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Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention.At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy.The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention.Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients’ associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients’ associations – invert the pyramid order.In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden. Resumo: A doença aterosclerótica cardiovascular (DACV) mantém-se a maior causa de morte prematura e de incapacidade, sendo uma prevenção eficaz de risco cardiovascular (CV) fundamental. O WHF Cholesterol Roadmap fornece enquadramento para o desenvolvimento de políticas nacionais, tendo como objetivo a prevenção de DACV. A convite da WHF, um grupo de peritos da Sociedade Portuguesa de Cardiologia (SPC) avaliou a carga do colesterol a nível nacional e discutiu possíveis estratégias para um Roadmap português.A revisão da literatura mostrou uma carga elevada de colesterol em Portugal, sobretudo em pessoas de alto risco CV. Uma infografia, Scorecard, foi construída pela WHF, para mostrar claramente o risco CV e o peso do colesterol em Portugal, sendo útil para advocacia em políticas de saúde.A discussão de peritos e proposta das estratégias preventivas seguiram os cinco pilares do documento da WHF: Melhoria da consciencialização; Abordagens do risco CV e do colesterol nas populações; Avaliação de risco/screening das populações; abordagens a nível do sistema; Seguimento do colesterol e complicações da DACV.Várias recomendações chave foram definidas: incluir todos os stakeholders em programa multidisciplinar nacional; criar plano de atividades estruturadas para aumentar a consciencialização da população; aumentar qualidade da educação contínua em saúde CV; aumentar interação entre profissionais de saúde e outros profissionais; aumentar referenciação de doentes para reabilitação cardiovascular; avaliar níveis de colesterol na população geral, especialmente em alto risco; promover autocuidado dos doentes, envolvendo associações de doentes; usar redes sociais específicas para disseminar informação; criar base nacional de níveis de colesterol com registo sistemático de eventos CV; redefinir estratégias baseadas na avaliação de resultados; criar e envolver mais doentes em associações – inverter a ordem da pirâmide!Em conclusão, a DACV e o peso de colesterol permanecem uma questão global forte em Portugal, necessitando o envolvimento de múltiplos stakeholders na prevenção. O Roadmap de colesterol português pode fornecer algumas soluções para urgentemente mitigar o problema. Abordagens a nível das populações para melhorar a consciencialização e avaliar o risco CV, seguimento do colesterol e das complicações de DACV são fatores chave nesta mudança. Uma call to action é claramente necessária para combater a carga da hipercolesterolemia e DACV.

Aims: Infective endocarditis (IE) is a serious heart valvular condition. While mitral valve prolapse (MVP) has been associated with an increased risk of IE, the magnitude of this association remains poorly quantified. This systematic review aimed to better estimate the risk of developing IE among MVP patients compared with the general population. Methods: MEDLINE, Cochrane Library (CENTRAL) and Web of Science databases were searched electronically to find all the relevant cohort and case-control studies. Pooled estimates of odds ratios (ORs) and 95 % confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. Results: A total of six studies were considered eligible, and the obtained results showed that MVP patients had a higher risk of IE when compared to the general population (OR 7.83, 95 % CI 5.11, 12.02; I2 = 0 %). Posterior analysis according to the risk of bias and study design didn't show any significant variations in the direction and magnitude of the effect. Conclusion: The magnitude of increased risk of IE of 7-fold warrants further attention for patients with MVP. Further contemporary studies and prophylaxis studies should be considered.

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COVID-19 infection is associated with significant complications affecting multiple organs other than the respiratory system. In fact, there seems to be a bidirectional relation between cardiovascular disease and viral infection, as patients with prior cardiac comorbidities are at a higher risk of adverse events during infection, and COVID-19 infection seems to exponentiate the risk of acute and long-term cardiac events. In this review, the authors will discuss the acute and long-term impact of COVID-19 infection in arterial hypertension, heart failure, angina pectoris, myocardial infarction, and atrial fibrillation.

Abstract Respiratory disease and atrial fibrillation (AF) frequent coexist, but the risk of AF among asthma patients is less characterized. Growing evidence suggest that AF shares with asthma a systemic inflammation background and asthma treatments, such as beta agonists, have been associated with increased risk of cardiac arrhythmias. The aim of this systematic review was to assess the risk of AF in patients with asthma in observational studies. We search for longitudinal studies reporting AF outcome in asthma and control patients through MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. The risk of bias of individual studies was evaluated using the ROBINS-E tool. The study protocol was registered at PROSPERO: CRD42020215707. Seven cohort/nested case–control studies with 1 405 508 individuals were included. The mean follow-up time was 9 years, ranging from 1 to 15 years. Asthma was associated with a higher risk of AF (OR 1.15. 95% CI 1.01–1.29). High heterogeneity (I2 = 81%) and overall “serious” risk of bias, lead to a very low confidence in in this result. Asthma was associated with an increased risk of AF. However, the high risk of bias and high heterogeneity reduces the robustness of these results, calling for further high-quality data.

Global warming is a result of the increased emission of greenhouse gases. The consequences of this climate change threaten society, biodiversity, food and resource availability. The consequences include an increased risk of cardiovascular (CV) disease and cardiovascular mortality.In this position paper, we summarize the data from the main studies that assess the risks of a temperature increase or heat waves in CV events (CV mortality, myocardial infarction, heart failure, stroke, and CV hospitalizations), as well as the data concerning air pollution as an enhancer of temperature-related CV risks. The data currently support global warming/heat waves (extreme temperatures) as cardiovascular threats. Achieving neutrality in emissions to prevent global warming is essential and it is likely to have an effect in the global health, including the cardiovascular health. Simultaneously, urgent steps are required to adapt the society and individuals to this new climatic context that is potentially harmful for cardiovascular health. Multidisciplinary teams should plan and intervene healthcare related to temperature changes and heat waves and advocate for a change in environmental health policy. Resumo: O aquecimento global é uma das consequências do aumento da emissão de gases com efeito de estufa. Essa consequência das alterações climáticas é uma ameaça à sociedade, à biodiversidade e à disponibilidade de recursos e alimentos. As consequências para a saúde do aquecimento global incluem o aumento do risco de doenças cardiovasculares (CV) e da mortalidade cardiovascular.Neste position paper resumimos os dados dos principais estudos que avaliam o risco do aumento de temperatura ou a exposição a ondas de calor nos eventos CV (mortalidade CV, enfarte do miocárdio, insuficiência cardíaca, acidente vascular cerebral e hospitalizações CV), assim como os dados relativos à poluição do ar como um potenciador dos riscos de eventos CV relacionados com o aumento da temperatura. Os dados atualmente disponíveis confirmam que o aquecimento global e as ondas de calor (temperaturas extremas) são ameaças cardiovasculares. Nesse contexto, a neutralidade nas emissões deve ser um objectivo prioritário, de modo a reduzir o aquecimento global e, desse modo, reduzir o seu impacto na saúde global, inclusive a saúde cardiovascular. Simultaneamente, deverão ser empregues medidas urgentes de adaptação setorial ao novo contexto climático, potencialmente mais nefasto para a saúde cardiovascular. Equipes multidisciplinares devem planear e intervir nos cuidados de saúde relacionados com o calor e discutir as políticas de saúde relacionadas com o ambiente.

Abstract The COVID-19 pandemic has had a significant impact on global public health, with long-term consequences that are still largely unknown. This study aimed to assess the data regarding acute cardiovascular hospital admissions in five European centers before and during the pandemic. A multicenter, multinational observational registry was created, comparing admissions to the emergency departments during a 3-months period in 2020 (during the pandemic) with the corresponding period in 2019 (pre-pandemic). Data on patient demographics, COVID-19 test results, primary diagnosis, comorbidities, heart failure profile, medication use, and laboratory results were collected. A total of 8778 patients were included in the analysis, with 4447 patients in 2019 and 4331 patients in 2020. The results showed significant differences in the distribution of cardiovascular diseases between the two years. The frequency of pulmonary embolism (PE) increased in 2020 compared to 2019, while acute heart failure (AHF) and other cardiovascular diseases decreased. The odds of PE incidence among hospitalized patients in 2020 were 1.316-fold greater than in 2019. The incidence of AHF was 50.83% less likely to be observed in 2020, and the odds for other cardiovascular diseases increased by 17.42% between the 2 years. Regarding acute coronary syndrome (ACS), the distribution of its types differed between 2019 and 2020, with an increase in the odds of ST-segment elevation myocardial infarction (STEMI) in 2020. Stratification based on sex revealed further insights. Among men, the incidence of AHF decreased in 2020, while other cardiovascular diseases increased. In women, only the incidence of STEMI showed a significant increase. When analyzing the influence of SARS-CoV-2 infection, COVID-positive patients had a higher incidence of PE compared to COVID-negative patients. COVID-positive patients with ACS also exhibited symptoms of heart failure more frequently than COVID-negative patients. These findings provide valuable information on the impact of the COVID-19 pandemic on acute cardiovascular hospital admissions. The increased incidence of PE and changes in the distribution of other cardiovascular diseases highlight the importance of monitoring and managing cardiovascular health during and post pandemic period. The differences observed between sexes emphasize the need for further research to understand potential sex-specific effects of COVID-19 on cardiovascular outcomes.

