses, acute, subacute neurotoxicity where stroke like syndrome is found. We present an 11-year-old patient diagnosed with T-ALL, who manifested after 8 days of intrathecal administration of methotrexate, faciobrachial hemiparesis and acute onset expression aphasia. The diagnosis of subacute encephalopathy reversible by methotrexate was reached by excluding other Encefalopatía subaguda reversible por metotrexato: notificación de un caso pediátrico Methotrexate-induced stroke-like syndrome: A pediatric case report more frequent pathologies and the typical evolution, with spontaneously ad integrum resolution of the symptoms.

Las leucemias son las neoplasias malignas más frecuentes en la infancia; la leucemia linfoblástica aguda (LLA) es la más frecuente. Desde principios de los 80, la adición de metotrexato intratecal a los esquemas de quimioterapia ha sido beneficiosa para prevenir la recidiva en el sistema nervioso central y evitar el uso de radioterapia. Su mecanismo de acción es la inhibición de la enzima dihidrofolato reductasa, por lo que posee múltiples efectos adversos (neurotoxicidad aguda, subaguda o crónica) después de la infusión intratecal o de dosis altas por vía intravenosa. Se presenta un paciente de 11 años con diagnóstico de LLA de línea T (LLA-T), que presenta hemiparesia faciobraquial y afasia de expresión de instauración aguda 8 días después de la administración intratecal de metotrexato. Luego de excluir otras patologías más frecuentes de origen vascular y la evolución típica del cuadro, con resolución espontánea ad integrum de los síntomas, se arribó al diagnóstico de encefalopatía subaguda reversible por metotrexato.

Encefalopatía subaguda reversible por metotrexato: notificación de un caso pediátrico / Methotrexate-induced stroke-like syndrome: A pediatric case report

Las leucemias son las neoplasias malignas más frecuentes en la infancia; la leucemia linfoblástica aguda (LLA) es la más frecuente. Desde principios de los 80, la adición de metotrexato intratecal a los esquemas de quimioterapia ha sido beneficiosa para prevenir la recidiva en el sistema nervioso central y evitar el uso de radioterapia. Su mecanismo de acción es la inhibición de la enzima dihidrofolato reductasa, por lo que posee múltiples efectos adversos (neurotoxicidad aguda, subaguda o crónica) después de la infusión intratecal o de dosis altas por vía intravenosa.Se presenta un paciente de 11 años con diagnóstico de LLA de línea T (LLA-T), que presenta hemiparesia faciobraquial y afasia de expresión de instauración aguda 8 días después de la administración intratecal de metotrexato. Luego de excluir otras patologías más frecuentes de origen vascular y la evolución típica del cuadro, con resolución espontánea ad integrum de los síntomas, se arribó al diagnóstico de encefalopatía subaguda reversible por metotrexato.

Leukemias are the most frequent malignant neoplasms in childhood; acute lymphoblastic leukemia (ALL) is the most frequent. The addition of intrathecal methotrexate to chemotherapy regimens has been beneficial in preventing relapse to the central nervous system and avoiding the use of radiation therapy. Due to its mechanism of action, by inhibiting the enzyme dihydrofolate reductase, when it is used systemically, it has multiple expected adverse effects such as mucositis, myelosuppression and it has also been observed after intrathecal administration or high intravenous doses, acute, subacute neurotoxicity where stroke like syndrome is found. We present an 11-year-old patient diagnosed with T-ALL, who manifested after 8 days of intrathecal administration of methotrexate, faciobrachial hemiparesis and acute onset expression aphasia. The diagnosis of subacute encephalopathy reversible by methotrexate was reached by excluding other more frequent pathologies and the typical evolution, with spontaneously ad integrum resolution of the symptoms

Efficacy and safety of combined administration of erythropoietin and iron in comparison to iron therapy alone in orthopaedic surgery: systematic review and metanalysis.

