Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud / Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease

Background: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. Aim: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. Material and Methods: Review of clinical records of patients with CKD in an urban primary care clinic. Results: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. Conclusions: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

A hipertensão e a medicina translacional / Hypertension in translacional cardiology

A nova fase de aceleração da transferência de conhecimento para a aplicação foi, simbolicamente, iniciada na década de 40, com o desenvolvimento da bomba atômica por um grupo notável de físicos. Na mesma época, o conhecimento transferido na Universidade de Stanford cria o Vale do Silício, onde se desenvolveu a indústria eletrônica com aplicação dos transistors. Logo, importantes universidades criam incubadoras e parques tecnológicos para acelerar a transferência do conhecimento para a aplicação, inaugurando-se a assim chamada Pesquisa Translacional. Na Medicina, só a partir do ano 2000, e com importante financiamento do National Institute of Health dos Estados Unidos, é que se inicia o movimento, sistematizando a transferência e criando-se a Medicina Translacional. Nessa revisão, apresentaremos dois exemplos de Medicina Translacional (Cardiologia Translacional) provenientes de pesquisas do nosso grupo de Hipertensão do Instituto do Coração (InCor). O primeiro ilustra a retroalimentação entre a pesquisa básica e a clínica, estudando a influência da hiperatividade da enzima conversora da angiotensina no desenvolvimento da hipertrofia cardíaca clínica (polimorfismo do gene da ECA) e em camundongos com uma, duas, três e quatro cópias do gene da enzima conversora, submetidos a natação ou coarctação da aorta. O segundo ilustra a transferência do conhecimento obtido na investigação clínica para a prática médica, com um estudo multicêntrico (25 centros do Brasil) sobre a prevalência da hipertensão resistente na população brasileira e a comparação da clonidina e espirolactona como quarta droga a ser administrada nos pacientes resistentes: Estudo Multicêntrico de Pacientes com Hipertensão Arterial para Identificação de Pacientes Resistentes e Padronização de Esquema Terapêutico. Os dois exemplos ilustram a importância das instituições (no caso, o InCor) propiciarem condições e ambientes favoráveis para que os profissionais de diferentes disciplinas (clínicos, fisiologistas, biologistas moleculares, bioengenheiros, enfermeiros, nutricionistas, fisioterapeutas, educadores físicos etc) trabalhem integrados e pratiquem a Cardiologia Translacional

The acceleration of the transfer of knowledge to application began symbolically in the 1940s, with the development of the atomic bomb by a notable group of physicists. In that same period, the knowledge transferred from Stanford University led to the creation of Silicon Valley, where the electronic industry was developed with the application of transistors. Soon afterwards, major universities created incubators and technology parks in order to accelerate the transfer of knowledge to application, inaugurating the concept of Translational Research. In the field of Medicine, the transfer systematization process began in 2000, with important funding from the US National Institute of Health, creating Translational Medicine. In this review, two examples of Translational Medicine (Translational Cardiology) from research by our Hypertension team of the Heart Institute (InCor) are presented. The first illustrates the feedback between basic and clinical research, studying the influence of the hyperactivity of the angiotensin converting enzyme in the development of clinical cardiac hypertrophy (polymorphism of the ACE gene) and in mice with one, two, three and four copies of the converting enzyme gene, submitted to swimming or aortic coarctation. The second illustrates the transfer of knowledge obtained in the clinical investigation to clinic practice with a multicenter trial (25 centers in Brazil) on the prevalence of resistant hypertension in the Brazilian population, and the comparison of clonidine and spirolactone as a forth drug to be administrated in resistant patients: Multicenter Study of Patients with Arterial Hypertension for Identification of Resistant Patients and Standardization of the Therapeutic Regimen. Both examples illustrate the importance of institutions (in this case, InCor) in providing a favorable environment and conditions for professionals from different disciplines (clinicians, physiologists, molecular biologists, bioengineers, nurses, nutritionists, physiotherapists, physical educators, etc.) to work in an integrated way and practice Translational Cardiology