Abstract Background Renal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension. Methods Electronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP. Results A total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and − 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP. Conclusion Despite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect.

The COVID-19 pandemic had profound implications for patients with cardiovascular diseases (CVDs), both in the short- and long-term. In this article, we provide an overview of the effects of the pandemic on individuals with preexisting cardiovascular conditions. In the short term, the severe acute respiratory syndrome coronavirus 2 infection increased the risk of many cardiovascular events. Furthermore, the pandemic has disrupted health-care systems worldwide, leading to constraints in routine care, and limited access to specialized cardiovascular services and procedure. This has resulted in increased morbidity and mortality rates among patients with CVD (coronary artery disease, hypertrophic cardiomyopathy, heart failure (HF), heart transplant recipients, atrial fibrillation, atrial flutter, previous stroke, or previous peripheral artery disease). In the long term, the COVID-19 impact on patients with CVD extends beyond the acute phase of the disease. Studies have highlighted the development of long-term cardiovascular complications in COVID-19 survivors, such as acute coronary syndrome myocarditis, HF, stroke, venous thromboembolism, and arrhythmias, which may lead to a surge of new cases associated with CVD in the postpandemic era. Health-care systems must prioritize cardiovascular care, developing strategies to identify the patients at higher risk and provide the care to minimize the impact of the pandemic on patients with CVD.

Objectives COMMANDER-HF was a randomised trial comparing rivaroxaban 2.5 mg two times a day to placebo, in addition to antiplatelet therapy, in patients hospitalised for worsening heart failure with coronary artery disease and sinus rhythm. Patients with diabetes are at increased risk of cardiovascular events and therefore have more to gain.Methods and results In this post-hoc analysis, we evaluated the efficacy and safety of rivaroxaban in patients with (n=2052) and without diabetes (n=2970). The primary outcome was the composite of cardiovascular death, myocardial infarction (MI) or ischaemic stroke. HRs and 95% CIs with interaction analyses were used to describe event-rates and treatment effects. Patients with diabetes had a higher prevalence of cardiovascular comorbidities (eg, hypertension, obesity) and increased incidence of cardiovascular events. Adjusted HRs for events in people with versus without diabetes were 1.34 (95% CI 1.19 to 1.50) for the primary outcome, 1.21 (95% CI 0.84 to 1.75) for stroke, 1.51 (95% CI 1.14 to 1.99) for MI, 1.17 (95% CI 1.05 to 1.31) for heart failure hospitalisation and 1.06 (95% CI 0.56 to 2.01) for major bleeding. Rivaroxaban had no significant effect on event-rates in patients with and without diabetes (all interaction p values >0.05). Low-dose rivaroxaban was associated with an overall reduction in ischaemic stroke (HR 0.66; 95% CI 0.47 to 0.95), with no apparent subgroup interaction according to diabetes status (p-int=0.93).Conclusions In COMMANDER-HF a diagnosis of diabetes conferred higher rates of cardiovascular events that, with exception of ischaemic stroke, was not substantially reduced by rivaroxaban. Rivaroxaban was associated with reduced risk of ischaemic stroke for patients with and without diabetes.Trial registration number NCT01877915; Post-results.

Background: Antibiotic prophylaxis in bicuspid aortic valve patients is currently a matter of debate. Although it is no longer recommended by international guidelines, some studies indicate a high risk of infective endocarditis. We aim to evaluate the risk of native valve infective endocarditis in bicuspid aortic valve patients and compare to individuals with tricuspid aortic valve. Methods: Study search of longitudinal studies regarding infective endocarditis incidence in bicuspid aortic valve patients (compared with tricuspid aortic valve/overall population) was conducted through OVID in the following electronic databases: MEDLINE, CENTRAL, EMBASE; from inception until October 2020. The outcomes of interest were the incidence rate and relative risk of infective endocarditis. The relative risk and incidence rate (number of cases for each 10 000 persons-year) with their 95 % confidence intervals (95 %CI) were estimated using a random effects model meta-analysis. The study protocol was registered at PROSPERO CRD42020218639. Results: Eight cohort studies were selected, with a total of 5351 bicuspid aortic valve patients. During follow up, 184 bicuspid aortic valve patients presented infective endocarditis, with an incidence rate of 48.13 per 10,000 patients-year (95 %CI 22.24–74.02), and a 12-fold (RR: 12.03, 95 %CI 5.45–26.54) increased risk compared with general population, after adjusted estimates. Conclusions: This systematic review and meta-analysis suggests that bicuspid aortic valve patients have a significant high risk of native valve infective endocarditis. Large prospective high-quality studies are required to estimate more accurately the incidence of infective endocarditis, the relative risk and the potential benefit of antibiotic prophylaxis.

Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais.

Air pollution is one of the main environmental risk factors for health and is linked to cardiovascular diseases, which are the leading cause of mortality worldwide.In this position paper, we discuss the main air pollutants and how they can promote the development of cardiovascular disease or cardiovascular events. We also summarise the main evidence supporting the association between air pollution and cardiovascular events, such as coronary events (acute coronary syndromes/myocardial infarction; chronic coronary syndromes), stroke, heart failure and mortality. Some recommendations are made based on these data and the European Society of Cardiology guidelines on cardiovascular disease prevention, acknowledging that it is important to increase awareness and literacy on this topic in Portugal. Resumo: A poluição do ar é um dos principais fatores de risco ambiental para a saúde e está associada à principal causa de morte em todo o mundo que são as doenças cardiovasculares. Neste position paper discutimos a forma como os principais poluentes atmosféricos podem promover o desenvolvimento de doenças ou eventos cardiovasculares. Também agregámos a melhor evidência que suporta a associação entre poluição do ar e eventos cardiovasculares, como eventos coronários (síndromes coronárias agudas/enfarte do miocárdio; síndromes coronárias crónicas), acidente vascular cerebral, insuficiência cardíaca e o risco de morte. Foram feitas recomendações de acordo com a evidência, os dados nacionais e as orientações da Sociedade Europeia de Cardiologia sobre prevenção de doenças cardiovasculares, reconhecendo que é importante aumentar a sensibilização e literacia sobre este tema em Portugal.

Acute aortic dissections are unpredictable aortic catastrophes. Although significant recent improvements have been accomplished in the treatment and management of aortic dissections, a significant amount is still not fully understood regarding this deadly condition. Comprehension of aortic dissections is especially important due to the impact of the disease, since a lot of patients die before reaching the hospital and a significant number of the ones who do survive the initial event end up dying during follow-up. The epidemiology and disease characteristics of these conditions are still under investigation and not completely clear. In this article we aim to review the current knowledge on the epidemiology and clinical characteristics of aortic dissections.

