Therapeutic Adherence According to the Morisky Scale in Patients with Hypertension

Abstract Background In view of the high prevalence of hypertension and the importance of adequate drug therapy in the prevention of complications, it is necessary to know the adherence to drug treatment in this population. Objective To verify adherence to antihypertensive drug treatment in Brazilian patients with hypertension using the Morisky-Green Test (MGT), relating it with demographic data. Methods Prospective, observational, multicenter, national registry study, with 2,578 hypertensive patients participating in study I, the Brazilian Cardiovascular Registry of Arterial Hypertension (I-RBH), recruited in the five regions of Brazil. The analyses carried out on the data were descriptive statistics, qui-square tests, ANOVA, and logistic regression, adopting 5% as the significance level for the tests. Results The research shows that 56.13% of patients in the sample were female; 56.71% were elderly (≥ 65 years); 55.86% were White; 52.37% were from the Southeast Region; and 59.74% were non-adherent. Logistic regression showed an independent relationship between patients' age, ethnicity, and region with medication adherence. Conclusion Adherence to treatment is the key to reducing high rates of cardiovascular complications. The study brings a successful outcome in the relationship between the factors ethnicity, age, and region of patients with hypertension and medication adherence. To this end, it is necessary to understand these factors, considering systematic evaluation in the care of patients with hypertension and other chronic non-communicable diseases. This study is a significant contribution to multidisciplinary teams, as it highlights which risk factors interfere with medication adherence, incorporating better strategies in health education.

The first Brazilian registry of hypertension

Abstract: A systematic, nationwide assessment of care of patients with hypertension in Brazil is needed. The objective of the First National Registry of Patients with Hypertension in Brazil (RBH) is to evaluate the clinical profile, treatment patterns, and outcomes of diagnosed hypertensive patients in the country. Hypertension affects almost one third of the adult population worldwide and is the leading risk factor for death and disability globally. 1-4 Registries indicate that almost half of hypertensive patients have blood pressure (BP) above the target level, 1-6 but many regions are underrepresented in these studies, especially low- and middle-income countries. 1-6 Most of the data for low- to middle-income countries such as Brazil come from cross sectional regional studies, not prospective national studies. 1,7,8 We conducted the First National Registry of Patients with Hypertension in Brazil (RBH) to evaluate the clinical profile, treatment patterns, and outcomes of patients in the country who have a diagnosis of hypertension.

The First Brazilian Registry of Hypertension.

A systematic, nationwide assessment of care of patients with hypertension in Brazil is needed. The objective of the First National Registry of Patients with Hypertension in Brazil is to evaluate the clinical profile, treatment patterns, and outcomes of diagnosed hypertensive patients in the country.

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.

BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. RESULTS: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

An indirect stereoselective analysis of nebivolol glucuronides in plasma by LC-MS/MS: Application to clinical pharmacokinetics.

Nebivolol is a racemate of the d-isomer responsible for ß1 adrenergic receptor antagonism and the l-isomer responsible for the release of nitric oxide from endothelial cells. Nebivolol is mainly metabolized to nebivolol glucuronide, which also contribute to the nebivolol ß1 adrenoreceptor antagonism. This study reports the development and validation of an indirect stereoselective method of analysis of nebivolol glucuronides in plasma by LC-MS/MS. The method was applied to the investigation of stereoselectivity in the glucuronidation of nebivolol in elderly hypertensive patients (n=11) CYP2D6 phenotyped as EM and treated with a single oral dose of the racemate. One-milliliter plasma aliquots spiked with internal standard (S)-(-)-metoprolol were incubated with 25µL of ß-glucuronidase (final concentration 2500unit/mL) at pH 5.0 for 16h at 37°C. Linearity for total nebivolol was 0.2-125ng of each isomer per mL plasma and permitted analysis of nebivolol glucuronide isomers up to 48h after administration of a single oral dose of 10mg racemate. Regarding to the nebivolol glucuronide isomers, higher plasma concentrations of the d-isomer were observed compared to the l-isomer (d/l AUC=5.4), explaining at least in part the plasma accumulation of unchanged l-nebivolol (l/d AUC=1.8). This study also showed metabolic glucuronide nebivolol/unchanged nebivolol ratios of approximately 6.5 for the l-isomer (AUC 65.3 vs 10.1ngh/mL) and approximately 62.1 (335.2 vs 5.4ngh/mL) for the d-isomer. Considering that d-nebivolol glucuronide also contributes for ß1 adrenergic receptor antagonism, future studies regarding PK-PD of nebivolol should evaluate not only plasma concentrations of unchanged nebivolol isomers but also glucuronide nebivolol isomers.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial.

