Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension / Seguridad y eficacia de fimasartán en pacientes mexicanos con hipertensión esencial de grados 1-2

Abstract: Objective: To evaluate efficacy and safety of 60 mg and 120 mg Fimasartan (FMS) alone or combined with 12.5 mg hydrochlorothiazide (HCTZ) in a Mexican population. Methods: A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60 mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90 mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90 mmHg were randomised to either 120 mg FMS or 60 mg FMS + 12.5 mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90 mmHg received 120 mg FMS + 12.5 mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. Results: FMS 60 mg (n = 272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3 ± 8.9 (p<.0001) and 16.0 ± 14.1 (p<.0001) mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120 mg, FMS 60 mg + HCTZ 12.5 mg, or FMS 120 mg + HCTZ 12.5 mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP < 90 mmHg and an SBP<140 mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). Conclusion: Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.

Resumen: Objetivo: Evaluar la eficacia y la seguridad de 60 y 120 mg de fimasartán (FMS) solo o combinado con 12.5 mg de hidroclorotiazida (HCTZ) en población mexicana. Métodos: Estudio abierto, de 24 semanas, con tratamiento escalado hasta el objetivo terapéutico en sujetos hipertensos grados 1-2. Tratamiento inicial: FMS 60 mg una vez al día; en la semana 8, los sujetos con presión arterial diastólica (PAD) <90 mmHg mantuvieron su tratamiento inicial durante el estudio, mientras que los sujetos con PAD ≥90 mmHg fueron aleatorizados a 120 mg de FMS o a 60 mg de FMS + 12.5 mg de HCTZ. En la semana 12, los sujetos aleatorizados con PAD ≥90 mmHg recibieron 120 mg de FMS + 12.5 mg de HCTZ; quienes alcanzaron el objetivo terapéutico mantuvieron su tratamiento asignado hasta finalizar el estudio. Resultados: FMS 60 mg (n = 272) disminuyó la PAD y la presión arterial sistólica (PAS) en 11.3 ± 8.9 (p < 0.0001) y 16.0 ± 14.1 (p < 0.0001) mmHg, respectivamente, con logro del objetivo de tratamiento en el 75.4% de los sujetos. Los sujetos asignados a 120 mg de FMS, a 60 mg de FMS + 12.5 mg de HCTZ 12.5 y a 120 mg de FMS + 12.5 mg de HCTZ mostraron reducciones significativas de PAD y PAS; al final del estudio, 237/272 sujetos (87.1%) lograron PAD <90 y PAS <140 mmHg. Las reacciones adversas más frecuentemente reportadas fueron: cefalea (3.7%), boca seca (1.1%), incremento de enzimas hepáticas (1.1%) y mareo (0.7%). Conclusión: FMS es seguro y eficaz en sujetos mexicanos con hipertensión esencial de grados 1-2.

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results.

Desenvolvimento de sistemas multiparticulados de liberação imediata e modificada para associação de fármacos anti-hipertensivos / Development of immediate and modified release multiparticulate systems for antihypertensive drugs association