Introdução: Portugal é o país da Organização para a Cooperação e Desenvolvimento Económico com maior consumo de ansiolíticos, hipnóticos e sedativos, sendo uma proporção significativa constituída por benzodiazepinas ou análogos, associados a efeitos de tolerância e dependência. Por este motivo, em alternativa às benzodiazepinas para tratamento da insónia, algumas publicações identificam outros fármacos com efeito hipnótico, como antidepressivos, anti-histamínicos, antipsicóticos ou anticonvulsivantes. Assim, torna-se necessário compreender a evolução do consumo destes medicamentos, pelo que foi objetivo deste estudo avaliar a evolução da dispensa de benzodiazepinas, outros fármacos ansiolíticos, hipnóticos ou sedativos não benzodiazepínicos, fármacos com potencial uso off-label na insónia e os resultados de indicadores dos Cuidados de Saúde Primários neste âmbito na região de Lisboa e Vale do Tejo. Material e Métodos: Realizou-se um estudo em base de dados, censitário e retrospetivo, no período de 2013 até 2020, avaliando-se a evolução das variáveis total de doses diárias definidas, doses diárias definidas por 1000 habitantes por dia (DHD) e dos indicadores relevantes. Os dados foram extraídos da plataforma SIARS da Administração Regional de Saúde de Lisboa e Vale do Tejo. Resultados: Verificou-se uma diminuição da dispensa de benzodiazepinas (de 57,44 para 51,77 DHD) mas o aumento da dispensa de não benzodiazepinas e de fármacos com potencial uso off-label (de 6,56 para 8,56 DHD e de 14,70 para 25,92 DHD, respetivamente). O zolpidem foi o mais dispensado entre os fármacos não benzodiazepínicos, acompanhando a tendência crescente de dispensa (de 4,86 para 6,96 DHD). Do conjunto de fármacos com potencial para uso off-label verificaram-se aumentos da dispensa para a trazodona (de 3,81 para 7,92 DHD), mirtazapina (de 3,52 para 6,48 DHD), pregabalina (de 3,15 para 4,87 DHD), quetiapina (de 2,68 para 4,59 DHD) e gabapentina (de 1,32 para 1,90 DHD), mas mais significativo ou apenas verificado nas formulações com dosagem mais baixa. A mediana dos resultados do indicador “proporção de idosos sem prescrição de sedativos, ansiolíticos e hipnóticos” em 2015 foi de 81,0, tendo em 2020 aumentado para 84,9. A mediana do indicador “proporção de utentes sem prescrição prolongada de ansiolíticos, sedativos e hipnóticos” em 2019 foi de 93,6 e aumentou para 94,3 em 2020. Conclusão: Globalmente, verificou-se uma redução da dispensa de benzodiazepinas prescritas na Região de Lisboa e Vale do Tejo. Parece existir uma alteração do padrão de prescrição no tratamento da insónia. São necessários estudos mais robustos para confirmar esta observação.

INTRODUCTION: Out of Hospital Cardiac Arrest (OHCA) is one of the main causes of death worldwide. Most of the intrinsic causes of OHCA tend to be of cardiac origin, however, non-cardiac etiologies such as acute aortic dissection (AAD) may be more common than previously thought. The aim of this focused review is to summarize current knowledge on the association between OHCA and AAD. METHODS: A systematic review was previously performed on the incidence of AAD in the context of OHCA. For this publication, the selected references were reviewed to address three pre-determined questions: 1) How prevalent is Acute Aortic Dissection in Patients presenting with Out of Hospital Cardiac Arrest? 2) What clinical signs are associated with OHCA due to Acute Aortic Dissection? 3) How can we treat these patients and what is their prognosis? RESULTS: AAD may cause OHCA due to several reasons, such as retrograde involvement of the coronary arteries, aortic valve insufficiency, pericardium tamponade, aortic rupture, massive stroke, visceral malperfusion or hypertensive induced heart failure, for example. Since both the treatment and diagnosis of acute aortic dissections have improved, a growing number of OHCA due to AAD patients have been diagnosed and managed, however, the epidemiology and outcomes of these patients are still not fully understood.

Abstract Background Some patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs). Purpose To determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis. Methods In April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents. Results 16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2–11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI − 1.10 to − 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24–71%; I2 = 96%) and 25% (95% CI 20–29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ). Conclusion Sham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.

Abstract Introduction Over the last years, the number of systematic reviews published is steadily increasing due to the global interest in this type of evidence synthesis. However, little is known about the characteristics of this research published in Portuguese medical journals. This study aims to evaluate the publication trends and overall quality of these systematic reviews. Material and methods This was a methodological study. We aimed the most visible Portuguese medical journals indexed in MEDLINE. Systematic reviews were identified through an electronic search (through PUBMED). We included systematic reviews published up to August 2020. Systematic reviews selection and data extraction were done independently by three authors. The overall quality critical appraisal using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) was independently assessed by three authors. Disagreements were solved by consensus. Results Sixty-six systematic reviews published in 5 Portuguese medical journals were included. Most (n = 53; 80.3%) were systematic reviews without meta-analysis. Up to 2010 there was a steady increase in the number of systematic reviews published, followed by a period of great variability of publication, ranging from 1 to 10 in a given year. According to the systematic reviews’ typology, most have been predominantly conducted to assess the effectiveness/efficacy of health interventions (n = 27; 40.9%). General and Internal Medicine (n = 20; 30.3%) was the most addressed field. Most systematic reviews (n = 46; 69.7%) were rated as being of “critically low-quality”. Conclusions There were consistent flaws in the methodological quality report of the systematic reviews included, particularly in establishing a prior protocol and not assessing the potential impact of the risk of bias on the results. Through the years, the number of systematic reviews published increased, yet their quality is suboptimal. There is a need to improve the reporting of systematic reviews in Portuguese medical journals, which can be achieved by better adherence to quality checklists/tools.

Abstract Introduction The summary of product characteristics of vaccines administered intramuscularly, including the vaccine for coronavirus SARS-CoV-2 (COVID-19) and Influenza, warned for risks of bleeding in patients treated with oral anticoagulants. We aimed to estimate the incidence of major bleeding events in this setting and to compare these risks against other vaccination routes. Methods This systematic review included all prospective and retrospective studies enrolling anticoagulated patients that received intramuscular vaccination, published until December 2020 in CENTRAL, MEDLINE and EMBASE. The outcomes of interest were major bleeding and haematoma related with vaccination. The incidence of the outcomes was estimated through a random-effects meta-analysis using the Freeman-Turkey transformation. The results are expressed in percentages, with 95%-confidence intervals (95%CI), limited between 0 and 100%. When studies compared intramuscular vaccination vs. other route, the data were compared and pooled using random-effects meta-analysis. Risk ratios (RR) with 95%CI were reported. Results Overall 16 studies with 642 patients were included. No major bleeding event was reported. The pooled incidence of haematomas following vaccination (mostly against Influenza) in patients treated with oral anticoagulants (mostly warfarin; no data with DOACs / NOACs) was 0.46% (95%CI 0-1.53%). Three studies evaluated the intramuscular vs. subcutaneous route of vaccination. Intramuscular vaccines did not increase the risk of haematoma (RR 0.53, 95%CI 0.10-2.82) compared with subcutaneous route. Conclusions Intramuscular vaccination in anticoagulated patients is safe with very low incidence of haematomas and the best available evidence suggests that using the intramuscular route does not increase the risk of haematomas compared with the subcutaneous route.

Introduction: The cardiovascular risk of Parkinson’s Disease (PD) patients is uncertain. Blood pressure variability (BPV) has been associated with cardiovascular and mortality outcomes. We aimed to evaluate blood pressure variability, as a marker of cardiovascular risk, in patients with PD and matched community controls. Methods: Cross-sectional case-control study was performed. All subjects included in the analysis were clinically evaluated and performed a 24 h ambulatory blood pressure monitoring. BPV was assessed using standard deviations (SDs) of the systolic blood pressure (SBP) and diastolic blood pressure (DBP) for each period – 24 h, daytime, and night-time. Results: The study included 204 participants, 102 in each group. Mean age 66 years old and 59% man. Most PD patients presented mild symptoms (mean Hoehn&Yahr 2.04). Daytime BPV was significantly higher in PD patients (SD SBP 14.1 mmHg vs 12.96 mmHg and SD DBP 9.39 mmHg vs 8.29 mmHg), but 24 h and night-time BPV were non-significantly increased. PD patients present non-significant higher night-time SBP (114 mmHg vs 110 mmHg) as well as higher frequency of non-dippers or reverse dippers BP profiles (51% vs 36%). Conclusion: Our exploratory study suggests that PD patients may present a higher blood pressure variability, which may translate in an increased cardiovascular risk. However, further studies are needed to confirm this hypothesis and causality.

Abstract Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e−4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases. Trial registration: NCT04370808.

