Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease.

BACKGROUND: Atherosclerotic renovascular disease (ARD) coexists with arterial obstructive disease in the coronary, cerebral, and peripheral arteries that may remain underdiagnosed and untreated. METHODS: This retrospective study compares overall survival and renal survival (i.e., time to doubling of serum creatinine or end-stage renal disease (ESRD)) over an 11-year period in 104 ARD patients of whom 68 received statin therapy (group S) because of elevated lipid levels and 36 had no statin (group NS) because of normal lipid profile at entry. RESULTS: Atherosclerosis in another vascular bed was documented in 84%. Lipid profiles at end point were virtually identical in both the groups. Group S had mean survival 123months (confidence interval (CI) 113-134) with four deaths, and mean renal survival 122months (CI 113-131). Group NS had mean survival 33 months (CI 23-42) with 13 deaths, and mean renal survival 27 months (CI 17-37). CONCLUSIONS: Statin therapy was associated with lesser rate of progression of renal insufficiency (with 7.4% of S patients reaching renal end points vs. 38.9% of NS patients) and lower overall mortality (5.9 % in S vs. 36.1% in NS patients), P < 0.001 for both. Although both groups received what was deemed optimal therapy, they did have other differences that may have affected the outcomes (a limitation addressed by Cox multiple regression analysis). These results suggest the need for prospective randomized controlled studies in ARD patients in order to explore potential benefits of statins that may not be attributable solely to lipid lowering.

Efficacy and tolerability of the combination valsartan/hydrochlorothiazide compared with amlodipine in a mild-to-moderately hypertensive Brazilian population.

Most hypertensive patients need more than one drug to reach recommended blood-pressure targets. We investigated the effects on 24-h ambulatory blood pressure (ABP) of the angiotensin-receptor blocker, valsartan, in combination with hydrochlorothiazide (HCTZ), compared with the calcium-channel blocker amlodipine in a Brazilian population in a multicentre, double-blind, double-dummy, parallel group, controlled study in 373 patients with essential hypertension. After a 2-week washout period, patients with a mean sitting systolic blood pressure (SBP) of 160-190 mmHg were randomized to receive either valsartan 160 mg o.d., or amlodipine 5 mg o.d. for 2 weeks and subsequently force-titrated to valsartan 160 mg/HCTZ 25 mg o.d. or amlodipine 10 mg o.d. This regimen was continued until the end of the study at week 8. The primary efficacy parameter was the change from baseline to week 8 in mean 24-h SBP. Secondary endpoints were change in mean 24-h diastolic blood pressure (DBP), tolerability and safety of treatments. Valsartan/HCTZ achieved a mean reduction in systolic ABP of -19.1 +/- 11.3 mmHg compared with -20.7 +/- 12.0 mmHg with amlodipine (p = 0.324 for the comparison) and in diastolic ABP by -11.1 +/- 7.4 mmHg vs -11.6 +/- 7.2 mmHg by amlodipine (p = 0.853 for the comparison). The valsartan/HCTZ group exhibited markedly lower rates of adverse events and discontinuations than the amlodipine group. Peripheral oedemas were far more frequent with amlodipine than with valsartan/ HCTZ (1.6% with valsartan/HCTZ; 16.8% with amlodipine). Thus, the valsartan 160 mg/HCTZ 25 mg combination appears to be as efficacious as amlodipine 10 mg in this patient population but better tolerated.

Crise hipertensiva: definição, epidemiologia e abordagem diagnóstica / Hypertensive crisis: definition, epidemiology and diagnosis

Crise hipertensiva designa uma condição de elevação rápida e sintomática da pressão arterial com risco de deterioração de órgão-alvo ou de vida em potencial. Constitui na emergência clínica mais freqüente nos prontos-socorros e podem exigir ação rápida com necessidade de internação em terapia intensiva no caso de emergência hipertensiva. Na maioria das vezes, a lesão em órgão nobre pode ser mais importante que o nível da pressão arterial. É complicação que reflete a precariedade do tratamento crônico da hipertensão e acomete populações menos favorecidas, de baixa renda e escolaridade e atendimento primário ineficaz. O exame de fundo de olho é fundamental para estabelecer o diagnóstico. O controle crônico da pressão arterial é o melhor método para diminuir a incidência de urgências e emergências hipertensivas.