Os sistemas multiparticulados são aqueles nos quais a dose do fármaco está dividida em pequenas unidades funcionais, tendo assim, uma série de vantagens sobre os sistemas monolíticos convencionais. Este trabalho teve por objetivo desenvolver formulações multiparticuladas de uso oral para fármacos anti-hipertensivos que serão utilizados na composição de associações. O material está dividido em seis capítulos, sendo inicialmente apresentada uma revisão da literatura a respeito da caracterização física destas pequenas unidades. Ensaios como análise granulométrica, morfologia, densidade, porosidade, avaliação de resistência mecânica e desintegração são os mais empregados para esta finalidade, possibilitando ao formulador conhecer os fatores de maior impacto relacionados às matérias primas e ao processo de fabricação no comportamento das formulações produzidas. Os demais capítulos seguem com o desenvolvimento dos sistemas multiparticulados, que foram embasados em diferentes delineamentos experimentais, seja pela utilização de planejamento fatorial fracionado ou projeto de mistura. Para o metoprolol, fármaco de alta solubilidade, foram produzidas formulações de liberação controlada, sendo a estratégia dividida em três etapas: (I) Produção de minicomprimidos revestidos, nos quais foram avaliadas diferentes combinações do polímero modulador de liberação; (II) otimização do perfil de liberação do fármaco, com avaliação de misturas das formulações produzidas na primeira etapa; (III) Processo de extrusão a quente, no qual diferentes proporções de fármaco e polímero hidrofóbico foram avaliadas. Para os fármacos hidroclorotiazida e olmesartana medoxomila, ambos de baixa solubilidade, a estratégia adotada foi a incorporação de uma dispersão dos fármacos e agentes solubilizantes em grânulos inertes obtidos por extrusão/revestimento. Adicionalmente, também foram produzidas formulações por extrusão a quente de diferentes proporções destes fármacos em polímero hidrofílico. De acordo com os resultados obtidos, foi possível obter formulações de minicomprimidos e grânulos com perfil de dissolução satisfatório, semelhantes aos apresentados pelos medicamentos adotados como referência. Em relação à extrusão a quente foi possível avaliar a influência do processo e polímeros empregados no perfil de dissolução dos grânulos produzidos

Multiparticulate systems are dosage forms in which dose is divided into small functional units presenting some advantages over monolithic conventional systems. The objective of this work was developing multiparticulate formulations for oral use containing antihypertensive drugs to be used in association. The thesis is divided into six issues, been first presented a literature review about physical characterization of multiparticulate systems. Granulometric analysis, morphology, density, porosity, mechanical strength and disintegration are the most used physical characterization tests, enabling formulator knowing the major impact factors related to raw materials and manufacturing process in the performance of the produced formulations. The other issues present the development of the multiparticulate systems based on different statistical experimental design, as fractional factorial design or mixture project. For metoprolol, a highly soluble drug, controlled release formulations were obtained, and the strategy was divided into three steps: (I) coated minitablets production, where different combinations of the controlled release polymer were analyzed; (II) drug release profile optimization, evaluating formulations mixtures produced in the first step; (III) hot melt extrusion process, where different drug: hydrophobic polymer ratios were evaluated. For hydrochlorothiazide and olmesartan medoxomil, both low soluble drugs, the strategy was incorporating a dispersion containing the drugs and solubilizing agents in inert granules obtained by extrusion/coating processes. Additionally, formulations containing different ratios of these drugs and hydrophilic polymers were produced by hot melt extrusion. According to the results, it was possible to obtain minitablets and granules with good dissolution profile, similar to the reference products. Regarding to hot melt extrusion, it was possible to evaluate the influence of process and polymers used in the dissolution profile of the produced granules

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.

comparative study of the management of stage 2 hypertension by combined therapy with losartan, amlodipine and hydrochlorothiazide

The most effective and accurate treatment of hypertensive patients reduces cardiovascular events and improves the quality of life. This study compared the efficacy and safety of combined [combination therapy] with an angiotensin-receptor blocker [ARB] a calcium-channel blocker [CCB] [Losartan / Amloidipine 50/10mg] vs maximal combination doses of ARB with hydrochlorothiazide [Losartan /HCTZ 100/25 mg] and maximal combination doses of CCB with HCTZ [Amlodipine /HCTZ 10/25 mg] in the management of stage 2 hypertension. This randomized clinical trial [RTC] comprised 478 hypertensive patients with mean age 50.5 +/- 5.21 years, and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar. Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position >/= 160 and <200 mmHg in systole and >/= 100 and <110 mmHg in diastole were randomized into three groups: Losartan / Amlodipine 50/10 mg [n =164], Losartan / HCTZ 100/25 mg [n =155] and Amlodipine / HCTZ 10/25 mg [n =159]. The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group. There was a significant difference in systolic blood pressure reductions between treatment groups [P<0.001] and also there was a significant difference between groups in reducing diastolic blood pressure [P<0.01]. The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group. The ANCOVA analysis revealed that only treatment regimen had a significant effect [P=0.01] and other factor including Age, Gender, Diabetes Mellitus, Smoking and High serum cholesterol didn't have significant effect on blood pressure reduction. ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study