Comunicação intercoronária: uma anomalia coronária rara / Intercoronary communication: a rare coronary abnormality

Comunicação intercoronária ou arcada coronária é uma anomalia congênita rara. Relatamos o caso de um paciente com comunicação intercoronária, com quadro de dor torácica e eletrocardiograma com padrão de repolarização ventricular precoce, mas sem aterosclerose significativa à cineangiocoronariografia. No entanto, foi visualizada comunicação intercoronária com fluxo unidirecional entre a coronária direita e a artéria circunflexa, que foi avaliada pela ecocardiografia sob estresse físico, sem detecção de isquemia. Embora a comunicação intercoronária geralmente não esteja relacionada à isquemia, há relatos na literatura de que o fluxo unidirecional pode causar isquemia miocárdica por meio do roubo coronariano.

Intercoronary communication or coronary arcade is a rare congenital abnormality. The authors report the case of a patient with intercoronary communication, chest pain, and electrocardiogram showing an early ventricular repolarization pattern, but no significant atherosclerosis at the coronary angiography. Nevertheless, an intercoronary communication with unidirectional flow between the right coronary artery and the left circumflex artery was visualized, and later assessed by physical stress echocardiography, which did not detect ischemia. Although intercoronary communication is usually unrelated to ischemia, there are reports in the literature that unidirectional flow can cause myocardial ischemia through coronary steal

The Effects of Oral Atenolol or Enalapril Premedication on Blood Loss and Hypotensive Anesthesia in Orthognathic Surgery

PURPOSE: The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent. MATERIALS AND METHODS: Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a beta blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 microg kg-1min-1) with sevoflurane. RESULTS: Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015). CONCLUSION: Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.

Add-on treatment with nebulized hypertonic saline in a child with plastic bronchitis after the Glenn procedure / Tratamento adjuvante com nebulização de salina hipertônica em uma criança com bronquite plástica após a operação de Glenn

Plastic bronchitis (PB), although a rare cause of airway obstruction, has mortality rates up to 50% in children after Fontan-type cardiac surgery. We present the case of an 18-month-old female patient with PB following pneumonia. At 6 months of age, the patient underwent the Glenn procedure due to functionally univentricular heart. Fiberoptic bronchoscopy revealed complete blockage of the left bronchus by mucoid casts. Pharmacotherapy consisted of glucocorticosteroids, azithromycin, and enalapril maleate. The child also received nebulized 3% NaCl solution, which proved to be beneficial. In children submitted to Fontan-type procedures, physicians must be alert for PB, which can be triggered by respiratory tract infection.

A bronquite plástica (BP), embora uma causa rara de obstrução de vias aéreas, apresenta taxas de mortalidade de até 50% em crianças submetidas a cirurgia cardíaca do tipo Fontan. Apresentamos o caso de uma menina de 18 meses de idade com BP secundária a pneumonia. Aos 6 meses de idade, a paciente havia sido submetida à operação de Glenn devido a coração funcionalmente univentricular. A fibrobroncoscopia revelou obstrução completa do bronco esquerdo por moldes mucoides. A farmacoterapia consistiu em glicocorticosteroides, azitromicina e maleate de enalapril. Adicionalmente, a criança recebeu nebulização de solução de NaCl a 3%, que provou ser benéfica. Em crianças submetidas a operações do tipo Fontan, devemos nos manter alerta quanto à BP, que pode ser desencadeada por infecção do trato respiratório.

Uso a longo prazo de enalapril e hidroclorotiazida em dois pacientes com novas mutações com doença de Dent tipo 1 / The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1

A doença de Dent é uma tubulopatia ligada ao X causada por mutações no gene que codifica o canal de cloro CLCN-5 e é caracterizada por proteinúria de baixo peso molecular, hipercalciúria, nefrocalcinose e insuficiência renal. Vários casos têm sido descritos, nos quais o único sintoma na apresentação foi proteinúria assintomática e glomerulosclerose global ou segmentar. A insuficiência renal nesses pacientes pode ser causada pela hipercalciúria e proteinúria persistente. Portanto, o inibidor da enzima de conversão da angiotensina e os tiazídicos poderiam ser úteis. O objetivo desta pesquisa é relatar os efeitos destas drogas em dois pacientes com doença de Dent tipo 1 com mutações novas. Neste relato não foram observadas correlações significativas entre dose de hidroclorotiazida e calciúria e entre enalapril e proteinúria. Este achado é importante, pois, sendo pacientes poliúricos, o uso destas drogas poderia prejudicar a função renal.

