Evolução intra-hospitalar e tardia após primeiro infarto agudo do miocárdio: um estudo de mundo real comparando coortes de mulheres e homens no brasil, na rede colaborativa trinetx / In-hospital and late evolution after the first acute myocardial infarction: a real world study comparing cohorts of women and men in brazil, in the trinetx collaborative network

INTRODUÇÃO: Diversos estudos demonstram piores desfechos em mulheres após infarto agudo do miocárdio (IAM) quando comparados ao sexo masculino, mesmo após ajuste para covariáveis. As justificativas para essa desigualdade não são bem esclarecidas. Um fator inegável é a baixa representatividade feminina nos estudos clínicos randomizados e observacionais, e a consequente lacuna no conhecimento sobre as particularidades nessa população. No Brasil, apenas um registro comparou coortes de homens e mulheres após internação por síndrome coronariana aguda, com resultados conflitantes em relação à literatura global, mais extensa e robusta. OBJETIVO: Comparar, com base em dados de mundo real, a ocorrência de eventos cardiovasculares (ECV) entre mulheres e homensinternados por primeiro IAM em hospitais brasileiros. MÉTODOS: Estudo de coorte retrospectivo, com dados extraídos da plataforma global TriNetX, alimentada por prontuários eletrônicos de 13 instituições brasileiras, incluindo pacientes de ambos os sexos com diagnóstico confirmado de IAM pela classificação internacional de doenças (CID) versão 11, código I21. O desfecho primário avaliado foi o composto de óbito, choque cardiogênico (CC), edema agudo pulmonar, e parada cardiorrespiratória (PCR) ressuscitada durante internação hospitalar. Os desfechossecundários avaliados foram óbito, insuficiência cardíaca (ICC), ou hospitalização por novo IAM após 5 anos da alta hospitalar. Resultados plotados em Odds Ratio (OR) com intervalo de confiança (IC) de 95%, e teste de significância em 5%, e curvas de Kaplan-Meier com teste de log-rank para significância (Figura). Análise sobre procedimentos de revascularização miocárdica e ajuste após pareamento por escore de propensão serão apresentados a posteriori. RESULTADOS: O estudo incluiu 11.605 pacientes, com 7.442 homens (64,1%) e 4.163 (35,9%) mulheres. O desfecho primário ocorreu em 439 homens (5,9%) e 307 mulheres (7,4%). O sexo masculino foi associado à menor ocorrência do desfecho primário em relação ao feminino [OR 0,8 (0,68-0,92), p=0.02]. Após 5 anos, 435 homens (5,8%) e 309 mulheres (7,4%) apresentaram ICC [OR 0,77 (0,66-0,90), p=0.001], e 1.007 homens (13,5%) e 520 mulheres (12,5%) apresentaram novo IAM [OR 1,096 (0,98-1,23), p=0.112]. CONCLUSÕES: Nesta coorte brasileira de IAM, o sexo feminino foi associado à maior ocorrência de ECV (óbito, CC, edema agudo pulmonar e PCR ressuscitada) durante internação hospitalar e menor sobrevida livre de ECV após 5 anos do primeiro evento.

Rivaroxabana em Pacientes Ambulatoriais com COVID-19 Leve ou Moderada: Fundamentação e Desenho do Estudo CARE (CARE - Coalition COVID-19 Brazil VIII) / Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII)

Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Abstract Background Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. Objective To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. Methods The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. Results Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Conclusion The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

Justificativa e Desenho do Ensaio Clínico Randomizado COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V): Hidroxicloroquina vs. Placebo em Pacientes Não Hospitalizados / Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients

Resumo Fundamento Apesar da necessidade de opções terapêuticas específicas para a doença do coronavírus 2019 (covid-19), ainda não há evidências da eficácia de tratamentos específicos no contexto ambulatorial. Há poucos estudos randomizados que avaliam a hidroxicloroquina (HCQ) em pacientes não hospitalizados. Esses estudos não indicaram benefício com o uso da HCQ; no entanto, avaliaram desfechos primários diferentes e apresentaram vieses importantes na avaliação dos desfechos. Objetivo Investigar se a HCQ possui o potencial de prevenir hospitalizações por covid-19 quando comparada ao placebo correspondente. Métodos O estudo COVID-19 Outpatient Prevention Evaluation (COPE) é um ensaio clínico randomizado, pragmático, duplo-cego, multicêntrico e controlado por placebo que avalia o uso da HCQ (800 mg no dia 1 e 400 mg do dia 2 ao dia 7) ou placebo correspondente na prevenção de hospitalizações por covid-19 em casos precoces confirmados ou suspeitos de pacientes não hospitalizados. Os critérios de inclusão são adultos (≥ 18 anos) que procuraram atendimento médico com sintomas leves de covid-19, com randomização ≤ 7 dias após o início dos sintomas, sem indicação de hospitalização na triagem do estudo e com pelo menos um fator de risco para complicações (> 65 anos, hipertensão, diabetes melito, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). Todos os testes de hipótese serão bilaterais. Um valor de p < 0,05 será considerado estatisticamente significativo em todas as análises. Clinicaltrials.gov: NCT04466540. Resultados Os desfechos clínicos serão avaliados centralmente por um comitê de eventos clínicos independente cegado para a alocação dos grupos de tratamento. O desfecho primário de eficácia será avaliado de acordo com o princípio da intenção de tratar. Conclusão Este estudo apresenta o potencial de responder de forma confiável a questão científica do uso da HCQ em pacientes ambulatoriais com covid-19. Do nosso conhecimento, este é o maior estudo avaliando o uso de HCQ em indivíduos com covid-19 não hospitalizados.

Abstract Background Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation. Objective To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo. Methods The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value < 0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540. Results Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle. Conclusion This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.

Survival curve identifes critical period for postoperative mortality in cardiac patients undergoing emergency general surgery

The number of non-cardiac major surgeries carried out has signifcantly increased in recent years to around 200 million procedures carried out annually. Approximately 30% of patients submitted to non-cardiac surgery present some form of cardiovascular comorbidity. In emergency situations, with less surgery planning time and greater clinical severity, the risks become even more signifcant. The aim of this study is to determine the incidence and clinical outcomes in patients with cardiovascular disease submitted to non-cardiac surgical procedures in a single cardiovascular referral center. This is a prospective cohort study of patients with cardiovascular disease submitted to non-cardiovascular surgery. All procedures were carried out by the same surgeon, between January 2006 and January 2018. 240 patients included were elderly, 154 were male (64%), 8 patients presented two diagnoses. Of the resulting 248 procedures carried out, 230 were emergency (92.8%). From the data obtained it was possible to estimate the day from which the occurrence of mortality is less probable in the postoperative phase. Our research evaluated the epidemiological profle of the surgeries and we were able to estimate the survival and delimit the period of greatest risk of mortality in these patients. The high rate of acute mesenteric ischemia was notable, a serious and frequently fatal condition.

High-density lipoprotein-cholesterol functionality and metabolic syndrome: Protocol for review and meta-analysis

INTRODUCTION: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver. As one of the key functions of HDL, their hypothesis was that if they could measure HDL-C-efflux capacity, they would have a better handle on the role of HDL in atherosclerosis. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between HDL-C functionality and MetS. The aim of this study is to examine this association of HDL-C functionality with MetS in different ages and sex. METHODS AND ANALYSIS: The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar). Studies that examined the association between HDL-C functionality and MetS; focused on cohort, case-control, and cross-sectional studies; were conducted among in adults aged 40 to 70 years; provided sufficient data for calculating odds ratio or relative risk with a 95% confidence interval; were published as original articles written in English or other languages; and have been published until January 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators.

Challenges and Opportunities to Scale Up Cardiovascular Disease Secondary Prevention in Latin America and the Caribbean

Cardiovascular disease (CVD) is the leading cause of death throughout the world; however, a reduction of 21% (age-standardized cardiovascular mortality rates per 100,000 inhabitants) was observed between 1990 and 2010, with more substantial reductions in CVD mortality evident in high-income countries (w42% reduction in CVD deaths).

Epicardial adipose tissue and metabolic syndrome An update protocol for systematic review and meta-analysis

BACKGROUND: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia, and an increased risk of cardiovascular events. However, there are no systematic analyses, or well conducted meta-analyses to evaluate the relationship between epicardial adipose tissue (EAT) and (MetS). The aim of this study is to examine this association of EAT with MetS in different ages and sex. METHODS: The update systematic review, and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that firstly, examined the association between EAT and MetS, secondly, focus on cohort, case-control, and cross-sectional studies, thirdly, were conducted among in adults aged between 40 and 70 years, fourth, provided sufficient data for calculating ORs or relative risk with a 95% CI, fifth, were published as original articles written in English or other languages, and sixth, have been published until January year 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators. RESULTS: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. This study will provide a high quality synthesis on the association of EAT and MetS. CONCLUSION: This systematic review will provide evidence to assess whether there is a strong association of EAT and MetS, and its components.