Hidroclorotiazida y espironolactona reducen la hipertrofia de la pared aórtica en la hipertensión arterial experimental / Diuretics are important and effective antihypertensive agents: however, there are a few studies assessing its role on the arterial wall remodelling in hypertension

Introducción: Los diuréticos forman parte del tratamiento antihipertensivo actual con efectividad e impacto clínico demostrados. Sin embargo, los efectos de estos fármacos sobre el remodelado de la pared arterial en la hipertensión arterial (HTA) han sido poco evaluados. Objetivos: Determinar y comparar el efecto de Hidroclorotiazida (HCTZ) y de Espironolactona (ESP) en la hipertrofia de la pared aórtica en la HTA experimental. Metodología: Estudio comparativo en 4 grupos experimentales. Se utilizaron ratas Sprague Dawley macho de 150 +/- 10 grs. unifrectomizadas tratadas con desoxicorticosterona Acetato (DOCA, 100 mg/Kg/sem sbc) por 6 semanas. Como controles (Sham) se usaron ratas unifrectomizadas. A partir de la tercera semana con DOCA se administró diuréticos en dos grupos adicionales durante 3 semanas. Uno recibió HCTZ (6 mg/ kg/día) y otro ESP (100 mg/Kg/dia), vía gavage. Al finalizar los tratamientos se determinó la presión arterial sistólica (PAS), masa corporal (MC), peso del corazón (PC) y masa cardiaca relativa (MCR). El grado de hipertrofia de la pared aórtica se determinó midiendo el grosor de la túnica media (GTM), área de la túnica media (ATM), área luminal (AL) y la relación ATM/AL en cortes teñidos con hematoxilina-eosina. Resultados: En las ratas DOCA no tratadas hubo un aumento significativo de PAS (51 por ciento), MCR (79 por ciento), ATM (44 por ciento), GTM (57 por ciento), y de la razón ATM/AL (43 por ciento) respecto al grupo Sham. Ambos tratamientos (Hctz y Esp) redujeron en forma muy importante y significativamente la PAS, MCR, ATM, GTM y la razón ATM/AL en magnitudes similares y también por cada mm de Hg de descenso de la PAS logrado. Conclusión: Además del efecto antihipertensivo, tanto hidroclorotiazida como espironolactona previenen y/o revierten en magnitud similar el desarrollo de hipertrofia de la pared aórtica en este modelo de HTA experimental.

Aims: To determine and compare the effects of hydrochlorotiazide (Hctz) and spironolactone (Esp) on hypertrophy of the aortic wall in experimental hypertension. Methods: This was a comparative study with 4 experimental groups. We used male. uninephrectomized Sprague Dawley rats (150 +/- 10 grs) treated with des-oxycorticosterone acetate (DOCA, 100 mg/Kg/week sbc) during 6 weeks. As controls uninephrectomized rats (Sham) were used. Starting from the third week with DOCA, two groups recived diuretics by gavage during 3 weeks. One group received Hctz (6 mg/kg/ day) and other group received Sp (100 mg/kg/day). At the end of the study, systolic blood pressure (SBP), body weight, heart weight and relative cardiac weight were measured. Hypertrohy in the aortic wall was assessed by measuring the media thickness (MT), media area (MA), lumen area (LA) and by the AM/LA ratio on hematoxyline-eosine stained cross sections. Results: Compared to the Sham group, in the untreated hypertensive DOCA group, SBP and relative cardiac weight increased significantly (by 51 percent and 79 percent, respectively), MA increased by 44 percent, as well as MT (57 percent) and the AM/LA ratio (43 percent). Both treatments (Hctz and Sp) reduced importantly and significantly SBP, relative cardiac mass as well as MT, MA and the AM/LA ratio at a similar extent and by mm Hg. Conclusion: Besides the antihypertensive effect, both hydrochlorotiazide and spironolactone prevent and/or regress aortic wall hypertrophy in this experimental model of hypertension.