Avaliaçäo da eficácia da lercanidipina comparada à nifedipina oros no tratamento da hipertensäo arterial primária leve e moderada pela monitorizaçäo ambulatorial de 24 horas (MAPA) / Evaluation of efficacy of lercanidipine compared to nifedipine oros in treatment of mild and moderate primary arterial hypertension by ambulatorial 24 hours monitoring

A eficácia anti-hipertensiva da lercanidipina foi avaliada de forma comparativa e simples-cega com a nifedipina oros no tratamento da hipertensão primária leve a moderada nas 24 horas. Empregou-se a monitorização ambulatorial da pressão arterial nas 24 horas (MAPA) em 18 pacientes hipertensos leves a moderados, de ambos os sexos, sendo que a metade recebeu lercanidipina 10 mg/dia e os demais nifedipina oros 30 mg por 4 semanas. Os pacientes que não apresentaram a pressão arterial (PA) normalizada, sendo o critério PAS > 140 mmHg e/ou PAD > 90 mmHg, tiveram a dose duplicada; nos demais pacientes foi mantida e todos foram acompanhados por mais 4 semanas. Foi realizada a MAPA de 24 horas antes e após a primeira dose de cada medicação, ao final das 8 semanas do estudo e após 48 horas da administração da última dose da lercanidipina ou nifedipina oros. Foram observadas reduções semelhantes da PA nos dois grupos em todos os momentos durante a MAPA após a primeira dose e ao final das 8 semanas de tratamento durante as 48 horas após a última tomada. A persistência do efeito anti-hipertensivo 48 horas após a última dose foi mantida sem diferença quando se comparou os dois fármacos. A eficácia anti-hipertensiva da lercanidipina foi semelhante à da nifedipina oros nos hipertensos primários leves a moderados nas 24 horas, havendo persistência do efeito anti-hipertensivo, verificado com ambas as drogas durante o tratamento crônico, por um período de até 48 horas após a última tomada.

Avaliaçäo da eficácia anti-hipertensiva e tolerabilidade de monoterapia com lisinopril em hipertensos leves e moderados / Evaluation of antihypertensive efficacy and tolerability of lisinopril in mild and moderate hypertensive patients

Avaliar a tolerabilidade e a eficácia de Lisinopril através da medida casual da pressäo arterial e da MAPA. Estudo aberto, multicêntrico, näo comparativo envolvendo 69 hipertensos com pressäo arterial distólica entre 90 e 114 mmHg após 2 semanas iniciais de placebo. A fase seguinte constou de 7 visitas consecutivas (14, 28, 42, 70, 98, 126 e 154 dias) após a introduçäo de Lisinopril 10, 20 ou 40 mg/dia. Nas visitas V0 e V7 foram feitos: MAPA, exames bioquímicos e ecocardiograma. Em todas as visitas a medida da pressäo arterial foi feita em posiçäo supina e ereta. A idade média foi de 49+11 anos, com 67 por cento de mulheres. A pressäo arterial supina ao final do placebo (VO) foi de 157+15/102+7 mmHg. Em V2 a pressäo arterial supina foi de 144+17/89+10; em V4=134+16/85+8 mmHg p<0,0001 (VO>VI>V2>(V3=V4=V5=V6=V7). As pressöes obtidas com a MAPA foram inferiores (p<0,05) na V7 em relaçäo à V0. Em relaçäo ao controle pressórico (diastólica inferior a 90 mmHg), 49 por cento obtiveram-no em VI e 81 por cento alcançaram-no em V4. Em V7, 88 por cento dos pacientes tinham tido reduçöes da diastólica maiores de 10 mmHg. A tolerabilidade avaliada pelos pesquisadores foi considerada boa para 81 por cento dos pacientes, e insatisfatório para 6 por cento. Aproximadamente 5 por cento dos pacientes apresentaram tosse e foram excluídos. A terapêutica com Lisinopril em dose única diária mostrou-se eficaz no controle da pressäo arterial e a tolerabilidade foi considerada boa.