Statins in adult patients with HIV Protocol for a systematic review and network meta-analysis

BACKGROUND: Patients with HIV have been found to suffer from lipid abnormalities, including elevated levels of total and LDL cholesterol as well as triglyceride levels. Abnormal lipid levels are associated with an increased risk of developing cardiovascular diseases, which are significant causes of mortality among the general population. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of statins classes on HIV patients. METHODS: Randomized clinical trials (RCTs) and observational studies published in English up to 31 December 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross referencing. Dual selection and abstraction of data will occur. The primary outcome will all-cause mortality, new event of acute myocardial infarction, stroke (hemorrhagic and ischemic), hospitalization for acute coronary syndrome and urgent revascularization procedures and cardiovascular mortality. Secondary outcomes will be assessment of the differences in change of total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein (HDL-C). Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of statins that reduce cardiovascular mortality in HIV patients. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. RESULTS AND CONCLUSION: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The evidence will determine which combination of interventions are most promising for current practice and further investigation.

Epicardial adipose tissue and carotid artery disease Protocol for systematic review and meta-analysis

BACKGROUND: Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex. METHODS: This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators. Results: We propose the current protocol to evaluate the evaluation of EAT with ED. CONCLUSION: This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal.

Metabolic syndrome and risk of stroke Protocol for an update systematic review and meta-analysis

INTRODUCTION: The metabolic syndrome is composed of several cardiovascular risk factors and has a high prevalence throughout the world. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between metabolic syndrome and stroke. The aim of this study is to examine this association of metabolic syndrome with stroke in different ages and sex. METHODS AND ANALYSIS: The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar. Studies that examined the association between metabolic syndrome and stroke, had a longitudinal or prospective cohort design, were conducted among in adults aged 40 to 70 years, provided sufficient data for calculating ORs or relative risk with a 95% CI, were published as original articles written in English or other languages, and have been published until December 2017 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators.

Independent predictors of effective blood pressure control in patients with hypertension on drug treatment in Brazil

Population assessment of effective blood pressure (BP) control is fundamental for reducing the global burden of hypertension, especially in low- and middle-income countries. The authors evaluated the effectiveness of BP control and determined independent predictors associated with effective control among patients with hypertension on drug treatment in a large cross-sectional study performed in two metropolitan areas in Brazil's southeast region. A total of 43 647 patients taking antihypertensive treatment were identified. Less than half of the patients (40.9%) had controlled BP (systolic BP <140 mm Hg and diastolic BP <90 mm Hg). Independent predictors of BP control were age, eating fruit daily, physical activity, previous cardiovascular disease, male sex, diabetes mellitus, ethnicity, and obesity. Simple variables associated with BP control may be utilized for knowledge translation strategies aiming to reduce the burden of hypertension...

Secondary CV Prevention in South America in a community setting: the PURE study

BACKGROUND: Despite the availability of evidence-based therapies, there is no information on the use of medications for the secondary prevention of cardiovascular disease in urban and rural community settings in South America. OBJECTIVES: This study sought to assess the use, and its predictors, of effective secondary prevention therapies in individuals with a history of coronary heart disease (CHD) or stroke.METHODS: In the PURE (Prospective Urban Rural Epidemiological) study, we enrolled 24,713 individuals from South America ages 35 to 70 years from 97 rural and urban communities in Argentina, Brazil, Chile, and Colombia. We assessed the use of proven therapies with standardized questionnaires. We report estimates of drug use at national, community, and individual levels and the independent predictors of their utilization through a multivariable analysis model. RESULTS:Of 24,713 individuals, 910 had a self-reported CHD event (at a median of 5 years earlier) and 407 had stroke (6 years earlier). The proportions of individuals with CHD who received antiplatelet medications (30.1%), beta-blockers (34.2%), angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers (36.0%), or statins (18.0%) were low; with even lower proportions among stroke patients (antiplatelets 24.3%, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 37.6%, statins 9.8%). A substantial proportion of patients did not receive any proven therapy (CHD 31%, stroke 54%). A minority of patients received either all 4 (4.1%) or 3 proven therapies (3.3%). Male sex, age >60 years, better education, more wealth, urban location, diabetes, and obesity were associated with higher rates of medication use. In a multivariable model, markers of wealth had the largest impact in secondary prevention...