Alteración del sodio y potasio en pacientes hospitalizados por insuficiencia cardíaca / Alteration of sodium and potassium levels in patients hospitalized for heart failure

La insuficiencia cardíaca es un síndrome ocasionado por múltiples factores y va produciendo un proceso de remodelado ventricular. Es un verdadero problema de salud pública que incrementa el número de hospitalizaciones. Los diuréticos siguen siendo útiles en el tratamiento, aún así se producen alteraciones de los electrólitos que pueden ocasionar arritmias, empeoramiento de la insuficiencia cardíaca y disminución de la fracción de eyección. Este trabajo evalúa la alteración del sodio y potasio en pacientes hospitalizados por este síndrome. Se revisaron las historias de pacientes con insuficiencia cardíaca ingresados al servicio de Cardiología, registrando datos en base a un protocolo. Se revisaron 33 historias de las cuales 11 pacientes eran mujeres y 22 eran hombres, con un promedio de edad de 72,64 y 71,52 años respectivamente. Días de hospitalización promedio de 14,91 días. Todos los pacientes tenían dieta hiposódica excepto uno debido a diarrea. El 57,6% tenían una sola patología y el resto dos o tres. La hipertensión arterial es la patología más frecuente en un 81,8%, seguido de cardiopatía isquémica en un 30,3%. Recibieron tres diuréticos (furosemida, espirolactona, hidroclorotiazida) el 48,5% de los pacientes y dos diuréticos el 48,5%. El 51,5% de los pacientes tenían potasio bajo y el 57,6% sodio bajo. En un 50% de los pacientes se encuentra que el potasio y sodio están bajos que se relaciona con el uso de diuréticos y una dieta hiposódica. Habría que considerar el uso de suplemento de potasio en estos casos.

Heart failure a syndrome caused by multiple factors engenders a process of ventricular remodeling. It is an enormous public health problem, with an increasing number of hospitalizations. Diuretics, still useful for treatment, produce electrolyte abnormalities can cause arrhythmias, worsening heart failure and larger reduction in the ejection fraction. This study evaluated the alteration of sodium and potassium levels in patients hospitalized with this syndrome. We reviewed the charts of patients with heart failure admitted to the cardiology service, recording data with the use of a standardized form. We reviewed 33 records for 11 women and 22 men with a mean age of 72.64 and 71.52 years respectively. The average number of days of hospitalization was 14.91 days. All patients had a low sodium diet except one because of diarrhea. A single pathology was present in 57.6% with the rest having two or three. Hypertensión was the most frequent pathology in 81.8% , followed by ischemic heart disease in 30.3%. Three diuretics (furosemide, spironolactone, hydrochlorothiazide) were used in 48.5% of patients and two diuretics in 48.5%. In 51.5 of patients there was low potassium and in 57.6% low sodium. Potassium and sodium were low in 50% of patients, which was associated with the use of diuretics and a low salt diet. Potassium supplements should be considered in these cases.

Simultaneous spectrophotometric estimation of bisoprolol fumarate and hydrochlorothiazide in tablet dosage form

Two analytical methods have been developed for simultaneous quantification of bisoprolol fumarate and hydrochlorothiazide in combined pharmaceutical dosage form using spectrophotometer. Excellent simplicity, accuracy, precision and economy were achieved by the assay. The 'method I' was based upon 'simultaneous equations' whereas the 'method II' was based upon 'multicomponent mode of analysis' of the instrument. For both these methods, 0.1 N NaOH was used as solvent. In this solvent, bisoprolol fumarate showed absorbance at 224 nm and hydrochlorothiazide at 273 nm. Linearity lies in the concentration range of 3 - 21 microg/ml for bisoprolol fumarate and 3 - 18 microg/ml for hydrochlorothiazide. The methods were validated statistically and by recovery studies

Assessment of efficacy, safety and tolerability of fixed dose combination of telmisartan 40mg and hydrochlorothiazide 12.5mg in adult Indian patients with mild to moderate hypertension.