Dent's disease type 1 is an X-linked tubular disease caused by mutations in the renal chloride channel CLCN-5, and it is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal failure. Several cases have been described in which the only presenting symptoms were asymptomatic proteinuria, and focal segmental or global glomerulosclerosis. The renal failure in these patients may be caused by hypercalciuria and persistent proteinuria. Therefore, angiotensin converse enzyme inhibitor and thiazides could be useful. Our aim is to report the effects of these drugs in two novel mutations patients with Dent's disease type 1. In this report, no significant correlations between dosage of hydrochlorothiazide and calciuria and no significant correlations between proteinuria and dosage of enalapril were detected. This is important since these are polyuric patients and these drugs could be dangerous to their renal function.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Padrões de prescrição de inibidores da enzima conversora da angiotensina para usuário do Sistema Único de Saúde / Prescription patterns of angiotensin converting enzyme inhibitors for unified health system users

Fundamentos: Os inibidores da enzima conversora da angiotensina são frequentemente prescritos para o tratamento da hipertensão arterial sistêmica e da insuficiência cardíaca congestiva. Os dois primeiros representantes dessa classe, o captopril e o enalapril, constam na Relação Nacional de Medicamentos Essenciais devido à eficácia clínica, segurança comprovada e custo-efetividade. Objetivo: Analisar os padrões de prescrição de captopril e de enalapril para os usuários do Sistema Único de Saúde no Distrito Sanitário Oeste de Ribeirão Preto. Métodos: Realizou-se um levantamento no banco de dados da Secretária Municipal de Saúde de Ribeirão Preto para quantificar os usuários do Sistema Único de Saúde que receberam a prescrição de captopril e do enalapril, a frequência de dispensação e analisaram-se os esquemas terapêuticos no peródo entre 01/03/2006 e 28/02/2007. Os dados foram submetidos à análise de variância e aos teste t de Student e de comparações múltiplas de médias. Resultados: Identificou-se que 9560 pacientes utilizaram os inibidores da enzima conversora da angiotensina, sendo quedestes, 46,57% utilizaram captopril, 45,74% enalapril e 7,69% os dois fármacos simultaneamente ou não. A idade média dos usuários foi 61 anos e a utilização desses agentes aumentou progressivamente com o aumento da faixa etária. As doses médias prescritas de captopril foram 69,9mg/dia e de enalapril, 21,35mg/dia e um total de 41,57% dos pacientes apresentaram risco de apresentar interação medicamentosa. Conclusões: Atualmente, existe uma preferência deprescrição de inibidores da enzima conversora da angiotensina em unidades públicas de saúde devido à sua relevânciaterapêutica para o tratamento de doenças crônicas.

Background: Angiotensin-converting enzyme inhibitors are often prescribed for the treatment of systemic arterialhypertension and congestive heart failure. The first two repesentatives of this class, enalapril and captopril, are inthe National Essential Drugs List because of their clinical efficacy, proven safety and cost effectiveness. Objective: To analyze the prescription patterns ofcaptopril and enalapril for Government Health System users in the West Public Health District of Ribeirão Preto, São Paulo State. Methods: A survey was conducted of the Ribeirão PretoMunicipal Health Bureau database, in order to quantify Government Health System users receiving prescriptionsfor captopril and enalapril, with dispensing frequency and therapeutic schemes between 01/03/2006 and28/02/2007. The data underwent variance analysis and Student t tests, with multiple mean comparisons. Results: 9,560 patients were identified as taking angiotensin-converting enzyme inhibitors, of whom 46.57% took captopril, 45.74% enalapril and 7.69% both medications, either simultaneously or not. The averagepatient age was 61 years and the use of these agents rose progressively with increasing age. The mean doses prescribed were 69.9 mg/day for captopril and 21.35 mg/day for enalapril, with 41.57% of patients at risk for potential drug-drug interactions.Conclusion: Currently, there is a preference for prescribing ACE inhibitors at public health units in Ribeirao Preto due to their therapeutic relevance for thetreatment of chronic diseases.

Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana / Combination of amlodipine and enalapril in hypertensive patients with coronary disease / Combinación de amlodipino y enalapril en pacientes hipertensos con enfermedad coronaria

FUNDAMENTO: Pacientes (pts) com doença coronariana (DAC) estável podem se beneficiar de menor pressão arterial (PA), conforme estudos recentes. OBJETIVO: Avaliar a eficácia e a tolerabilidade da combinação fixa anlodipino + enalaprila, comparada a anlodipino na normalização da PA diastólica (PAD) (< 85 mmHg), em pts com DAC e HAS. MÉTODOS: Estudo duplo-cego, randomizado, com dois grupos de pts com PAD > 90 e <110 mmHg e DAC. Excluímos os com FEVE < 40%; sintomas de insuficiência cardíaca ou angina classe III e IV; doenças graves e PAD > 110 mmHg durante o wash-out de quatro semanas, em uso só de atenolol. Após wash-out randomizamos para combinação (A) ou anlodipino (B) e seguimos de quatro em quatro semanas até 98 dias. As doses (mg) iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatística com χ2, Fischer e análise de variância, para p< 0,05. RESULTADOS:de 110 pts selecionados, randomizamos 72 (A= 32, B= 40). As reduções da PAD e da PA sistólica (PAS) foram intensas (p< 0,01), mas sem diferenças entre os grupos em mmHg: PAS, A (127,7 ± 13,4) e B (125,3 ± 12,6) (p= 0,45) e PAD, A (74,5 ± 6,7 mmHg) e B (75,5 ± 6,7 mmHg) (p= 0,32). Houve menos edema de membros inferiores no A (7,1% vs 30,6%, p=0,02) no 98º dia. CONCLUSÃO: A combinação fixa de enalaprila com anlodipino, tal qual anlodipino isolado, em pts com DAC e HAS estágios I e II foi eficaz na normalização da pressão, adicionando bloqueio ao sistema renina-angiotensina.

BACKGROUND: Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic arterial hypertension (SAH). METHODS: Double-blind and randomized study, with two groups of pts with DAP >90 and <110 mmHg and CAD. Patients with left ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina class III and IV, severe diseases and DAP >110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with χ2, Fischer and analysis of variance, for p< 0.05. RESULTS: Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 ± 13.4) and B (125.3 ± 12.6) (p= 0.45) and DAP, A (74.5 ± 6.7 mmHg) and B (75.5 ± 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up. CONCLUSION: The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.

FUNDAMENTO: Pacientes (pts) con enfermedad coronaria (EAC) estable pueden beneficiarse con una menor presión arterial (PA), de acuerdo con estudios recientes. OBJETIVO: Evaluar la eficacia y la tolerancia de la combinación fija amlodipino + enalapril, comparada a el amlodipino en la normalización de la PA diastólica (PAD) (< 85 mmHg), en pts con EAC y HAS. MÉTODOS: Estudio doble ciego, randomizado, con dos grupos de pts con PAD >90 y <110 mmHg y EAC. Excluimos a los pts con FEVI < 40%; síntomas de insuficiencia cardiaca o angina clase III y IV; enfermedades graves y PAD >110 mmHg durante el wash-out de cuatro semanas, en uso sólo de atenolol. Después del wash-out randomizamos para combinación (A) o amlopidino (B) y seguimos de cuatro en cuatro semanas hasta 98 días. Las dosis (mg) iniciales fueron, respectivamente: A- 2,5/10 y B- 2,5, siendo incrementadas si PAD> 85mmHg, en las visitas. Estadística con χ2, Fischer y análisis de varianza, para p< 0,05. RESULTADOS: De un total de 110 pts seleccionados, randomizamos a 72 (A= 32, B= 40). Las reducción de la PAD y de la PA sistólica (PAS) fueron intensas (p< 0,01), pero sin diferencias entre los grupos en mmHg: PAS, A (127,7 ± 13,4) y B (125,3 ± 12,6) (p= 0,45) y PAD, A (74,5 ± 6,7 mmHg) y B (75,5 ± 6,7 mmHg) (p= 0,32). Se registró menos edema de miembros inferiores en el A (7,1 por ciento vs 30,6%, p=0,02) en el 98º día. CONCLUSIÓN: La combinación fija de enalapril con amlodipino, tal como el amlodipino aislado, en pts con EAC y HAS estadios I y II fue eficaz en la normalización de la presión, agregando un bloqueo al sistema renina-angiotensina.