Introduction: Pulmonary embolism (PE) patients at low risk of early complications may be considered for early discharge or home treatment. Last decades evidence has been growing about the safety of several clinical prediction rules for selecting those patients, such as simplified Pulmonary Embolism Severity Index (sPESI) and Hestia Criteria. The aim of this review was to compare the safety of both strategies regarding 30-days mortality, venous thromboembolism recurrence and major bleeding. Methods: A systematic literature search was conducted using MEDLINE, CENTRAL and Web of Science on 6th January 2022. We searched for studies that applied both Hestia Criteria and sPESI to the same population. Sensitivity, specificity and diagnostic odds ratio were calculated for both stratification rules. Both Hestia and sPESI criteria of low risk were evaluated to set the number of patients that could be misclassified for each 1000 patients with PE. The estimates were reported with their 95% confidence intervals (95%CI). Results: This systematic review included 3 studies. Only mortality data was able to be pooled. Regarding mortality, the sensitivity, specificity and diagnostic odds ratio was 0.923 (95%CI: 0.843-0.964), 0.338 (95%CI: 0.262-0.423) and 6.120 (95%CI: 2.905-12.890) for Hestia Criteria; and 0.972 (95%CI: 0.917-0.991), 0.269 (95%CI: 0.209-0.338) and 12.738 (95%CI: 3.979-40.774) for sPESI score. The negative predictive values were higher than 0.977. The risk of misclassification of high-risk patients in low risk was 5 (95%CI: 3-11) with Hestia and 2 (95%CI: 1-6) with sPESI, for each 1000 patients with PE in terms of mortality. Conclusion: The risk of misclassification of patients presenting with low-risk pulmonary embolism with the intent of early discharge or home treatment with both Hestia Criteria and sPESI score is low and these data support methods for this purpose.

Resumo: Introdução e objetivos: As doenças cardiovasculares são a principal causa de morte em Portugal, sendo a aterosclerose o processo fisiopatológico subjacente mais comum. O objetivo deste estudo foi quantificar o impacto económico da aterosclerose em Portugal através da estimação dos custos associados. Métodos: A estimativa dos custos foi realizada na ótica da prevalência e na perspetiva da sociedade. A prevalência das principais manifestações focais da aterosclerose foi estimada com recurso a três fontes epidemiológicas nacionais. O custo anual da aterosclerose incluiu custos diretos (consumos de recursos) e indiretos (impacto na produtividade da população). Estes custos foram estimados para o ano de 2016 com base nos dados da Base de Dados de Morbilidade Hospitalar, do Sistema de Informação da Administração Regional de Saúde de Lisboa e Vale do Tejo que integra informação da prática clínica real em ambiente de cuidados de saúde primários e do Inquérito Nacional de Saúde de 2014 e na opinião de peritos. Resultados: O custo da aterosclerose em 2016 totalizou cerca de 1,9 mil milhões de euros (58% e 42% correspondendo a custos diretos e indiretos, respetivamente). A maior parte dos custos diretos esteve associada aos cuidados de saúde primários (55%), seguindo‐se o ambulatório hospitalar (27%) e, por último, os episódios de internamento (18%). Os custos indiretos foram principalmente determinados pela não participação no mercado de trabalho (91%). Conclusões: A aterosclerose apresenta um importante impacto económico, correspondendo a uma despesa equivalente a 1% do Produto Interno Bruto nacional e a 11% da despesa corrente em saúde, em 2016. Abstract: Introduction and objectives: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease‐related costs. Methods: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real‐world data from primary care, the 2014 National Health Interview Survey, and expert opinion. Results: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). Conclusions: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.

Objectives: Acute Aortic dissection (AAD) may present as out-of-hospital cardiac arrest (OHCA). However, the incidence of this presentation is not well known. Our aim was to perform a systematic review and meta-analysis of all observational studies reporting on the incidence of AAD in patients with OHCA. Methods: We searched MEDLINE, CENTRAL, PsycInfo, Web of Science Core Collection and OpenGrey databases from inception to March-2021, for observational studies reporting on the incidence of AAD in patients with OHCA. Data was pooled using a random-effects model of proportions. The primary outcome was the incidence of AAD in OHCA patients. Secondary outcomes were the incidence of type A aortic dissections (TAAD) and type B aortic dissections (TBAD) in OHCA patients, overall mortality following AAD-OHCA and risk of death in AAD-OHCA patients compared to risk of death of non-AAD-OHCA patients. Results: Fourteen studies were included. The pooled calculated incidence of OHCA due to AAD was 4.39% (95 %CI: 2.55; 6.8). Incidence of OHCA due to TAAD was 7.18% (95 %CI: 5.61; 8.93) and incidence of OHCA due to TBAD was 0.47% (95 %CI: 0.18; 0.85). Overall mortality following OHCA due to AAD was 100% (95 %CI: 97.62; 100). The risk of death in AAD-OHCA patients compared with non-AAD-OHCA patients was 1.10 (95 %CI: 0.94; 1.30). Conclusion: AAD as a cause of OHCA is more frequent than previously thought. Prognosis is dire, as it is invariably lethal. These findings should lead to a higher awareness of AAD when approaching a patient with OHCA and to future studies on this matter.

Background Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.Objective We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.Methods An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.Results We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA—RR 1.69, 95% CI 1.09 to 2.62, I²—24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.Conclusions Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.Trial registration number CRD42020216178.

Abstract Background: Infective endocarditis (IE) is associated with severe complications and high mortality. The assessment of mortality rates and predictors for fatal events is important to identify modifiable factors related to the pattern of treatment, in order to improve outcomes. Objectives: We sought to evaluate clinical outcomes of patients with IE and to determine predictors of in-hospital mortality. Methods: Retrospective single-center study including patients with IE admitted during a 10-year period (2006-2015). Data on comorbidities, clinical presentation, microbiology and clinical outcomes during hospitalization were evaluated. Risk factors of in-hospital death were analyzed. A p-value < 0.05 was considered significant. Results: A total of 134 cases were included (73% males, mean age of 61 ± 16 years-old). Half of them had previous valvular heart disease. Healthcare-associated IE and negative blood-cultures occurred in 22% and prosthetic IE in 25%. The aortic valve was the one most often affected by infection. Staphylococcus aureus was the most commonly isolated microorganism. Forty-four (32.8%) patients underwent cardiac surgery. The in-hospital mortality rate was 31.3% (42 patients). The identified risk factors for in-hospital mortality were Staphylococcus aureus etiology (OR 6.47; 95% CI: 1.07-39.01; p = 0.042), negative blood-cultures (OR 9.14; 95% CI: 1.42-58.77; p = 0.02), evidence of valve obstruction in echocardiography (OR 8.57; 95% CI: 1.11-66.25; p = 0.039), clinical evolution with heart failure (OR 4.98; 95%CI: 1.31-18.92; p = 0.018) or septic shock (OR 20.26; 95% CI: 4.04-101.74; p < 0.001). Cardiac surgery was a protective factor of mortality (OR 0.14; 95% CI 0.03-0.65; p = 0.012). Conclusion: The risk factors for in-hospital mortality were clinical (heart failure, septic shock), evidence of valve obstruction in echocardiography, Staphylococcus aureus etiology or negative blood cultures. Invasive treatment by surgery significantly decreased the mortality risk.