The objective of the study was to assess the efficacy, safety and tolerability of a fixed dose combination of telmisartan 40 mg and hydrochlorothiazide 12.5 mg in adult Indian patients with mild to moderate hypertension. A prospective, multicentric, open-label, non-comparative, phase IV study was conducted. A total of 353 patients of either sex, between 18- 65 years of age with supine blood pressure (BP) levels of systolic BP (SBP) of 140-200 mmHg and diastolic BP (DBP) of 95-114 mmHg were included. After a placebo run-in period of 2 weeks, each patient received a fixed dose combination of telmisartan/hydrochlorothiazide (40mg/12.5mg) once daily, for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety were assessed by physical examination, laboratory parameters and evaluation of adverse events. A total of 339 patients completed the study with 14 drop-out cases because of loss to follow-up. There was a significant fall (p<0.05) in both the SBP and DBP starting from the second week as compared to the baseline. Mean SBP had a significant reduction of 23.55 mmHg (15.0%) and 27.79 mmHg (18%) at the end of 6th and 8th week respectively, compared to baseline values. Mean DBP had also had a significant reduction of 12.51 mmHg (12.6%) and 15.17 mmHg (15.3%) at the end of 6th and 8th week respectively, compared to baseline values. This combination was well tolerated with only 3.9% of the total cases reporting mild adverse events like fatigue, dizziness, nausea, diarrhoea etc. The laboratory values were within normal limits. Fixed dose combination of telmisartan/hydrochlorothiazide (40 mg/12.5 mg) once daily has a significant therapeutic effect and a good tolerability profile in adult Indian patients with mild to moderate hypertension.

Hipertensión pulmonar e infección por VIH: comunicación de un caso / Pulmonary hypertension and HIV infection: 1 case report

Pulmonary hypertension associated to HIV infection has been reported in the literature with increased frequency. Apparently, this condition has a faster clinical evolution and a higher mortality than primary pulmonary hypertension. The pathogenic mechanisms of HIV associated pulmonary hypertension and the influence of its treatment on patientÕs evolution are not well known. We report a 32 years old homosexual male that developed a severe dyspnea in a period of 2 months. Echocardiogram demonstrated right ventricular dilatation and a systolic pulmonary artery pressure of 86 mm Hg. No other causes for pulmonary hypertension were found. Antiviral therapy and vasodilator treatment with a calcium channel blocker were started and the patient had an important subjective clinical improvement

Comparación de la eficacia antihipertensiva de monoterapia en dosis crecientes versus terapia asociada en bajas dosis / Comparison of increasing doses of a single drug or combination medications in the treatment of hypertension

Background: When hypertension treatment does not achieve the expected reduction in blood pressure levels, experts recommend increasing the dose of the initially used drug or the addition of a new medication. Aim: To compare the efficacy of increasing doses of losartan or the addition of hydrochlorothiazide to achieve adequate blood pressure levels in patients with hypertension. Patients and methods: Seventy three patients aged 64.4 ñ 5.3 years, with stage 1 or 2 essential hypertension were studied. If after four weeks of treatment with losartan 50 mg od, blood pressure levels were still high, the dose was increased to 100 mg od. After four weeks with this new schedule, the treatment was switched to losartan 50 mg and hydrochlorothiazide 12.5 mg for another four weeks. Results: Thirty seven patients normalized blood pressure with losartan 50 mg od. Of the 36 patients that did not respond, 69 percent achieved a normal blood pressure with losartan 100 mg od and 81 percent did so with the combination of losartan and hydrochlorothiazide. Combination therapy resulted in a better blood pressure lowering than monotherapy (33.2 ñ 3.2 and 29.5 ñ 3.4 mm Hg for systolic blood pressure respectively, 16.4 ñ 3.2 and 13.2 ñ 3.4 mm Hg for diastolic blood pressure, p <0.05). No changes in blood glucose, total and HDL cholesterol, triglycerides, urea nitrogen and uric acid were observed with the combination therapy. Conclusions: In this group of patients, combination therapy achieved better blood pressure levels than monotherapy in high doses

Captopril associado a didroclorotiazida no tratamento da hipertensäo leve e moderada / Association of captopril and hydrochlorothiazide in mild and moderate hypertension. A Brazilian multicenter study