Eficacia del Enalapril en pacientes monorrenos con dieta normoproteica y sin ella / Efficacy of Enalapril in patients with single kidney and with or without normoprotein diet

El paciente monorreno, sin dieta normoproteica,puede presentar microalbuminuriaanormal con eventual desarrollo de glomerulosclerosis.Objetivo. Evaluar la eficacia del Enalapril parareducir la microalbuminuria patológica en pacientesmonorrenos con dieta normoproteica y sin ella.Población, material y métodos. Estudiamos 49 pacientesmonorrenos, edad (media) 11 años, eutróficos,con función renal normal y consentimiento médicoaprobado. Criterios de exclusión: uropatías,hipertensión arterial, enfermedades oncológicas, tratamientoscon drogas nefrotóxicas, proteinuriaortostática. La población se clasificó en dos grupos:Grupo A: con dieta normoproteica (0,8-1,2 g/kg/díapara sexo y edad). Grupo B: con dieta libre.A los pacientes con microalbuminuria anormal seles administró Enalapril (intervalo de dosis: 0,1 mg/kg/día a 0,3 mg/kg/día).Resultados. Grupo A: 21 pacientes, 2 con microalbuminuriapatológica. Aumento promedio del tamañorenal: 14% (DE 8 por ciento). Riesgo de presentarmicroalbuminuria patológica: 9 porc ciento.Grupo B: 28 pacientes, 11 con microalbuminuriaanormal. Riesgo de presentar microalbuminuriaanormal: 40 por ciento. Aumento promedio del tamaño renal:33,8 (DE 6,1 por ciento). RR: 4,125(IC 1-16) (p: 0,01).NND: 3. Media de microalbuminuria pre-Enalapril50,20 μg/minuto y post-Enalapril 11,5 μg/minuto.Dosis media de Enalapril: 0,2 mg/kg/día.Coeficiente de correlación entre microalbuminuriay aumento del tamaño renal: 0,75; y entre ingestaproteica y aumento del tamaño renal: 0,72.Tiempo (medio) de aparición de la microalbuminuriaanormal: 81 meses (DE 7 meses).Conclusión. El Enalapril junto con la dieta normoproteicaen pacientes monorrenos disminuyen elriesgo de desarrollar microalbuminuria anormal

Efeito a curto prazo do losartan comparado ao enalapril na função ventricular esquerda e na capacidade de pacientes com insuficiência aórtica crônica grave oligo grave ou assintomáticos / Effect in short term of losartan compared with the enalapril in the left ventricular function and the physical capacity of patients with asymptomatic or minimally symptomatic chronic severe aortic regurgitation