Introduction: The standard of care for acute ST-elevation myocardial infarction (STEMI) includes the activation of a STEMI care network, the administration of adjuvant medical therapy, and reperfusion through primary percutaneous coronary intervention (PCI). While primary PCI is nowadays the first option for the treatment of patients with STEMI, antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize their clinical outcomes. Objective: The aim of this study was to describe contemporaneous real-world patterns of use of antithrombotic treatments in Portugal for STEMI patients undergoing primary PCI. Methods: An observational, retrospective cross-sectional study was performed for the year 2016, based on data from two national registries: the Portuguese Registry on Acute Coronary Syndromes (ProACS) and the Portuguese Registry on Interventional Cardiology (PRIC). Data on oral antiplatelet and procedural intravenous antithrombotic drugs were retrieved. Results: In 2016, the ProACS enrolled 534 STEMI patients treated with primary PCI, while the PRIC registry reported data on 2625 STEMI patients. Of these, 99.6% were treated with aspirin and 75.6% with dual antiplatelet therapy (mostly clopidogrel). GP IIb/IIIa inhibitors (mostly abciximab) were used in 11.6% of cases. Heparins were used in 80% of cases (78% unfractionated heparin [UFH] and 2% low molecular weight heparin). None of the patients included in the registry were treated with cangrelor, prasugrel or bivalirudin. Missing data are one of the main limitations of the registries. Conclusions: In 2016, according to data from these national registries, almost all patients with STEMI were treated with aspirin and 76% with dual antiplatelet agents, mostly clopidogrel. GP IIb/IIIa inhibitors were used in few patients, and UFH was the most prevalent parenteral anticoagulant drug. Resumo: Introdução: O tratamento do enfarte agudo do miocárdio com elevação do segment ST (EAMCSST) baseia-se na ativação da via verde coronária, na administração de terapêutica médica adjuvante e na reperfusão através de angioplastia primária percutânea. A angioplastia primária constitui o tratamento de primeira linha para o EAMCSST e a terapêutica antitrombótica, incluindo antiagregantes e anticoagulantes, a base do tratamento farmacológico, contribuindo para a melhoria do prognóstico. Objetivo: Descrever dados contemporâneos da vida real da utilização de terapêutica antitrombótica em Portugal, em doentes com EAMCSST submetidos a angioplastia primária. Métodos: Foi realizado um estudo observacional retrospetivo baseado nos dados de dois registos nacionais referentes ao ano de 2016: o Registo Nacional de Síndromes Coronárias Agudas (RNSCA) e o Registo Português de Cardiologia de Intervenção (RPCI). Foram colhidos dados relativos à utilização de antiagregantes plaquetários e terapêutica antitrombótica endovenosa utilizada na angioplastia primária. Resultados: Durante o ano de 2016 foram incluídos 534 doentes no RNSCA e 2625 doentes no RNCI com o diagnóstico de EAMCSST submetidos a angioplastia primária. Aproximadamente 99,6% dos doentes foram tratados com ácido acetilsalicílico (AAS) e 75,6% com terapêutica antiagregante dupla (principalmente clopidogrel). Os inibidores do recetor da GpIIbIIIa foram utilizados em 11,6% das angioplastias primárias (principalmente abxicimab). Relativamente à terapêutica anticoagulante, em 78% dos casos foi utilizada heparina não fracionada (HNF) e em 2% heparina de baixo peso molecular. Nenhum dos doentes incluído no registo foi tratado com cangrelor, prasugrel ou bivalirrudina. Os dados omissos são uma das principais limitações dos registos. Conclusões: Em 2016, de acordo com dados dos registos nacionais, quase todos os doentes foram tratados com AAS e 76% com terapêutica antiagregante dupla, na maioria dos casos incluindo o clopidogrel. Os inibidores dos recetors da GpIIbIIIa foram utilizados num número reduzido de doentes e a HNF foi o principal anticoagulante administrado. Keywords: Myocardial infarction, Antiplatelet, Anticoagulant, Antithrombotic, Adjuvant, Palavras-chave: Enfarte do miocárdio, Antiagregante, Anticoagulante, Antitrombótico, Adjuvante

Randomized controlled trials have yielded conflicting results regarding the impact of beta-blockers on perioperative cardiovascular morbidity and mortality. This Cochrane systematic review assessed the impact of this intervention on mortality and cardiovascular events.Eighty-eight randomized controlled trials with 19 161 participants were included (53 trials on cardiac surgery and 35 trials on non-cardiac surgery).In cardiac surgery perioperative beta-blockers had a protective effect against supraventricular and ventricular arrhythmias but had no significant effect on mortality or on the occurrence of acute myocardial infarction (AMI), stroke, heart failure, hypotension or bradycardia. In non-cardiac surgery, beta-blockers had a protective effect against AMI and arrhythmias, but this was counterbalanced by an increased risk of death and stroke.In conclusion, perioperative use of beta-blockers appears overall to be beneficial in cardiac surgery. However, in non-cardiac surgery the substantial reduction in rhythm disturbances and AMI appears to be offset by an increase in mortality and stroke, and so the systematic use of beta-blockers in this setting is not recommended. Resumo: Os resultados de ensaios clínicos aleatorizados relativos à utilização de betabloqueantes no período perioperatório de cirurgia cardíaca e não cardíaca têm sido controversos. Esta revisão sistemática da Cochrane avaliou o impacto dessa intervenção na mortalidade e eventos cardiovasculares peri-operatórios. Foram incluídos 88 ensaios clínicos aleatorizados com um total de 19 161 participantes (53 ensaios com cirurgia cardíaca e 35 com cirurgia não cardíaca).A utilização perioperatória de betabloqueantes na cirurgia cardíaca reduziu significativamente a ocorrência de disritmias supraventriculares e ventriculares, sem impacto significativo na mortalidade, bem como no risco de enfarte agudo do miocárdio (EAM), acidente vascular cerebral (AVC), insuficiência cardíaca, hipotensão e bradicardia. Por outro lado, na cirurgia não cardíaca, apesar de existir uma redução no risco de EAM e nos eventos arrítmicos supraventriculares, esse efeito foi contrabalançado pelo aumento do risco de morte e AVC.Em conclusão, a utilização de betabloqueantes no período perioperatório de cirurgia cardíaca parece ser benéfica. Por outro lado, na cirurgia não cardíaca apesar da redução significativa de EAM e disritmias, há um aumento da mortalidade e de AVC, pelo que a utilização sistemática de betabloqueantes em doentes submetidos a cirurgia não cardíaca não está recomendada. Keywords: Beta-blockers, Surgery, Mortality, Palavras-chave: Betabloqueantes, Cirurgia, Mortalidade

This article reviews the major pharmacologic features of, and clinical evidence on, adjuvant medical therapy in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. These drugs include oral antiplatelets (aspirin and P2Y12 inhibitors such as clopidogrel, prasugrel and ticagrelor), intravenous antiplatelet agents (the P2Y12 inhibitor cangrelor, GP IIb/IIIa inhibitors such as abciximab, eptifibatide and tirofiban), and intravenous anticoagulant agents (unfractionated heparin, low molecular weight heparin and bivalirudin). Resumo: Neste artigo foram analisadas as principais características farmacológicas e a evidência clínica do uso de terapêutica médica adjuvante em doentes com enfarte do miocárdio com supradesnivelamento do segmento ST tratados com angioplastia primária. Esses fármacos incluem antiagregantes orais (ácido acetilsalicílico e inibidores de P2Y12, tais como clopidogrel, prasugrel, ticagrelor), antiagregantes endovenosos (o inibidor P2Y12 cangrelor, inibidores GpIIbIIIa, como o abciximab, eptifibatide e tirofiban) e agentes anticoagulantes de uso endovenoso (heparina não fracionada, heparina de baixo peso molecular e bivalirudina). Keywords: Myocardial infarction, Antiplatelet, Anticoagulant, Antithrombotic, Adjuvant, Palavras-chave: Enfarte do miocárdio, Antiagregante, Anticoagulante, Antitrombótico, Adjuvante

Background: Previous studies suggested that Parkinson's Disease (PD) patients could have an increased risk of atrial fibrillation. However, data supporting this association is not robust. We aimed to compare the potential risk of atrial fibrillation associated with PD in an age and gender matched case-control study, comparing the p-wave indexes from electrocardiograms and clinical risk scores among groups.Methods: A cross-sectional case-control study was performed. All subjects included in the analysis were clinically evaluated and subjected to a 12-lead electrocardiogram. Two blinded independent raters measured the p-wave duration. Subjects were classified as having normal P-wave duration (

Introduction Criticisms have been raised against the sole use of p-value in interpreting results from randomized controlled trials (RCTs). Additional tools have been suggested, like the fragility index (FI), a measure of a trial's robustness/fragility, and derivative measures. The FI is the minimum number of patients who would have to be converted from nonevents to events, in the group with the least events, for a result to lose statistical significance. Objective This study aimed to evaluate RCT supporting European Society of Cardiology (ESC) guidelines regarding antithrombotics, using the FI and FI-related measures. Methods FI, fragility quotient (FQ), and FI minus LTF lost to follow-up (FI − LTF) were calculated for the RCT underpinning recommendations regarding antithrombotic therapy from the updated ESC guidelines. LTF was compared with FI. Results were calculated for the total group of studies, as per guideline and as per recommendation type. Results Overall, 61 studies were included. The median FI was 24.5 (interquartile range [IQR]: 9.0–60.0) and median FQ was 0.0035 (IQR: 0.0019–0.0056). Median FI − LTF was 2.0 (IQR: 0.0–38.0). Twenty (32.8%) of the studies had one primary or main safety outcome with LTF exceeding FI. Peripheral arterial disease guideline and chronic coronary syndrome guideline had the lowest (2.5; IQR: 1.8–3.3) and the highest (48.5; IQR: 23.8–73.0) FI, respectively. Conclusion The median FI suggests robustness of clinical trials evaluating antithrombotic drugs cited in the guidelines, but about one-third of them had LTF larger than FI. This emphasizes the need for assessing trials' robustness when constructing guidelines.