Objetivo - Avaliar a eficácia e tolerabilidade da associação de captopril 50mg com hidrocloratiazida 25 mg em hipertensos com pressão arterial diastólica (PAD) entre 95 e 115mmHg. Métodos - Estudo aberto, multicêntrico, não comparativo. Na fase inicial, durante 2 semanas, os pacientes receberam placebo, seguida de ½ comprimido da associação. Os pacientes foram avaliados após 4,8 e 12 semanas. Após 8 semanas de tratamento, naqueles em que a PAD foi >90mmHg, foi prescrito um comprimido/dia. Resultados - Foram analisados 433 pacientes, com idades de 47+10 anos, sendo 30 por cento mulheres e 76 por cento brancos. As pressões sistólica/diastólica iniciais foram de 156+16/103+11 mmHg, após 14 dias de placebo, 156+15/103+9 mmHg (p>0,05) e, após 4,8 e 12 semanas, mostraram progressiva redução (p<0,05) para 143+14/95+11, 140+13/91+9 e 134+11/86+8 mmHg. O controle pressórico foi observado em 45, 67 e 88 por cento (p<0,05), após 4,8 e 12 semanas. Tosse foi o sintoma mais importante registrado em 7 por cento dos pacientes em placebo e 12 por cento nos que usavam a associação. A tolerabilidade foi considerada boa por 98 por cento dos pacientes. Conclusão - A associação de captopril com hidroclotiazida é eficaz e tem boa tolerabilidade, sendo prescrita em dose única diária em monoterapia, para hipertensos leves e moderados.

Efecto de la inhibición de enzima convertidora de antagonista de angiotensina con perindopril sobre la hipertrofia ventricular izquierda en pacientes hipertensos / Effect of ACE inhibition using perindopril upon left ventricular hypertrophy in hypertensive patients

La regresión de hipertrofia ventricular izquierda (HVI) en pacientes hipertensos podría tener beneficios clínicos en la historia natural de estos pacientes. En el presente estudio hemos evaluado prospectivamente y en forma abierta el efecto del inhibidor de la enzima convertidora de angiotensina perindopril (Per) (adicionando hidrocloratiazida cuando no se pudo controlar la presión arterial) sobre la masa ventricular izquierda (MVI) medida ecográficamente (fórmula de Devereux). Se estudiaron 19 pacientes hipertensos esenciales (PA promedio 165 ñ 4/99 ñ 3 mmHg, promedio ñ ES) con HVI (10 hombres, 9 mujeres, edad promedio 57,7 ñ 8.9 años, índice de masa corporal 29,3 ñ 3,6 m/kg²) antes y después de 3, 6 y 12 meses de tratamiento. Dieciocho pacientes (95 por ciento) recibieron 8 mg/día de Per y 17 pacientes requirieron la adición de Hctz (dosis promedio 26 ñ 2 mg/día). Con el tratamiento se obtuvo un descenso significativo de las presiones arteriales aisladas (140 ñ 2/86 ñ 2 mmHg) y en la monitoría ambulatoria de 24 horas. No se observaron variaciones significativas en el peso corporal y tampoco en ninguno de los parámetros evaluados a lo largo del estudio (potasio plasmático, creatinina, glicemia, hematocrito, colesterol). Con el tratamiento se observó disminución significativa de la dimensión diastólica (F = 3,5 p < 0,03) y del grosor de la pared posterior del VI (F = 7,69, p < 0,001) a contar de los 6 meses de tratamiento y de la aurícula izquierda a partir de los 3 meses (F 5,62, p < 0,03). No se observaron cambios en la dimensión sistólica, grosor del septum interventricular, fracción de acortamiento, velocidades de las ondas E y A ni en la relación E/A de llenado diastólico transmitral. La masa ventricular y el índice de masa ventricular izquierda se redujeron significativamente (F = 7,04,p < 0,001 y F = 6,2, p < 0,01, respectivamente) alcanzando al final del estudio un 82 por ciento de la masa ventricular inicial. El descenso de la MVI y del IMVI se correlacionó significativamente con disminución de la PA sistólica y diastólica, de la PA media y diastólica nocturna. En conclusión: el control de la presión arterial con perindopril, asociado en la mayoría de los casos a hidroclorotiazida en dosis bajas logró inducir regresión de la HVI a partir de los 6 meses de tratamiento con disminución tanto del volumen diastólico como del grosor de la pared libre del VI