INTRODUCTION: Iron deficiency anaemia in orthopaedic surgery is common and there is increased risk of blood transfusion and associated adverse reactions. The management involves administration of iron (oral or intravenous) and erythropoietin stimulating agents. MATERIAL AND METHODS: We searched for PubMed, Embase, Google Scholar and Cochrane database to identify the studies from inception to April 2021. Randomized controlled trials with adult patients undergoing orthopedic surgery were included. The metanalysis compared patients who were administered combination of erythropoietin stimulating agents and iron in one group and iron alone. The primary outcome was the rate of blood transfusion and the secondary outcome studied were postoperative hemoglobin concentration, after treatment hemoglobin levels, and complications like mortality, stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism and renal dysfunction. RESULTS: Eleven studies were included. The combination of ESA and iron decreased number of patients who required blood transfusion in comparison to patients treated with iron therapy alone (RR, 0.73; 95% CI, 0.59 to 0.91, I. CONCLUSION: 2 = 65%; p = 0.005). In subgroup analysis with oral and intravenous iron, the difference was not statistically significant (p = 0.24). Administration of erythropoietin either in high ( 80,000 IU) or low dose ( 80,000 IU) resulted in lower blood transfusion rates (p = 0.0007) with no significant difference between groups. The risk of mortality, myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism did not significantly increase. Combined administration of ESA and iron versus iron only reduces the number of red blood cell transfusions in the postoperative period in orthopedic procedures with minimal risk of complications.

INTRODUCCIÓN: La anemia por deficiencia de hierro en la cirugía ortopédica es común y existe un mayor riesgo de transfusión de sangre y reacciones adversas asociadas. El tratamiento implica la administración de hierro (oral o intravenoso) y agentes estimulantes de la eritropoyetina. MATERIAL Y MÉTODOS: Se realizaron búsquedas en PubMed, Embase, Google Académico y la base de datos Cochrane para identificar los estudios desde su inicio hasta Abril de 2021. Se incluyeron ensayos controlados aleatorios con pacientes adultos sometidos a cirugía ortopédica. El metaanálisis comparó pacientes a los que se les administró una combinación de agentes estimulantes de la eritropoyetina y hierro en un grupo y hierro solo. El resultado primario fue la tasa de transfusión de sangre y el resultado secundario estudiado fue la concentración de hemoglobina postoperatoria, los niveles de hemoglobina después del tratamiento y complicaciones como mortalidad, accidente cerebrovascular, infarto de miocardio, trombosis venosa profunda, embolia pulmonar y disfunción renal. RESULTADOS: Se incluyeron 11 estudios. La combinación de AEE y hierro disminuyó el número de pacientes que requirieron transfusión de sangre en comparación con los pacientes tratados con tratamiento con hierro solo (RR, 0.73; IC del 95%, 0.59 a 0.91, I. CONCLUSIÓN: 2 = 65%; p = 0.005). En el análisis de subgrupos con hierro oral e intravenoso, la diferencia no fue estadísticamente significativa (p = 0.24). La administración de eritropoyetina en dosis altas ( 80,000 UI) o bajas ( 80,000 UI) dio lugar a tasas de transfusión de sangre más bajas (p = 0.0007) sin diferencias significativas entre los grupos. El riesgo de mortalidad, infarto de miocardio, accidente cerebrovascular, trombosis venosa profunda o embolia pulmonar no aumentó significativamente. La administración combinada de AEE y hierro frente al hierro solo reduce el número de transfusiones de glóbulos rojos en el período postoperatorio en procedimientos ortopédicos con un riesgo mínimo de complicaciones.

Calcium supplementation and cardiovascular disease in postmenopausal women: a study in South Brazil / Suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa: um estudo no Sul do Brasil

Objective: To evaluate the link between calcium supplementa- tion and cardiovascular disease in postmenopausal women (aged 55 years or older). Methods: A standardized questionnaire was employed to collect data about calcium supplements, eart di- sease, and demographic of women attended at Primary Care in the South Region of Brazil. Generalized linear regression models were performed to evaluate the association and adjust for poten- tial confounders. Results: Overall, 1,057 women completed the questionnaire. Information about calcium supplementation was present in 1,035 questionnaires. The mean ± standard deviation of the age of participants was 67.2±7.6 years. The frequency of calcium supplementation was 18.6%. There was no association between heart failure, stroke, and ischemic heart disease and cal- cium supplementation (prevalence ratio; 95% confidence interval of 0.3; -0.9-0.4, -0.2; -0.8-0.4 and -0.5; -1.0-0.02, respectively. Con- clusions: Our study did not find an association of higher risk of cardiovascular disease in women using calcium supplementation at Primary Care in South Brazil.