BACKGROUND: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. METHODS AND RESULTS: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). CONCLUSIONS: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

OBJECTIVES: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. METHODS: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. RESULTS: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ±â€Š40.4 versus 16.2 ±â€Š26.7 mg, P = 0.09). CONCLUSION: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. CLINICAL TRIALS REGISTRATION NUMBER: NCT00971165.

Cardiovascular risk in white coat hypertension: an evaluation of the ankle brachial index.

The aim in this study was to identify the cardiovascular risk in patients suffering from white coat hypertension (WCH) by determining the ankle brachial index (ABI) with an automatic oscillometric sphygmomanometer. The study was undertaken in a Brazilian city between August 2010 and June 2011. The study variables were age, ethnic origin, marital status, education level, profession, weight, height, waist circumference, arm and ankle blood pressure (BP), and ABI. Analysis of variance was used for repeated measures and Tukey's test for multiple comparisons of means. The linear relationship between systolic BP levels and ankle brachial indices was verified using Pearson's correlation coefficient. Results were expressed as mean values ± standard errors of means, and differences were considered statistically significant when P < .05. Study participants were 135 subjects, including 37% normotensive, 37% hypertensive (HT), and 26% WCH patients. WCH individuals revealed intermediate risk in the analysis of the clinical variables. Alterations compatible with peripheral obstructive arterial disease and arterial calcification were observed only in the HT and WCH groups. These findings lead to the premise that WCH should not be viewed as a benign condition. The measurement of the ABI should be considered in the clinical approach of patients and professionals should use it as an instrument for cardiovascular risk assessment in routine health care delivery.

Metoprolol oxidation polymorphism in Brazilian elderly cardiac patients.

OBJECTIVES: The purpose of this study was to phenotype the CYP2D6 in elderly with heart disease classified as extensive metabolizer or poor metabolizers (PM) of metoprolol, develop and validate the method of analysis of metoprolol tartrate and its metabolite in urine using HPLC, and identify potential correlations between anthropometric factors with metabolic ratios of metoprolol/α-OH metoprolol in urine. METHODS: The sample was composed of 130 elderly individuals with a previously identified type of heart condition, with normal renal and hepatic functions. The urine of all the patients were collected 0-8 h after the administration of a pill of 100 mg of metoprolol to determine concentrations of metoprolol and α-hydroxymetoprolol. Those patients presenting a metabolic ratio greater than 12.6 were phenotyped as PM. KEY FINDINGS: The median age of patients was 71.0 years, with a minimum of 60 and maximum of 93 years old. Three patients (2.3%) were phenotyped as PM of metoprolol different from the rate (7-10%) of PM existing in the Caucasian population. CONCLUSIONS: Most of the studied individuals were women, and the proportion of elderly with heart disease classified as PM was smaller than what is usually found among Caucasian populations.

Adesão ao tratamento anti-hipertensivo: análise pelo teste de Morisky-Green / Adherence to anti-hypertensive treatment: an analysis using the Morisky-Green test / Adhesión al tratamiento anti-hipertensivo: análisis por test de Morisky-Green

Considerando que a adesão ao tratamento é um desafio para o controle da hipertensão arterial sistêmica (HAS), este estudo teve como objetivo caracterizar os sujeitos da pesquisa segundo as variáveis sóciodemograficas e econômicas e avaliar o nível de adesão pelo Teste de Morisky-Green. Trata-se de estudo descritivo transversal de abordagem quantitativa, realizado com 90 hipertensos em um Centro de Saúde. O instrumento utilizado para coleta de dados foi o Teste de Morisky-Green (TMG). Os resultados mostraram que 63,0% da amostra eram mulheres e a média de idade foi de 66 anos, sendo que 72,2% não apresentaram adesão ao tratamento medicamentoso, corroborando pesquisas realizadas sobre adesão. Conclui-se que este estudo pode proporcionar subsídios para intervenções sobre a assistência aos pacientes com HAS, com a finalidade de aumentar as taxas de adesão e a qualidade de vida.