Regresión de hipertrofia ventricular izquierda con isradipino en pacientes hipertensos / Regression of left ventricular hypertrophy with isradipine in hypertensive patients

La hipertrofia ventricular izquierda (HVI) es un factor de riesgo cardiovascular importante, frecuentemente asociado a hipertensión arterial (HTA). Su regresión en estos paciem¿ntes podría asociarse a beneficios en la historia natural de la enfermedad hipertensiva, lo que pareciera depender en alguna medida del control de las cifras de presión arterial. La eficacia en inducir regresión de HVI en seres humanos pudiera ser diferente según el tipo de fármaco antihipertensivo. Hemos evaluado la hipótesis de isradipino, un antagonista del calcio con marcada selectividad vascular, en dosis normotensantes induce regresión de HVI en nuestros pacientes hipertensos que presentan HVI. 19 pacientes (edad promedio 59 años, 9 mujeres) con HTA esencial e HVI (séptum + pared posterior VIò 23 mm) comenzaron a ser tratados con isradipino (Dynacirc SROr) y 18 pacientes completaron 12 meses con una sola dosis diaria matinal normotensante (promedio final 16,4 ñ 3,3 mg/día). En 7 pacientes se complementó con una dosis baja de hidroclorotiazida y triamterene con objeto de mantener cifras tensionales normales. Se realizó ecocardiograma basal, a los 3, 6 y 12 meses de tratamiento, midiéndose séptum VI (sp,mm), pared posterior de VI (pp,mm) y dimensión diastólica (DD,mm), con lo que se calculó la masa ventricular VI. Además de la normotensión mantenida se observó una disminución significativa, a contar del tercer mes de tratamiento de los grosores del sp,pp y diámetros de la cavidad VI, así como de la masa VI, la que alcanzó a los 12 meses un 81 por ciento de la masa inicial del VI. No hubo modificaciones de la función ventricular ni de la frecuencia cardíaca. Tampoco se modificó la función renal. En conclusión, estos resultados demuestran que isradipino, en una sola dosis diaria normotensante, es capaz de inducir regresión significativa de HVI en pacientes con HTA. Esta regresión está dad por disminución tanto del grosor de las paredes como de las dimensiones del VI y comenzó a observarse desde los 3 meses de tratamiento

Efficacy and acceptability of perindopril in essential hypertension.

The clinical efficacy and acceptability of once-daily perindopril (4 to 8 mg) monotherapy and in combination with hydrochlorothiazide (50 mg/day) was studied in mild to moderate stable essential hypertensive patients in 4 centres in Thailand. After 2-4 weeks of placebo run-in period, patients received active treatment for 3 months starting with 4 mg perindopril once daily. Dose titration was at second and third month of active treatment if the supine DBP was > 90 mmHg. The dose was doubled and if necessary, 50 mg/day hydrochlorothiazide was added in the last month. The results in 95 patients showed that the mean reduction in supine SBP/DBP at 1, 2 and 3 months of treatment was 10.3/8.0, 13.2/8.7 and 19.1/13.7 mmHg respectively. At the end of the study, 80 per cent of the patients showed normalisation of the supine diastolic blood pressure (supine DBP < or = 90 mmHg) with 30 per cent receiving combined therapy of perindopril and hydrochlorothiazide. There was no significant change in routine haematology or serum biochemistry except for slight increase of potassium levels in patients receiving 8 mg perindopril monotherapy. The incidence of side effects and withdrawal from treatment were quite low. Cough was the major side effect reported comprising 13.6 per cent with only 1 case withdrawn. The study confirms the previous studies that perindopril had satisfactory antihypertensive efficacy and acceptability profiles.