Objetivo: Avaliar a ligação entre a suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa (com 55 anos ou mais). Métodos: Um questionário padronizado foi em- pregado para coletar dados sobre suplementos de cálcio, doenças cardíacas e demográficos de mulheres que frequentavam a Aten- ção Primária na Região Sul do Brasil. Modelos de regressão linear generalizada foram realizados para avaliar a associação e ajustar os potenciais fatores de confusão. Resultados: No total, 1.057 mulheres responderam ao questionário. As informações sobre su- plementação de cálcio estavam presentes em 1.035 questionários. A média ± desvio-padrão da idade dos participantes foi de 67,2 ± 7,6 anos. A frequência de suplementação de cálcio foi de 18,6%. Não houve associação entre insuficiência cardíaca, acidente vas- cular cerebral e doença cardíaca isquêmica e suplementação de cálcio (razão de prevalência; intervalo de confiança de 95% de -0,3; -0,9-0,4, -0,2; -0,8-0,4 e -0,5; -1,0-0,02, respectivamente). Con- clusão: Nosso estudo não encontrou associação de maior risco de doença cardiovascular em mulheres em uso de suplementação de cálcio na Atenção Primária no Sul do Brasil.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.

Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke.

The burden of smoking-related diseases in Brazil: mortality, morbidity and costs.

Advances in tobacco control in Brazil can be reflected in the decrease in prevalence over the past two decades. Death statistics and the occurrence of events and direct costs attributable to tobacco-related diseases have not been frequently estimated in the country. The goal of this article is to estimate the burden of smoking in 2011 regarding mortality, morbidity and medical care costs of the main tobacco-related diseases. A probabilistic microsimulation health economic model was built. The model incorporates the natural history, costs and quality of life of all the tobacco-related adult-specific diseases. Smoking was accountable for 147,072 deaths, 2.69 million years of life lost, 157,126 acute myocardial infarctions, 75,663 strokes, and 63,753 cancer diagnoses. The direct cost for the health system was of BRL 23.37 billion. The monitoring of tobacco-related burden is an important strategy to guide decision-makers and to strenghten health public policies.

Estimativa da carga do tabagismo no Brasil: mortalidade, morbidade e custos / Estimación de la carga de enfermedad atribuible al tabaquismo en Brasil: mortalidad, morbilidad y costos / The burden of smoking-related diseases in Brazil: mortality, morbidity and costs

Os avanços no controle do tabagismo no Brasil podem ser verificados na redução da prevalência nas últimas duas décadas. As estatísticas de óbitos, ocorrência de eventos e custos diretos atribuíveis às doenças tabaco-relacionadas não são estimadas com frequência no país. O objetivo deste artigo foi estimar a carga do tabagismo em 2011, em termos de mortalidade, morbidade e custos da assistência médica das principais doenças tabaco-relacionadas. Desenvolveu-se um modelo econômico baseado em uma microssimulação probabilística de milhares de indivíduos através de coortes hipotéticas que considerou a história natural, os custos diretos em saúde e a qualidade de vida desses indivíduos. O tabagismo foi responsável por 147.072 óbitos, 2,69 milhões anos de vida perdidos, 157.126 infartos agudos do miocárdio, 75.663 acidentes vasculares cerebrais e 63.753 diagnósticos de câncer. O custo para o sistema de saúde foi de R$ 23,37 bilhões. O monitoramento da carga do tabagismo é uma importante estratégica para informar aos tomadores de decisão e fortalecer a política pública de saúde.