Considering that treatment adherence is a challenge in controlling systemic hypertension (SH), the objective of this study was to characterize subjects according to sociodemographic and economic variables and assess the adherence level using the Morisky-Green Test. This descriptive, cross-sectional, quantitative study was performed with 90 hypertensive individuals at a Health Center. Data collection was performed using the Morisky-Green test (MGT). Results show that 63.0% of the sample were women, with a mean age of 66 years, 72.2% of which did not adhere to the drug treatment, thus corroborating with current research on adherence. In conclusion, this study can provide support for health care interventions to patients with SH, aiming to increase adherence rates and improve quality of life.

Considerando que la adhesión al tratamiento es un desafío para el control de la hipertensión arterial sistémica (HAS), este estudio tuvo como objetivo caracterizar a los sujetos de la investigación según las variables sociodemográficas y económicas y evaluar el nivel de adhesión con el Test de Morisky-Green. Se trata de un estudio transversal, de abordaje cuantitativo, realizado con 90 hipertensos en un Centro de Salud. El instrumento utilizado para la recolección de datos fue el Test de Morisky-Green (TMG). Los resultados mostraron que 63,0% de la muestra eran mujeres, con media etaria de 66 años, siendo que 72,2% no presentaron adhesión al tratamiento medicamentoso, condiciéndose estos datos con investigaciones realizadas sobre adhesión. Se concluye en que este estudio puede proporcionar ayuda para intervenciones sobre la atención a pacientes con HAS, con la finalidad de aumentar las tasas de adhesión y la calidad de vida.

Assessment of cardiovascular risk of patients with arterial hypertension of a public health unit.

OBJECTIVE: To assess the cardiovascular risk, using the Framingham risk score, in a sample of hypertensive individuals coming from a public primary care unit. METHODS: The caseload comprised hypertensive individuals according to criteria established by the JNC VII, 2003, of 2003, among 1601 patients followed up in 1999, at the Cardiology and Arterial Hypertension Outpatients Clinic of the Teaching Primary Care Unit, at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. The patients were selected by draw, aged over 20 years, both genders, excluding pregnant women. It was a descriptive, cross-sectional, observational study. The Framingham risk score was used to stratify cardiovascular risk of developing coronary artery disease (death or non-fatal acute myocardial infarction). RESULTS: Age range of 27-79 years (x = 63.2 +/- 9.58). Out of 382 individuals studied, 270 (70.7%) were female and 139 (36.4%) were characterized as high cardiovascular risk for presenting diabetes mellitus, atherosclerosis documented by event or procedure. Out of 243 stratified patients, 127 (52.3%) had HDL-C < 50 mg/dL; 210 (86.4%) had systolic blood pressure > or = 120 mmHg; 46 (18.9%) were smokers; 33 (13.6%) had a high cardiovascular risk. Those added to 139 enrolled directly as high cardiovascular risk, totaled up 172 (45%); 77 (20.2%) of medium cardiovascular risk and 133 (34.8%) of low risk. The highest percentage of high cardiovascular risk individuals was aged over 70 years; those of medium risk were aged over 60 years; and the low risk patients were aged 50 to 69 years. CONCLUSION: The significant number of high and medium cardiovascular risk individuals indicates the need to closely follow them up.

Análise dos custos de medicamentos no tratamento das dislipidemias em Ribeirão Preto, SP, Brasil / Analysis of dyslipidemia treatment drug costs in Ribeirão Preto, São Paulo State, Brasil

Fundamentos: As dislipidemias representam importante fator de risco para o desenvolvimento de doençascardiovasculares, comprovado por meio de grandes estudos observacionais.Objetivo: Analisar os custos de utilização de atorvastatina, sinvastatina, bezafibrato e ciprofibrato por indivíduospertencentes ao Programa de Medicamentos Excepcionais do Ministério da Saúde, distribuídos pelo Hospital das Clínicas de Ribeirão Preto, SP, Brasil, em 2007. Métodos: Estudo observacional, descritivo e de carátertransversal. Casuística composta por 332 (31,11%) indivíduos sorteados aleatoriamente dentre 1067 pacientes, de ambos os sexos, encaminhados pelo Sistema Único de Saúde (SUS) e consultórios particulares. Os indivíduos foram entrevistados e seus prontuáriosmédicos analisados. Resultados: Dos 312 pacientes entrevistados, 157 (51%) eram do sexo masculino. A faixa etária variou de 15-63 anos (62,0±12,23 anos). Fizeram uso de estatinas 227 (73,22%) pacientes; 54 (17,42%) de fibratos e 31 (10%)pacientes formavam o grupo-controle. O tratamento do grupo atorvastatina apresentou o maior custo (R$994,69paciente/ano), já no grupo da sinvastatina (R$337,61 paciente/ano) houve maiores gastos com exameslaboratoriais e complementares. No grupo dos fibratos, a categoria de medicamentos foi a que gerou maiorgasto em ambos os grupos. Os pacientes do grupo ciprofibrato apresentaram mais necessidade de exameslaboratoriais e complementares em relação ao grupo bezafibrato.Conclusões: O tratamento com atorvastatina foi o mais oneroso, entretanto, os pacientes apresentaram menor ocorrência de eventos e procedimentos cardiovasculares, além do menor custo com exames laboratoriais.