Estudo comparativo duplo-cego da eficácia e segurança do cilazapril comparadas à nifedipina "retard" no tratamento da hipertensäo arterial leve e moderada / Double-Blind Comparative Study of Efficacy and Safety of Cilazapril Compared to Nifedipine Retard in the Treatment of Mild and Moderate Hypertension

PURPOSE--To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. METHODS--forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmHg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. RESULTS--The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 +/- 14/103 +/- 5 - nifedipine 157 +/- 17/108 +/- 7mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 +/- 9 - nifedipine 96 +/- 11mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no difference inter groups. BP normalization was obtained in 58 per cent of the patients with cilazapril and in 61 per cent in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16 per cent) patients of the cilazapril and 15 (39per cent) of nifedipine related collateral events, although no difference were observed between groups. CONCLUSION--Cilazapril 2.5 to 25mg normalized BP in 58 per cent of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects

Estudo aberto comparativo captopril + hidroclorotiazida versus clortalidona para tratamento da hipertensäo primária leve e moderada / An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension

Objetivo - Comparar o efeito anti-hipertensivo e alterações metabólicas da associação captopril + hidroclorotiazida (C+HCTZ) contra clortalidona (CT) para tratamento de hipertensão arterial primária leve e moderada. Métodos - cinqüenta e cinco pacientes que tiveram a sua medicação anti-hipertensiva suspensa por 15 dias ou sem tratamento prévio, foram randomizados para tratamentos com a associação captopril 50mg + hidroclorotiazida 25mg (n=29) ou clortalidona 50mg (n=26). A avaliação clínica foi realizada previamente à medicação e mensalmente durante 3 meses e os exames laboratoriais foram feitos no início e ao final do estudo. Resultados - A pressão arterial (PA) no período placebo não foi diferente entre os grupos (C+CHTZ: 161 ± 25/102 ± 6 - CT: 155 ± 18/101 ± 6 mmHg), porém a diminuição da pressão diastólica já no 1° mês foi estatisticamente significante no grupo C+HCTZ (89±8 mmHg) comparado ao grupo CT (94±8 mmHg, p<0,05). O perceptual de queda da PA diastólica em média, de 12% no grupo C+HCTZ e no grupo CT variou de 7 (1° e 2° mês) a 11% (3° mês). Embora sem diferença estatística, obteve-se normalização pressórica em 69% dos pacientes com captopril associado ao diurético e, em 50%, com clortalidona. Observou-se uma redução significativa da potassemia com clortalidona (4,2±0,7 para 3,7±0,4 mEq/L, p<0,01) e manutenção dos níveis de potássio com associação captopril e tiazídico. Este último tratamento também reduziu significativamente os níveis de colesterol (219±39 mg/dl para 202±39 mg/dl, p<0,04). Conclusão - Os resultados mostraram que a associação de captopril com dose baixa de tiazídico normaliza a PA em 69% de pacientes portadores de hipertensão arterial primária leve e moderada e age mais rapidamente que a clortalidona no controle pressórico, apresentando efeito metabólico benéfico de reduzir os níveis de colesterol sem alterar a potassemia

Purpose - To compara the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. Methods - Fifty five patients, whithout treatment or treated with 15 days placebo were randomized for treatment with the combination of captopril 50mg and hydrochlorothiazide 25mg (n=29) against chlorthalidone (n=26). The clinical evaluation was done during placebo and monthly throughout three months, and the laboratory tests were done before and at the end of the study. Results - The blood pressure were similar between groups during placebo period (C+HCTZ: 161±25/102±6 - CT: 155±18/101±6 mmHg); the diastolic blood pressure decreases significantly at first month already in the group C+HCTZ (89±8 mmHg) comparad to group CT (94±8 mmHg, p<0,05). The percentile diastolic and mean blood pressure dropped, in average, 12% in C+HCTZ group and in CT varied between 7 (1st and 2nd month) to 11% (3rd month). Without statistical difference, the blood pressure normalization was obtained in 69% of the patients with the association captopril and diuretic and in 50% of the patients in the chlorthalidone group. It was observed a significant reduction of potassium in patients treated with chlorthalidone (4,2±0,7 to 3,7±0,4 mEq/L, p<0,01) that was not observed with the captopril and the thyazide associated. The last treatment also significantly reduced the cholesterol levels (219±39mg/dl to 202±39mg/dl, p<0,04). Conclusion - Our results indicate that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. In addition has metabolic benefits reducing cholesterol levels with no alteration in potassium levels

