Abstract The Developmental Origin of Health and Disease (DOHaD) is an area of science dedicated to studying the processes by which insults during critical periods of mammals development leading to physiological changes resultig in diseases throughout life. Studies point to a complex interaction between nutritional status in early life and cardiovascular system homeostasis in which maternal malnutrition during gestation and/or lactation, as well as early weaning, are associated with development of cardiovascular diseases in adulthood. In this context, epigenetic changes, such as DNA methylation, histone acetylation, and change in microRNA expression have been considered molecular bases of cellular plasticity, which can also be gender-dependent. Experimental studies have demonstrated that interventions encompassing the consumption of functional food/bioactive compounds, as well as energetic and nutrients adjustments on the diet, may attenuate or even prevent consequences associated with plasticity of development, improving cardiovascular health. This review aimed to gather and discuss the findings within this context, published over the last ten years.

Resumo Fundamentos: Durante a comercialização de novos medicamentos, efeitos inéditos podem ser descobertos. O dabigratana é um anticoagulante aprovado pela ANVISA em 2008. Objetivos: Avaliar segurança, efetividade, perfil de eventos adversos e adesão terapêutica ao dabigatrana (110 e 150 mg) prescrito para pacientes com fibrilação atrial não valvar. Métodos: Pacientes em uso de dabigatrana foram submetidos a entrevistas ao longo do primeiro ano de tratamento, avaliando-se a prescrição em função da dose, idade, gênero e fatores de risco, bem como a prevalência de eventos adversos e o perfil dos pacientes envolvidos. Resultados: O estudo começou com 139 pacientes havendo redução do número de sujeitos em uso do anticoagulante ao final (10% dose 110 mg e 30% dose 150 mg), sem variação nas proporções dos indivíduos quanto ao gênero (homens≅65%), faixa etária (idade inferior a 75 anos?80%), escores de risco para eventos tromboembólicos (CHA2DS2-VASc≥2 ≅80%) e hemorrágicos (HASBLED<3 ≅50% dose 110mg e ?85% dose 150 mg). O evento adverso mais comum foi a dispepsia (≥10%), independentemente do gênero, porém com menor frequência na faixa etária superior a 75 anos (≅20% dos casos). A dispepsia relacionada ao dabigatrana foi principalmente associada a sua combinação com betabloqueadores (≅70%), porém, minoritariamente com antidiabéticos (≅20%), antiplaquetários (≅10%), inibidores da bomba de prótons (≅30%) e antagonistas de receptores H2 (≅3%). A adesão foi de ≅60%, independentemente dos eventos adversos relatados. Não foram observados casos de evento tromboembólico e nem sangramento maior. Conclusão: O dabigatrana mostrou-se seguro e efetivo nas condições avaliadas

Abstract Background: During its commercialization phase, unprecedented effects of new medicaments can be discovered. Dabigatran is an anticoagulant approved by Brazilian National Health Surveillance Agency in 2008. Objectives: To assess safety, effectiveness adverse event profile and adherence to dabigatran (110 mg and 150 mg) prescribed for patients with non-valvular atrial fibrillation. Methods: Patients taking dabigatran were subjected to interviews during the first year of treatment, evaluating the prescription depending on the dose, age, gender and risk factors as well as the prevalence of adverse events and the profile of the patients involved. Results: Between the beginning and the end of the study there was a reduction in the number of subjects using this anticoagulant (10% for the dose of 110 mg and 30% for the dose of 150 mg), without changes in the proportions of individuals regarding to gender (men ≅65%), age (age <75 anos ≅80%), anticoagulation previous history (≅85%) and risk scores for thromboembolic (CHA2DS2≥VASc = 2 ≅80%) and bleeding (HASBLED <3 ≅50% dose 110 mg and ≅85% dose 150 mg) events. The most common adverse event was dyspepsia (≥10%), regardless of gender, but less frequently in patients over 75 years of age (≅20% of cases). Dyspepsia related to dabigatran was mainly associated to its combination with beta-blockers (≅70%), but minoritarily with oral hypoglycemic (≅20%), antiplatelet agents (≅10%), proton pump inhibitors (≅30%) and antagonists H2 (≅3%). Therapeutic adherence was ≅60% regardless of the described adverse events. There were no cases of thromboembolic event and major bleeding. Conclusions: Dabigatran has shown to be safe and effective in the evaluated conditions.