Objetivo: analisar o efeito a curto prazo do lasartan comparado ao enalapril sobre a função ventricular esquerda em pacientes com insuficiência valvar aórtica grave, oligo ou assintomáticos, testar a segurança do lasartan nessas condições e estudar o impacto destas drogas sobre a capacidade física. Métodos: Dez pacientes com insuficiência valvar aórtica (IAo)crônica grave e com função ventricular esquerda preservada (fração de ejeção menor ou igual 0,55), foram estudados de forma prospectiva em um estudo de intervenção medicamentosa cross-over, comparando-se duas drogas: losartan e o enalapril, através de avaliação clínico-laboratorial, ecocardiograma de repouso e teste cardiopulmonar em três momentos diferentes: sem medicação, em uso de losartan, em uso de enalapril. Resultados: Foram estudados 7 (70 por cento homens e 3 (30 por cento) mulheres com idade entre 15 e 41 anos (média de 26 anos). A dose média diária de enalapril foi de 38mg com tempo médio de 3,9 meses e a de losartan foi de 90mg com tempo médio de três meses. Não houve efeitos adversos graves....

The relationship between heart rate reserve and oxygen uptake reserve in heart failure patients on optimized and non-optimized beta-blocker therapy

BACKGROUND: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients either on non-optimized or off beta-blocker therapy is known to be unreliable. The aim of this study was to evaluate the relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients receiving optimized and non-optimized beta-blocker treatment during a treadmill cardiopulmonary exercise test. METHODS: A total of 27 sedentary heart failure patients (86 percent male, 50±12 years) on optimized beta-blocker therapy with a left ventricle ejection fraction of 33±8 percent and 35 sedentary non-optimized heart failure patients (75 percent male, 47±10 years) with a left ventricle ejection fraction of 30±10 percent underwent the treadmill cardiopulmonary exercise test (Naughton protocol). Resting and peak effort values of both the percentage of oxygen consumption reserve and percentage of heart rate reserve were, by definition, 0 and 100, respectively. RESULTS: The heart rate slope for the non-optimized group was derived from the points 0.949±0.088 (0 intercept) and 1.055±0.128 (1 intercept), p<0.0001. The heart rate slope for the optimized group was derived from the points 1.026±0.108 (0 intercept) and 1.012±0.108 (1 intercept), p=0.47. Regression linear plots for the heart rate slope for each patient in the non-optimized and optimized groups revealed a slope of 0.986 (almost perfect) for the optimized group, but the regression analysis for the non-optimized group was 0.030 (far from perfect, which occurs at 1). CONCLUSION: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in patients on optimized beta-blocker therapy was reliable, but this relationship was unreliable in non-optimized heart failure patients.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy / Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria more than 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 more or less 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 more or less 1.86 g/day; serum creatinine 1.07 more or less 0.29 mg/dl; mean follow-up 60.10 more or less 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 more or less 0.07 g/day (P less than 0.001) while serum creatinine did not vary: 1.07 ± 0.28 mg/dl (P=ns). After a mean follow-up of 42.36 more or less 21.56 months urinary protein excretion (0.12 more or less 0.06 g/day) and renal function (serum creatinine 1.06 more or less 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to less than 0.5 g/day in patients with IgA nephropathy without changes in renal function.

El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias major que 0.5 g/día y creatininas séricas menor que 1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a menor que 0.5 g/día. Fueron incluidos 20 pacientes: Edad: 37.45 más o menos 13.3 años (50% hombres); 7 pacientes (35%) eran hipertensos; proteinuria inicial 2.2 más o menos 1.86 g/día; creatinina inicial 1.07 más o menos 0.29 mg/dl; seguimiento promedio: 60.10 más o menos 31.47 meses (5 más o menos 2.62 años). La nefropatía por IgA fue subclasificada según Haas: 12 pacientes (60%) clase II; 7 (35%) clase III y 1 (5%) clase V. Todos recibieron enalapril más valsartán según tolerancia más metilprednisona vía oral en dosis de 0.5 mg/kg/día durante las primeras 8 semanas y subsecuentemente se redujo cada dos semanas hasta llegar a 4 mg. Se discontinuaron los esteroides luego de 24 semanas (6 meses). La inhibición del sistema renina angiotensina prosiguió indefinidamente. A las 10 semanas la proteinuria disminuyó de 2.2 más o menos 1.86 g/día a 0.15 más o menos 0.7 g/día (p menor que 0.001); la creatinina no varió significativamente (1.07 más o menos 0.29 mg/dl vs. 1.07 más o menos 0.28 mg/dl) (P=ns). Luego de 10 semanas y con un seguimiento de 42.36 más o menos 21.56 meses la proteinuria (0.12 más o menos 0.006 g/día) y la función renal (creatinina 1.06 más o menos 0.27mg/dl) permanecieron estables. No se informaron efectos adversos durante el estudio. El doble bloqueo del sistema renina angiotensina más bajas dosis de metilprednisona resultó útil para reducir...

Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores / Heart failure treatment profile at the beta blockers era

OBJETIVOS: A inibição dos sistemas renina-angiotensina-aldosterona (SRAA) e sistema nervoso autônomo simpático aumentou a perspectiva de sobrevida desses pacientes, além de permitir substancial melhora na qualidade de vida. O objetivo deste trabalho foi avaliar a realidade do tratamento aplicado e seu impacto sobre a doença em pacientes acompanhados em um ambulatório especializado em insuficiência cardíaca(IC). MÉTODOS: Foram estudados 96 pacientes acompanhados no ambulatório de Insuficiência Cardíaca e Transplante do Instituto do Coração, do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Os dados foram coletados durante a consulta ambulatorial a partir de prontuário médico e exame clínico. A escolha dos pacientes foi aleatória. RESULTADOS: A maior parte dos pacientes encontrava-se em classe funcional II (42,3 por cento) e em estágio C de evolução (94,9 por cento). A prescrição médica para os pacientes foi bastante próxima do preconizado pelas diretrizes. Aproximadamente 95 por cento recebem inibidores do SRAA (inibidor de ECA - enalapril e captopril - ou antagonista dos receptores de angiotensina-losartan), enquanto 85 por cento dos pacientes recebem, além desses, agentes betabloqueadores (carvedilol). A dose média prescrita também se aproxima das utilizadas nos grandes estudos, e atinge mais de 60 por cento da dose máxima de cada medicação. Os dados hemodinâmicos encontrados mostram pacientes estáveis, apesar da intensidade da disfunção e do remodelamento ventricular destes. CONCLUSÃO: Pacientes portadores de IC acompanhados por equipe médica especializada têm prescrição médica mais próxima do preconizado. Esses pacientes, embora com características marcadas de gravidade da doença, conseguem estabilidade hemodinâmica e clínica com a otimização terapêutica adequada.

OBJECTIVES: The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. METHODS: A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS: Most of the patients were Functional Class II (42.3 percent) and evolution stage C (94.9 percent). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95 percent of them received RAAS inhibitors (ACE inhibitor - enalapril and captopril - or angiotensin receptor antagonist - losartan), whereas 85 percent of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60 percent of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION: Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

Disfunção do eletrodo ventricular ocasionando "tempestade" de choques inapropriados e depleção precoce da bateria do cardioversor-desfibrilador implantável / Ventricular electrode dysfunction causing inappropriate

Paciente sexo masculino, com 54 anos de idade, portador de cardioversor-desfibrilador. Após dois anos e dez meses de evolução, apresentou "tempestade" de 80 choques inapropriados, de forma intermitente e persistente, em um período de três horas e meia. A análise eletrônica do sistema evidenciou disfunção do eletrodo de choque e desgaste da bateria, sendo realizada a troca do eletrodo e do gerador comprometidos...

The Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors in Severe Non-proliferative Diabetic Retinopathy

PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE-I) in retarding progression of severe non-proliferative diabetic retinopathy (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a retrospective case control study of 128 patients with normotensive type 2 diabetes with lower than +1 dipstick proteinuria and severe NPDR who were classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 , Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b) development of proteinuria of higher than +1 level requiring medication of ACE-I. RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and 99 ACE-I untreated patients. There were no differences in the average age, duration of diabetes, body mass indices, blood pressure and levels of hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in both groups remained unchanged during the study. The mean follow-up period was 41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6 developed proteinuria of greater than +1 over the follow-up period. In the control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I did not yield any beneficial effects in retarding the progression of severe NPDR.