Tratamento da hipertensäo arterial leve e moderada com o uso de captopril associado à hidroclorotiazida em pacientes näo-responsivos à diureticoterapia isolada / Treatment of mild and moderate hypertension with captopril associated with hydrochlorothiazide in not responsive patients to single diuretic therapy

O objetivo deste ensaio clínico foi estabelecer a eficácia do tratamento com o captopril em baixa dosagem para o tratamento da hipertensäo arterial discreta e moderada. Foram admitidos pacientes hipertensos cuja pressäo arterial (PA) näo foi normalizada pelo uso isolado da hidroclorotiazida. A dose de captopril usada inicialmente foi de 12,5 mg, duas vezes ao dia, e a hidroclorotiazida foi usada na dose de 25 mg/dia durante 30 dias. Quando a PA näo teve reduçäo para valores normais ou näo apresentou reduçäo de ao menos 10%, os pacientes foram submetidos a um aumento da dose de captopril para 25 mg, duas vezes ao dia, com manutençäo da dose de 25 mg de hidroclorotiazida. Isto ocorreu em 31,9% dos casos. Os pacientes que näo responderam a esse esquema posológico (12,6% dos casos) foram mantidos com a mesma dose de captopril (25 mg duas vezes ao dia), aumentando-se a hidroclorotiazida para 50 mg/dia, durante um período adicional de 30 dias, até a avaliaçäo final. Ao final de três meses de tratamento foram obtidos os seguintes resultados: 3.081 pacientes (86,4%) apresentaram normalizaçäo da PA (diastólica < ou = 90 mmHg), 200 pacientes (5,6%) apresentaram reduçäo da PA, porém näo atingiram os valores normais e 285 pacientes (8,0%) näo responderam ao esquema do estudo. A pequena incidência de efeitos colaterais (9,9%) foi desprovida de significância clínica, sendo que 87% dos pacientes referiram melhor qualidade de vida

Avaliaçäo do efeito anti-hipertensivo da combinaçäo do maleato de enalapril e hidroclorotiazida em baixas doses / Evaluation of antihypertensive effect of enalapril maleate and hydrochlorothiazide combination in low dosages

Em ensaio clínico aberto, aleatório, comparativo, foram estudados 42 pacientes adultos, portadores de hipertensäo arterial essencial (HAE) (pressäo diastólica supina [PDS] > 90mmHg e < 114mmHg), com idade média de 48,6 anos, sendo nove homens (21,4%) e 33 mulheres (78,6%); 27 brancos (64,3%) e 15 negros (35,7%). O período inicial de observaçäo foi de quatro semanas (sem tratamento anti-hipertensivo, sob uso de placebo - um comprimido ao dia) e a dose única diária de enalapril foi de 20mg nas seis semanas seguintes, findas as quais, os pacientes näo responsivos eram "randomizados" para acrescentar hidroclorotiazida 12,5mg (grupo A) ou 25mg ou 50mg (grupo B) aos 20mg iniciais de enalapril por mais seis semanas. Os pacientes eram reavaliados clinicamente a cada duas semanas com controle da pressäo arterial (PA) freqüência cardíaca (FC) e peso corpóreo (P). A evoluçäo da PA mostrou queda no grupo A de 156 x 101 para 140 x 91mmHg e no grupo B 155 x 102 para 138 x 91mmHg. Normalizaçäo da PA ocorreu em 18 pacientes (66,7%) do grupo A e em oito pacientes (53,3%) do grupo B. Nos parâmetros laboratoriais avaliados (leucometria, uréia plasmática e calemia) näo houve variaçäo significativa ao longo do estudo. Durante o período de tratamento ativo, näo foram observadas reaçöes adversas. Na populaçäo estudada, näo ocorreram sintomas ou alteraçöes laboratoriais clinicamente significativos em nenhum dos grupos. Os autores concluem que o efeito anti-hipertensivo produzido pela combinaçäo de enalapril 20mg e hidroclorotiazida 12,5mg näo diferiu significativamente daquele proporcionado pela associaçäo da mesma dose do inibidor da enzima de conversäo com doses maiores de diurético