Captopril na hipertensão arterial leve e moderada resistente a diurético: valor preditivo da eficácia através do teste agudo do captopril / Captopril in mild and moderate arterial hypertension diuretic resistant: acute captopril test to predict treatment efficacy

Objetivo - Estabelecer se a resposta aguda ao captopril pode ser aplicada como teste preditivo de eficácia a longo prazo, no tratamento da hipertensäo arterial de pacientes que näo obtiveram o controle pressórico com diurético. Métodos - Foram estudados 120 pacientes portadores de hipertensäo arterial leve e moderada, näo controlada com 100 mg de hidroclorotiazida. Determinaram-se as variaçöes da pressäo arterial sistólica (PAS), diastólica (PAD) e média durante a administraçäo aguda e crônica do captopril. Procurou-se correlacionar o percentual de queda destas pressöes, obtidas ao final do tratamento, com aquelas obtidas com o teste de captopril, aplicando-se a funçäo discriminante linear (FDL) e o teste do Qui-quadrado com índices preditivos de tratamento. Previamente à aplicaçäo destes testes, subdividiram-se os pacientes em dois grupos de acordo com o percentual de queda da pressäo arterial média )PAM) em grupo de mau desempenho (G1) ou bom desempenho (G2) caso a PAM, respectivamente, apresentasse queda menor ou igual/maior a 159% ao final do tratamento com a associaçäo do diurético e captopril. Resultados - Os autores médios da pressäo arterial durante o período placebo foram 168 ñ 2/109 ñ 1 mmHg. Apos o uso do diurético e a associaçäo com captopril os valores da pressäo arterial foram 151 ñ 1/101 ñ 1 e 137 ñ 1/90 ñ 1 mmHg, respectivamente, valores significativamente diferentes entre si (p < 0,05). A normalizaçäo dos valores pressóricos foi observada em 58% dos pacientes. A FDL calculada apresenta a seguinte equaçäo: FDL = 7,92 queda % PAS + 1,21 queda % PAD. O valor médio para FDL de G1 foi de 192 e para G2 de 361. O valor 276 representa o ponto médio de separaçäo dos dois grupos. Aplicando-se a FDL e o qui-quadrado, as percentagens de acerto para G1 foram, repectivamente, de 80% e 47%. Para o grupo G2, de bom desempenho, a FDL e o qui-quadrado estäo de acordo, respectivamente, em 72 e 77%. Conclusäo - O emprego da funçäo discriminante linear e do qui-quadrado sugerem que o teste do captopril pode ser metodologia auxiliar para selecionar pacientes que näo foram controlados com diuréticos, e que iräo ter benefício com a adiçäo de um inibidor da enzima conversora ao tratamento

Purpose - To evaluate if acute blood pressure response with captopril can be applied as a predictive test of treatment efficacy in hypertensive patients uncontrolled with large dose of diuretics. Methods - Mild and moderate 120 uncontrolled hypertensive patients treated with hydrochlorothiacide 100 mg, were submitted to captopril (25 mg) test. The systolic (SBP) and diastolic (DBP) blood pressure acute and chronic responses were correlated and the linear discriminate function (LDF) and qui-square were applied to test the treatment efficacy. Previously two groups (G) patients were obtained as bad responders (G1) and good responders (G2) respectively, if the mean arterial pressure fall less or equal/more than 15% at the end of the associated treatment with diuretic and captopril. Results - Mean arterial pressure values during placebo were 168 ± 2/109 ± 1 mmHg. This values after diuretic and associated captopril treatment were, respectively, 151 ± 1/ 101 ± 1 and 137 ± 1/90 ± 1 mmHg, all signif cant different (p < 0.05). Blood pressure normalization was obtained in 58% of patients. The calculated LDF formula were: LDF = 7.92 ­ % SBP ± 1.21 D % DBP. The G1 LDF mean value was 192 and 361 to G2. The value 276 represents the separation medium point between both groups. As far the distance from the separation medium point for a calculated LDF for a calculated LDF for a problematic patient, as more will be the probability for this patient to belong to tLis group. LDF and qui-square classified correctly, respectively, 80% and 47% of patients in G1. To G2 good re ponders patients, LDF and qui-square agreed, respectively, in 72 and 77%. Conclusion - The results obtained suggest that captopril test, could be useful as an auxiliary methodology to select hypertensive patients, uncontrolled with diuretic treatment, which might benefit with the association of converting enzyme inhibitors drugs