Objective: Animal studies suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) facilitate the inoculation of potentially leading to a higher risk of infection and/or disease severity. We aimed to systematically evaluate the risk of COVID-19 infection and the risk of severe COVID-19 disease associated with previous exposure to (ACEi) and/or ARB). Methods: MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection were searched in June 2020 for controlled studies. Eligible studies were included and random-effects meta-analyses were performed. The estimates were expressed as odds ratios (OR) and 95% confidence intervals (95%CI). Heterogeneity was assessed with I2 test. The confidence in the pooled evidence was appraised using the GRADE framework. Results: Twenty-seven studies were included in the review. ACEi/ARB exposure did not increase the risk of having a positive test for COVID-19 infection (OR 0.99, 95%CI 0.89–1.11; I2 = 36%; 5 studies, GRADE confidence moderate). The exposure to ACEi/ARB did not increase the risk of all-cause mortality among patients with COVID-19 (OR 0.91, 95%CI 0.74–1.11; I2 = 20%; 17 studies; GRADE confidence low) nor severe/critical COVID-19 disease (OR 0.90, 95%CI 0.74–1.11; I2 = 55%; 17 studies; GRADE confidence very low). Exploratory analyses in studies enrolling hypertensive patients showed a association of ACEi/ARB with a significant decrease of mortality risk. Conclusions: ACEi/ARB exposure does not seem to increase the risk of having the SARS-CoV-2 infection or developing severe stages of the disease including mortality. The potential benefits observed in mortality of hypertensive patients reassure safety, but robust studies are required to increase the confidence in the results.

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Background The prevalence of thoracic aortic aneurysms (TAA) in patients with known abdominal aortic aneurysms (AAA) is not well known and understudied. Our aim was to conduct a systematic review and meta‐analysis of the overall prevalence of synchronous and metachronous TAA (SM‐TAA) in patients with a known AAA and to understand the characteristics of this sub‐population. Methods and Results We searched MEDLINE, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to November 2019 for all population‐based studies reporting on the prevalence of SM‐TAAs in a cohort of patients with AAA. Article screening and data extraction were performed by 2 authors and data were pooled using a random‐effects model of proportions using Freeman‐Tukey double arcsine transformation. The main outcome was the prevalence of SM‐TAAs in patients with AAAs. Secondary outcomes were the prevalence of synchronous TAAs, metachronous TAAs, prevalence of TAAs in patients with AAA according to the anatomic location (ascending, arch, and descending) and the differences in prevalence of these aneurysms according to sex and risk factors. Six studies were included. The pooled‐prevalence of SM‐TAA in AAA patients was 19.2% (95% CI, 12.3–27.3). Results revealed that 15.2% (95% CI, 7.1–25.6) of men and 30.7% (95% CI, 25.2–36.5) of women with AAA had an SM‐TAA. Women with AAA had a 2‐fold increased risk of having an SM‐TAA than men (relative risk [RRs], 2.16; 95% CI, 1.32–3.55). Diabetes mellitus was associated with a 43% decreased risk of having SM‐TAA (RRs, 0.57; 95% CI, 0.41–0.80). Conclusions Since a fifth of AAA patients will have an SM‐TAA, routine screening of SM‐TAA and their clinical impact should be more thoroughly studied in patients with known AAA.

Introduction and Aims: Shorter patient delays are associated with a better prognosis for patients diagnosed with ST-segment elevation myocardial infarction (STEMI). This study aimed to identify predictors of patient delay in the Portuguese population. Methods: Data on 994 patients with suspected STEMI of less than 12 hours’ duration and referred for primary percutaneous coronary intervention (pPCI) and admitted to 18 Portuguese interventional cardiology centers were collected for a one-month period every year from 2011 to 2015. Univariate and multivariate linear regression models were used to identify predictors of patient delay. Results: No significant differences were observed in patient delay over the course of the survey. The multivariate analysis identified five predictors of patient delay: age ≥75 years (exp[beta] 1.28; 95% CI 1.10-1.50; p=0.001), symptom onset between 0:00 and 8:00 a.m. (exp[beta] 1.26; 95% CI 1.10-1.45; p=0.001), and attending a primary care unit before first medical contact (exp[beta] 1.75; 95% CI 1.41-2.16; p

Abstract Background We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in ‘real-world’ settings. Methods We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006–2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). Results We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54–1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35–0.98; 3500 patients). Conclusions The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensity-score matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI.

Resumo: Introdução: Nos doentes internados com enfarte agudo do miocárdio sem supradesnivelamento de ST (EAM‐NST), o momento mais apropriado para a realização de coronariografia não está completamente definido, embora esteja estabelecido que, nos doentes de alto risco, se deverá realizar nas primeiras 24 horas. O objetivo deste trabalho é descrever a evolução temporal da utilização de uma estratégia invasiva. Adicionalmente, pretende‐se discutir se haverá benefício em estabelecer sistema organizacional similar àquele que já existe para o enfarte com supra de ST. Métodos: Análise retrospetiva dos doentes admitidos com EAM‐NST, incluídos no Registo Nacional de Síndromas Coronárias Agudas, entre 2002‐2015. Avaliou‐se a percentagem de doentes submetidos a coronariografia e o tempo desde a admissão até à coronariografia, de acordo com o ano da admissão, género e idade, assim como a evolução da mortalidade e do tempo de internamento. Resultados: A análise incluiu 18 639 doentes. Entre 2002‐2015, observou‐se um significativo aumento percentual das coronariografias (52,0 versus 83,6%) e angioplastias (23,3 versus 53,0%), assim como nas coronariografias realizadas nas primeiras 24 horas (21,0 versus 48,1%). A mortalidade intra‐hospitalar diminuiu ao longo do período de análise, particularmente nos doentes com mais de 74 anos (9,5 para 3,7%) e no género masculino. Conclusões: A adoção progressiva da estratégia invasiva, em particular da estratégia invasiva precoce, foi acompanhada temporalmente por uma diminuição da mortalidade. Como metade dos doentes de alto risco continua a realizar a coronariografia tardiamente, considera‐se que o EAM‐NST poderia beneficiar com um sistema organizacional como a iniciativa Stent for Life. Abstract: Introduction: In patients with non‐ST‐elevation myocardial infarction (NSTEMI), the best timing for coronary angiography is not definitely established, although it is recognized that in high‐risk patients it should be performed within the first 24 hours. The aim of this work was to describe the evolution over time of the use of an invasive strategy in the treatment of NSTEMI and in‐hospital mortality. Methods: We performed a retrospective analysis of patients admitted with NSTEMI included in the Portuguese Registry on Acute Coronary Syndromes (ProACS) between 2002 and 2015. The annual proportion of patients undergoing coronary angiography and the time from admission to coronary angiography were assessed, as were changes in mortality and length of stay. Results: A total of 18 639 patients with NSTEMI were included in the ProACS registry between 2002 and 2015. Over this period there were significant increases in the proportion of patients undergoing coronary angiography (from 52.0 to 83.6%) and angioplasty (from 23.3 to 53.0%), as well as in the proportion of patients who underwent coronary angiography within 24 hours of admission (from 21.0 to 48.1%). In‐hospital mortality decreased in those aged over 74 years (from 9.5 to 3.7%) and in males. Conclusions: The progressive adoption of an invasive strategy, particularly an early one (within 24 hours), was accompanied by a reduction in in‐hospital mortality. Since coronary angiography is performed late (> 24 hours) in half of NSTEMI patients, these patients could benefit from initiatives similar to Stent for Life. Palavras‐chave: Enfarte agudo do miocárdio sem supra de ST, Evolução temporal no tratamento, Estratégia invasiva precoce, Mortalidade intra‐hospitalar, Stent for Life, Keywords: Non‐ST‐elevation myocardial infarction, Temporal trends, Early invasive strategy, In‐hospital mortality, Stent for Life

IntroductionIbrutinib is an oral covalent inhibitor of Bruton's tyrosine kinase approved for the treatment of patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma and Waldenstrӧm's macroglobulinemia. Ibrutinib has an increased risk of atrial fibrillation but the mechanism is unknown, and hypertension may play a role in the pathogenesis of this adverse drug reaction.MethodsWe aimed to review the risk of hypertension and atrial fibrillation as adverse events associated with ibrutinib through a systematic review with meta-analysis of randomized controlled trials (RCTs) retrieved in December 2018 on MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov. The data were pooled using random-effects meta-analyses using the risk ratio (RR) with the 95% confidence interval (95%CI). The confidence on the pooled estimates was ascertained through the grading of recommendations assessment, development, and evaluation (GRADE) approach.ResultsThere were 8 eligible RCTs (2580 patients), all reporting safety data of interest. Ibrutinib was associated with a significant increase in the risk of hypertension with a RR of 2.82 (95%CI 1.52-5.23) with moderate quality evidence. Ibrutinib increased significantly the risk of atrial fibrillation with a RR of 4.69 (95%CI 2.17-7.64) with high quality evidence.ConclusionsIbrutinib was associated with significantly increased risks of both hypertension and atrial fibrillation.