Los avances en el control del tabaquismo en Brasil pueden reflejarse en la reducción de la prevalencia observada en las últimas dos décadas. Las estadísticas de muertes, incidencia de eventos y costos directos atribuibles a las enfermedades, relacionadas con el tabaquismo, no han sido estimadas frecuentemente en el país. El objetivo de este estudio fue estimar la carga del tabaquismo en el año 2011, en términos de mortalidad, morbilidad y costos de asistencia médica para las patologías relacionadas con el tabaquismo. Se construyó un modelo de microsimulación probabilístico que incorpora la historia natural, los costos y la calidad de vida de los individuos. En 2011, el tabaquismo fue responsable de 147.072 muertes prematuras, 2,69 millones de años de vida perdidos, 157.126 infartos de miocardio, 75.663 accidentes cerebro-vasculares y 63.753 diagnósticos de cáncer. El costo directo fue de R$ 23,37 mil millones. El monitoreo de la carga de enfermedad atribuible al tabaquismo es una importante estrategia para informar a los responsables de las políticas públicas de salud.

Advances in tobacco control in Brazil can be reflected in the decrease in prevalence over the past two decades. Death statistics and the occurrence of events and direct costs attributable to tobacco-related diseases have not been frequently estimated in the country. The goal of this article is to estimate the burden of smoking in 2011 regarding mortality, morbidity and medical care costs of the main tobacco-related diseases. A probabilistic microsimulation health economic model was built. The model incorporates the natural history, costs and quality of life of all the tobacco-related adult-specific diseases. Smoking was accountable for 147,072 deaths, 2.69 million years of life lost, 157,126 acute myocardial infarctions, 75,663 strokes, and 63,753 cancer diagnoses. The direct cost for the health system was of BRL 23.37 billion. The monitoring of tobacco-related burden is an important strategy to guide decision-makers and to strenghten health public policies.

Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials.

OBJECTIVES: Five randomized, phase-3 trials demonstrated the efficacy and safety of conjugated estrogens/bazedoxifene (CE/BZA) in treating menopausal symptoms and preserving bone. This pooled analysis of these studies describes the cardiovascular safety of CE/BZA. METHODS: We pooled cardiovascular adjudicated safety data from healthy, non-hysterectomized, postmenopausal women who received ≥ 1 dose of CE 0.45 mg/BZA 20 mg (n = 1585), CE 0.625 mg/BZA 20 mg (n = 1583), any CE/BZA dose (n = 4868), or placebo (n = 1241) for up to 2 years in five trials. Venous thromboembolic events (VTEs), coronary heart disease (CHD), and cerebrovascular events were reviewed by three different independent adjudication committees and summarized using a meta-analytic approach. RESULTS: The rate of VTEs per 1000 woman-years (95% confidence interval, CI) was 0.3 (0.0-2.0) in women taking CE 0.45 mg/BZA 20 mg, 0 (0.0-1.5) in those taking CE 0.625 mg/BZA 20 mg, 0.7 (0.0-1.5) among women taking any CE/BZA dose, and 0.6 (0.0-2.9) with placebo. The incidence of stroke per 1000 woman-years (95% CI) was 0.4 (0.0-2.4), 0.2 (0.0-1.9), 0.44 (0.0-1.1), and 0.0 (0.0-1.7), respectively. The CHD rate per 1000 woman-years was 2.6 (0.0-5.6), 1.4 (0.0-3.9), 2.4 (1.00-3.7) and 2.0 (0.0-5.2). Compared with placebo, relative risk (95% CI) with any CE/BZA dose was 0.5 (0.1-1.8) for VTE, 0.5 (0.1-2.6) for stroke, and 0.63 (0.23-1.74) for CHD. CONCLUSIONS: Up to 2 years of CE 0.45 or CE 0.625 mg with BZA 20 mg had an acceptable cardiovascular safety profile, with rates of stroke and CHD comparable to placebo in healthy postmenopausal women. VTE risk was low.

Analysis of antithrombotic therapy in elderly patients with atrial fibrillation.