Assessment of cardiovascular risk of patients with arterial hypertension of a public health unit / Avaliação do risco cardiovascular de indivíduos portadores de hipertensão arterial de uma unidade pública de saúde

Objective: To assess the cardiovascular risk, using the Framingham risk score, in a sample of hypertensive individuals coming from a public primary care unit. Methods: The caseload comprised hypertensive individuals according to criteria established by the JNC VII, 2003, of 2003, among 1601 patients followed up in 1999, at the Cardiology and Arterial Hypertension Outpatients Clinic of the Teaching Primary Care Unit, at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. The patients were selected by draw, aged over 20 years, both genders, excluding pregnant women. It was a descriptive, crosssectional, observational study. The Framingham risk score was used to stratify cardiovascular risk of developing coronary artery disease (death or non-fatal acute myocardial infarction). Results: Age range of 27-79 years (x = 63.2 ± 9.58). Out of 382 individuals studied, 270 (70.7%) were female and 139 (36.4%) were characterized as high cardiovascular risk for presenting diabetes mellitus, atherosclerosis documented by event or procedure. Out of 243 stratified patients, 127 (52.3%) had HDL-C < 50 mg/dL; 210 (86.4%) had systolic blood pressure greater than or equal to 120 mmHg; 46 (18.9%) were smokers; 33 (13.6%) had a high cardiovascular risk. Those added to 139 enrolled directly as high cardiovascular risk, totaled up 172 (45%); 77 (20.2%) of medium cardiovascular risk and 133 (34.8%) of low risk. The highest percentage of high cardiovascular risk individuals was aged over 70 years; those of medium risk were aged over 60 years; and the low risk patients were aged 50 to 69 years. Conclusion: The significant number of high and medium cardiovascular risk individuals indicates the need to closely follow them up.

Objetivo: Identificar o risco cardiovascular, por meio do escore de risco de Framinghan, em uma amostra de hipertensos de uma unidade pública de saúde. Métodos: A casuística foi constituída por hipertensos, segundo critérios do JNC VII, 2003, de 2003, dentre 1.601 acompanhados no ano de 1999 no Ambulatório de Cardiologia e Hipertensão Arterial do Centro Saúde Escola da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Os pacientes foram selecionados por sorteio, com idade acima de 20 anos, ambos os gêneros, excluindo-se as gestantes. Tratou-se de estudo observacional descritivo e transversal. Utilizou-se o Escore de Risco de Framinghan para estratificação do risco cardiovascular para desenvolvimento de doença arterial coronária (morte ou infarto agudo do miocárdio - não fatal). Resultados: A idade variou de 27 a 79 anos (x = 63,2 ± 9,58). Dos 382 indivíduos estudados, 270 (70,7%) eram mulheres e 139 (36,4%) foram caracterizados como de alto risco cardiovascular por apresentarem diabetes mellitus, aterosclerose documentada por evento ou procedimento. Dos 243 estratificados, 127 (52,3%) apresentaram HDL-C < 50 mg/dL; 210 (86,4%) apresentaram pressão arterial sistólica maior ou igual a 120 mmHg; 46 (18,9%) eram fumantes; 33 (13,6%) eram de alto risco cardiovascular - que somados aos 139 incluídos diretamente como alto risco cardiovascular, totalizaram 172 (45%); 77 (20,2%) eram de médio risco cardiovascular e 133 (34,8%) de baixo risco. O maior percentual de indivíduos de alto risco cardiovascular situou-se acima 70 anos; de médio risco, acima de 60 anos; e de baixo risco entre 50 e 69 anos. Conclusão: O número significativo de indivíduos de alto e médio risco cardiovascular indica a necessidade de um acompanhamento mais próximo dos mesmos.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial.

BACKGROUND: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil. TRIAL REGISTRATION: Clinical Trials NCT00970931.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial.

BACKGROUND: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. METHODS/DESIGN: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov: NCT00971165.