Resumo: Introdução e objetivos: Os non‐vitamin K antagonist oral anticoagulants (NOAC) foram recentemente comparticipados para a fibrilhação auricular não‐valvular (FA), sendo relevante determinar o seu custo‐efetividade para a realidade portuguesa. Métodos: Foi especificado um modelo Markov para simular a progressão dos doentes com FA no decurso da sua vida. Os dados de efetividade relativa para os eventos acidente vascular cerebral (isquémico e hemorrágico), hemorragia (intracraniana, outras hemorragias major e hemorragias não‐major clinicamente relevantes), enfarte agudo do miocárdio e descontinuação do tratamento foram obtidos por comparações indiretas entre o apixabano, o dabigatrano e o rivaroxabano (comparador comum: varfarina). As fontes dos dados de consumo de recursos de saúde foram a base de dados dos grupos de diagnóstico homogéneo e painel de peritos. Estimou‐se os anos de vida ganhos, anos de vida ajustados pela qualidade (QALY), custos diretos e rácios de custo‐efetividade incremental (ICER). Resultados: Os anos de vida ganhos e os QALY foram maiores com apixabano, com um ICER versus varfarina e dabigatrano de 5529 €/QALY e 9163 €/QALY, respetivamente. O apixabano foi dominante versus o rivaroxabano (maiores ganhos em saúde e menores custos). Estes resultados foram robustos nas análises de sensibilidade realizadas, tendo o apixabano uma probabilidade de 70% de ser custo‐efetivo (threshold: 20 000 €/QALY) versus o conjunto das restantes opções terapêuticas. Conclusões: A utilização de apixabano em doentes com FA na prática clínica portuguesa é custo‐efetiva versus varfarina e dabigatrano e dominante versus rivaroxabano na perspetiva do SNS. Estas conclusões baseiam‐se em comparações indiretas. Apesar desta limitação, esta informação é relevante para os diferentes decisores em saúde. Abstract: Introduction and Objectives: Recently, three novel non‐vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non‐valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost‐effectiveness of these new oral anticoagulants in Portuguese AF patients. Methods: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non‐major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis‐related groups and an expert panel. Model outputs included life years gained, quality‐adjusted life years (QALYs), direct healthcare costs and incremental cost‐effectiveness ratios (ICERs). Results: Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost‐effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. Conclusions: Apixaban is a cost‐effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision‐makers. Palavras‐chave: Anticoagulantes orais, Fibrilhação auricular, Custo‐efetividade, Anos de vida ajustados pela qualidade, Keywords: Oral anticoagulants, Atrial fibrillation, Cost‐effectiveness, Quality‐adjusted life years

Resumo: Introdução e objetivos: A fibrilhação auricular é a disritmia persistente mais prevalente. Pretendemos estimar a carga e custos da doença atribuíveis à fibrilhação auricular em Portugal com base nas estatísticas demográficas e de saúde. Métodos: Utilizou‐se informação sobre mortalidade por causa da OMS‐Europa. Dados hospitalares foram provenientes da base de dados dos GDH. A carga da doença foi medida pelos DALY (disability‐adjusted life years) ou anos de vida perdidos ajustados por incapacidade, uma métrica adotada pela Organização Mundial de Saúde. Os custos incluíram os consumos de recursos e as perdas de produtividade. A carga e os custos da doença estimados são os atribuíveis à fibrilhação auricular e à sua principal complicação, o acidente vascular cerebral isquémico. Resultados: Em Portugal, no ano 2010, podem atribuir‐se à fibrilhação auricular 4070 mortes correspondendo a 3,8% do total das mortes ocorridas. A carga da doença atribuível à fibrilhação auricular foi estimada em 23.084 DALY: 10.521 decorrentes das mortes prematuras (1,7% dos DALY por morte em Portugal em 2010) e 12 563 devidos à incapacidade gerada pela morbilidade. O total estimado de custos diretos para o sistema de saúde a preços de 2013 atribuíveis à fibrilhação auricular foi de 115 M€ (milhões de euros): 34 M€ em internamento e 81 M€ em ambulatório. Os custos indiretos gerados pela produção perdida devidos à incapacidade causada pela doença foram estimados em 25 M€. Conclusões: A fibrilhação auricular tem um importante impacto social em Portugal devido à mortalidade e morbilidade geradas, podendo‐se‐lhe atribuir em 2013 um custo total de 140 M€, cerca de 0,08% do produto interno bruto. Abstract: Introduction and Objectives: Atrial fibrillation is the most prevalent sustained arrhythmia. This paper estimates the burden and cost of illness attributable to atrial fibrillation in Portugal based on demographic and health statistics. Methods: Mortality data by cause of death came from the European Detailed Mortality Database of the World Health Organization (WHO). Hospital data were taken from the Portuguese diagnosis‐related groups database. The burden of disease was measured using DALYs (disability‐adjusted life years), a metric adopted by the WHO. Costs studied included resource use and lost productivity. The burden and cost of illness are those attributable to atrial fibrillation and its main complication, ischemic stroke. Results: In Portugal, 4070 deaths were attributable to atrial fibrillation in 2010, corresponding to 3.8% of all deaths. In total, the burden of disease attributable to atrial fibrillation was estimated at 23 084 DALYs: 10 521 resulting from premature deaths (1.7% of the total DALYs due to death in 2010 in Portugal), and 12 563 resulting from disability. The total estimated direct costs attributable to atrial fibrillation at 2013 prices were 115 M€ (million euros): 34 M€ for inpatient care and 81 M€ for outpatient care. Indirect costs resulting from lost production due to disability were estimated at 25 M€. Conclusions: Atrial fibrillation has an important social impact in Portugal due to its associated mortality and morbidity, and was responsible in 2013 for a total cost of 140 M€, about 0.08% of gross domestic product. Palavras‐chave: Fibrilhação auricular, Doença cerebrovascular, Custo e carga da doença, Anos de vida perdidos ajustados por incapacidade, Keywords: Atrial fibrillation, Cerebrovascular disease, Cost of illness, Burden of disease, Disability‐adjusted life years

Resumo: A melhoria de parâmetros hemodinâmicos justifica o uso do balão intra‐aórtico (BIA) em doentes com enfarte agudo do miocárdio (EAM) complicado por choque cardiogénico. Esta revisão sistemática da Cochrane avaliou o potencial impacto desta intervenção na mortalidade. Foram avaliados sete ensaios clínicos aleatorizados e controlados com um total de 790 doentes (quatro estudos utilizando a terapêutica médica como comparador e três estudos compararam o BIA com outros dispositivos de assistência ventricular). O uso de BIA não reduziu significativamente a mortalidade a curto ou a longo prazo nos doentes com EAM e choque cardiogénico. Não existe evidência que suporte o seu uso sistemático nestes doentes. Abstract: Improvement of hemodynamic parameters is the rationale for the use of intra‐aortic balloon pump counterpulsation (IABP) in patients with cardiogenic shock following acute myocardial infarction (MI). This Cochrane systematic review evaluated the impact of this intervention in reducing mortality. Seven randomized controlled trials with a total of 790 patients were included (four using medical therapy as a comparator, and three comparing IABP with other ventricular assist devices). IABP did not reduce mortality in either the short or long term. Therefore, the systematic use of IABP in patients with cardiogenic shock following MI cannot be recommended. Palavras‐chave: Choque cardiogénico, Enfarte agudo do miocárdio, Balão intra‐aórtico, Dispositivo de assistência ventricular, Keywords: Cardiogenic shock, Myocardial infarction, Intra‐aortic balloon pump, Left ventricular assist device