This study aimed to analyze the impact factors and outcome of antithrombotic therapy in elderly patients over 65 years old that suffered from atrial fibrillation (AF). A total of 256 elderly patients with AF over 65 years old were divided into 3 groups: 65-74 years old (N = 86), 75-84 years old (N = 122), and over 85 years old (N = 48). The clinical characteristics, antithrombotic therapy, and its related impact factors were retrospectively analyzed. Of all patients, 187 received antithrombotic therapy. In the 65-74 year-old group, 78 patients received antiplatelet treatment (90.7%) and 5 patients received anticoagulation treatment (5.8%). In the 75-84 year-old group, 76 patients received antiplatelet treatment (62.3%) and 14 patients received anticoagulation treatment (11.5%). In the group of over 85 year-olds, 33 patients received antiplatelet therapy (68.8%) and 4 patients received anticoagulation treatment (8.3%). Eleven patients had deep vein thrombosis and atrial thrombosis during antiplatelet therapy (5.9%), 5 patients had gastrointestinal hemorrhage after antiplatelet therapy (2.7%), 2 patients had gastrointestinal bleeding, and 3 patients had brain hemorrhage after anticoagulation treatment (21.7%). Suboptimal antithrombotic therapy was observed in the elderly patients with AF, partly owing to the risks of both thromboembolism and bleeding.

Minocycline treatment and bone marrow mononuclear cell transplantation after endothelin-1 induced striatal ischemia.

We explored whether the modulation of microglia activation with minocycline is beneficial to the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted after experimental stroke. Male Wistar adult rats were divided in four experimental groups: ischemic control saline treated (G1, N = 6), ischemic minocycline treated (G2, N = 5), ischemic BMMC treated (G3, N = 5), and ischemic minocycline/BMMC treated (G4, N = 6). There was a significant reduction in the number of ED1+ cells in G3 animals (51.31 ± 2.41, P < 0.05), but this effect was more prominent following concomitant treatment with minocycline (G4 = 29.78 ± 1.56). There was conspicuous neuronal preservation in the brains of G4 animals (87.97 ± 4.27) compared with control group (G1 = 47.61 ± 2.25, P < 0.05). The behavioral tests showed better functional recovery in animals of G2, G3, and G4, compared with G1 and baseline (P < 0.05). The results suggest that a proper modulation of microglia activity may contribute to a more permissive ischemic environment contributing to increased neuroprotection and functional recovery following striatal ischemia.

[Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects]. / Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.

Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais / Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

Os anti-inflamatórios não esteroides (AINEs) encontram-se entre os medicamentos mais prescritos em todo o mundo. Essa classe heterogênea de fármacos inclui a aspirina e vários outros agentes inibidores da ciclo-oxigenase (COX), seletivos ou não. Os AINEs não seletivos são os mais antigos, e designados como tradicionais ou convencionais. Os AINEs seletivos para a COX-2 são designados COXIBEs. Nos últimos anos, tem sido questionada a segurança do uso dos AINEs na prática clínica, particularmente dos inibidores seletivos da COX-2. As evidências sobre o aumento do risco cardiovascular com o uso de AINEs são ainda incompletos, pela ausência de ensaios randomizados e controlados com poder para avaliar desfechos cardiovasculares relevantes. Entretanto, os resultados de estudos clínicos prospectivos e de meta-análises indicam que os inibidores seletivos da COX-2 exercem importantes efeitos cardiovasculares adversos, que incluem aumento do risco de infarto do miocárdio, acidente vascular cerebral, insuficiência cardíaca, insuficiência renal e hipertensão arterial. O risco desses efeitos adversos é maior em pacientes com história prévia de doença cardiovascular ou com alto risco para desenvolvê-la. Nesses pacientes, o uso de inibidores da COX-2 deve ser limitado àqueles para os quais não há alternativa apropriada e, mesmo assim, somente em doses baixas e pelo menor tempo necessário. Embora os efeitos adversos mais frequentes tenham sido relacionados à inibição seletiva da COX-2, a ausência de seletividade para essa isoenzima não elimina completamente o risco de eventos cardiovasculares, de modo que todos os fármacos do largo espectro dos AINEs somente devem ser prescritos após consideração do balanço risco/benefício.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.