Captopril na hipertensão arterial leve e moderada resistente a diureticoterapia: estudo multicêntrico / Captopril for the treatment of mild to moderate hypertension diuretic resistant multicenter study

Objetivo - Avaliar o efeito antihipertensivo do captopril para o tratamento de hipertensäo arterial leve e moderada resistente a diurético-terapia. Métodos - Hipertensos leves e moderados, sem, ou que tiveram a medicaçäo antihipertensiva suspensa por sete dias, foram tratados com 50 mg de hidroclorotiazida por duas semanas. Os pacientes que obtiveram normalizaçäo pressórica (pressäo arterial diastólica * 90 mmHg) foram excluídos, e nos demais, a dose do diurético foi aumentada para 100 mg; por mais três semanas. Nos hipertensos em que este tratamento näo teve sucesso para normalizar a pressäo arterial (n = 120), captopril, na dose de 25 a 50 mg/dia, em duas tomadas diárias, foi introduzido durante nove semanas. Após este período, a um subgrupo (n = 74) de pacientes a dose necessária de captopril foi administrada com o diurético em uma única tomada, por mais três semanas adicionais. A avaliaçäo clínica foi realizada previamente ao diurético, a cada duas semanas após sua introduçäo e a cada três, durante o captopril Os exames laboratoriais foram analisados antes do diurético, antes da introduçäo do captopril e ao final de 12 semanas do tratamento combinado. Resultados - A pressäo arterial supina no período placebo que foi de 168 ñ 2 / 109 ñ 1 mmHg apresentou um decréscimo significante com o tratamento diurético para 151 ñ 1 / 101 ñ 1 mmHg e uma queda adicional para 137 ñ 1 / 90 ñ 1 mmHg com a associaçäo do captopril na dose média de 44 ñ 1 mg. Na 12ª semana de tratamento quando o paciente estava medicado com dose única diária há 3 semanas a pressäo arterial foi de 137 ñ 2 / 90 ñ 1 mmHg. Obteve-se normalizaçäo pressórica em 58% dos pacientes com o captopril em duas tomadas e em 63% com dose única. Obteve-se normalizaçäo pressórica em 63% dos pacientes näo brancos e em 56% dos pacientes com idade superior a 45 anos. Houve alteraçäo significante dos níveis plasmáticos de potássio com o diurético que näo reverteu com a associaçäo de captopril. Conclusäo - O captopril em baixa dose administrado uma ou duas vezes ao dia causou queda pressórica adicional em pacientes portadores de hipertensäo arterial e moderada resistente a diureticoterapia

Purpose - To evaluate the antihypertensive effect of captopril in mild and moderate hypertensive patients uncontrolled with diuretics. Methods - Low dose of captoprzl (25 to 50 mg) bid were associated during 9 weeks in 120 patients previously treated with 100 mg of hydrochlorothiazid e. A subgroup of patients (74) were followed additionally for 3 weeks with the same dose of the drugs administered as a single dose. The patients were clinically evaluated after two weeks placebo, and each three weeks of active drugs. Blood pressure normalization were considered when diastolic arterial pressure was < 90 mmHg. Laboratory tests were measured before diuretic, before captopril and at the end of combined twelve weeks treatment. Results - After 15 days washout, the baseline supine arterial pressure, 168 + 2/109 + 1 mmHg decrease significantly-with diuretic to 151 + 1 / 101 + 1 mmHg and the drop wasfurther increased with captopril b.i.d., with a mean dose of 44 + 1 mg, to 137+ 1/90 + 1 mmHg. Blood pressure normalization was obtained in 58% patients with captopril b.i.d. and in 63% as single dose. Blood pressure normalization was achieved in 63% of non-white patients and in 56% patients over 45 years old. Plasmatic potassium decreased significantly with diuretic and did not recovered when captopril was associated. Conclusion - Our results indicate that the addition of low dose of captopril twice or once a day may result in a marked additional blood pressure reduction in cases of insuficient control by the diuretic alone