Background: Venous thromboembolism (VTE) is a potentially fatal complication of orthopedic surgery, and until recently, few antithrombotic compounds were available for postoperative thromboprophylaxis. The introduction of the non–vitamin K antagonists oral anticoagulants (NOAC), including apixaban, has extended the therapeutic armamentarium in this field. Therefore, estimation of NOAC net clinical benefit in comparison with the established treatment is needed to inform clinical decision making. Objectives: Systematic review to assess the efficacy and safety of apixaban 2.5 mg twice a day versus low-molecular-weight heparins (LMWH) for thromboprophylaxis in patients undergoing knee or hip replacement. Data sources: MEDLINE, Embase, and CENTRAL were searched from inception to September 2016, other systematic reviews, reference lists, and experts were consulted. Study eligibility criteria, participants, and intervention: All major orthopedic surgery randomized controlled trials comparing apixaban 2.5 mg twice daily with LMWH, reporting thrombotic and bleeding events. Data extraction: Two independent reviewers, using a predetermined form. Study appraisal and synthesis methods: The Cochrane tool to assess risk bias was used by two independent authors. RevMan software was used to estimate pooled risk ratio (RR) and 95% confidence intervals (95% CI) using random-effects meta-analysis. Trial sequential analysis (TSA) was performed in statistical significant results to evaluate whether cumulative sample size was powered for the obtained effect. Overall confidence in cumulative evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group methodology. Results: Four studies comparing apixaban 2.5 mg twice daily with LMWH were included, with a total of 11.828 patients (55% undergoing knee and 45% hip replacement). The overall risk of bias across studies was low. In comparison with LMWH (all regimens), apixaban showed a significantly lower risk of VTE events and overall mortality combined (RR: 0.63, 95% CI: 0.42-0.95, I 2 = 84%, n = 8346), but not of major VTE events (RR: 0.62, 95% CI: 0.32-1.19, I 2 = 63%, n = 9493), or of symptomatic VTE events and VTE-related mortality combined (RR: 1.14, 95% CI: 0.68-1.90, I 2 = 0%, n = 11 879). Trial sequential analysis showed that the risk reduction obtained for VTE and mortality was based on underpowered cumulative sample size and effect dimension. Subgroup analysis according to LMWH regimens showed that apixaban reduced the risk of VTE events and overall mortality, and major VTE events, when compared with LMWH once daily, without differences between apixaban and LMWH twice daily. Conclusions: There is low to moderate evidence that in patients undergoing knee or hip replacement, apixaban seems equally effective and safe to LMWH twice a day. When compared with LMWH once a day, apixaban seems a superior thromboprophylaxis option. However, the results are underpowered which precludes definite answers regarding the true net clinical benefit of apixaban versus LMWH in this clinical context.

Resumo: Introdução e objetivo: A anticoagulação oral é uma terapêutica eficaz na prevenção de eventos tromboembólicos, em doentes com fibrilhação auricular (FA). A presente revisão pretendeu estimar a prevalência da terapêutica anticoagulante oral em doentes com FA em Portugal. Métodos: Foi realizada uma pesquisa nas bases de dados MEDLINE, Índex de Revistas Médicas Portuguesas e Catálogo Bibliográfico do Sistema Integrado de Bibliotecas da antiga Universidade Clássica de Lisboa (SIBUL). Estudos observacionais nacionais que reportavam a proporção de doentes anticoagulados com fibrilhação auricular foram incluídos. A estimativa combinada de prevalência de doentes com FA anticoagulados e o respetivo intervalo de confiança 95% (IC95%) foi determinada com recurso a meta‐análise. Resultados: Dos sete estudos incluídos, três estudos foram realizados em ambiente hospitalar e quatro foram realizados na comunidade em geral. Do total de 891 doentes com FA, a estimativa de prevalência de doentes anticoagulados foi de 40% (IC95% 32‐48%). Conclusões: A prevalência de doentes com FA anticoagulados na população estudada é baixa. É necessário promover a mudança dos hábitos de prescrição de anticoagulantes em doentes com FA em Portugal, em concordância com as recomendações internacionais. Abstract: Introduction and Objectives: Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. Methods: MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta‐analysis. Results: Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32–48%). Conclusions: The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Palavras‐chave: Fibrilhação auricular, Anticoagulação, Prevalência, Coumarinicos, Varfarina, Antagonistas da vitamina K, Keywords: Atrial fibrillation, Anticoagulation, Prevalence, Coumarins, Warfarin, Vitamin K antagonists

Resumo: Introdução e objetivos: A não‐adesão à terapêutica constitui um problema de saúde importante. Na Europa, foi estimado que 9% dos eventos cardiovasculares podem ser atribuídos à não‐adesão terapêutica. A complexidade dos esquemas posológicos é um dos fatores apontados como contribuindo para esta problemática. Nesta revisão sistemática pretendemos avaliar o impacto, em doentes com patologia cardiovascular crónica, da frequência posológica na adesão terapêutica. Métodos: Pesquisa na MEDLINE e Cochrane Library (Novembro 2013) de ensaios clínicos controlados e aleatorizados (RCT) que comparassem, em doentes com patologia cardiovascular crónica, diferentes tipos de regimes posológicos (administração única diária versus duas ou mais administrações) e que avaliassem adesão terapêutica. Foram apenas incluídos ensaios com uma duração de pelo menos cinco meses. Os resultados dos estudos foram agregados através de uma meta‐análise (efeitos aleatórios) e calculou‐se o risco relativo (RR) e respetivo intervalo de confiança 95% (IC 95%). A heterogeneidade estatística foi calculada com o teste do I2. Resultados: Foram incluídos quatro RCT (2557 doentes). Os regimes posológicos com administração única diária estão associados a uma redução de 56% do risco de um doente ser não aderente à terapêutica (RR: 0,44; IC 95%: 0,35‐0,54; I2 = 25%). Conclusões: Poucos ensaios clínicos de longo termo avaliaram o impacto da frequência posológica na adesão terapêutica em doentes com patologia cardiovascular crónica. A melhor evidência disponível sugere que a toma de medicamentos em posologia diária única diminui o risco de não‐adesão terapêutica em cerca de 50%. O impacto em termos de outcomes clínicos não está estudado. Abstract: Introduction and Objective: Non‐adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non‐adherence. The complexity of dosing regimens is one of the factors identified as contributing to non‐adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease. Methods: MEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once‐daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow‐up were included. The results of the studies were pooled through a random effects meta‐analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I2 test. Results: Four RCTs (a total of 2557 patients) were included. Dosing regimens with once‐daily administration were associated with a significant 56% reduction in risk of non‐adherence to drug therapy (RR: 0.44; 95% CI: 0.35‐0.54, I2=25%). Conclusions: Few clinical trials have assessed the long‐term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non‐adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established. Palavras‐chave: Adesão medicamentosa, Adesão terapêutica, Compliance do doente, Doenças cardiovasculares, Doença crónica, Posologia de administração diária, Keywords: Medication adherence, Treatment adherence, Patient compliance, Cardiovascular disease, Chronic disease, Drug administration regimen

Resumo: O potencial anti‐inflamatório da colchicina tem vindo a ser avaliado em várias patologias, incluindo a pericardite. A revisão sistemática da Cochrane incluiu quatro ensaios clínicos aleatorizados e controlados, com 564 doentes com pericardite aguda (dois estudos) e pericardite recorrente (dois estudos), seguidos por um período de 20‐24 meses. A colchicina esteve associada a uma redução significativa do risco de persistência de dor torácica (curto prazo) e do risco de recidiva de pericardite (longo prazo), sem aumento significativo dos eventos adversos totais. Apesar da evidência disponível, o uso de colchicina neste contexto mantém‐se off‐label. Abstract: The potential anti‐inflammatory effect of colchicine has been explored in many conditions, including pericarditis. The Cochrane Collaboration Systematic Review included four randomized controlled trials enrolling 564 patients with acute pericarditis (two studies) or recurrent pericarditis (two studies), followed for a period of 20‐24 months. Colchicine was associated with a significant reduction in short‐term persistence of chest pain and in long‐term risk of recurrence of pericarditis. No significant increase in overall adverse events was observed. Despite the available evidence, the use of colchicine in this context remains strictly off‐label. Palavras‐chave: Pericardite, Colchicina, Dor torácica, Keywords: Pericarditis, Colchicine, Chest pain