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.

Perfil lipídico e risco cardiovascular em Amazônidas / Lipid profile and cardiovascular risk in two Amazonian populations

OBJECTIVE: To compare the lipid profiles and coronary heart disease risks of 2 Brazilian Amazonian populations as follows: a riverside population (village of Vigia) and an urban population (city of Belém in the state of Pará). METHODS: Fifty individuals controlled for age and sex were assessed in each region, and the major risk factors for coronary heart disease were analyzed. RESULTS: According to the National Cholesterol Education Program (NCEP III) and using the Framingham score, both populations had the same absolute risk of events (Vigia = 5.4 ± 1 vs Belém = 5.7 ± 1), although the population of Vigia had a lower consumption of saturated fat (P<0.0001), a greater consumption of mono- and polyunsaturated fat (P<0.03), in addition to lower values for body mass index (25.4± 0.6 vs 27.6 ± 0.7 kg/m², P<0.02), of biceps skin fold (18.6 ± 1.1 vs 27.5 ± 1.3 mm, P<0.0001), of triceps skin fold (28.7 ± 1.2 vs 37.3 ± 1.7 mm, P<0.002), and of total cholesterol (205 ± 5 vs 223 ± 6 mg/dL, P< 0.03) and triglycerides (119 ± 9 vs 177 ± 18 mg/dL, P<0.005). Both populations did not differ in regard to HDL-C (46 ± 1 vs 46 ± 1 mg/dL), LDL-C (135 ± 4 vs 144 ± 5 mg/dL) and blood pressure (SBP 124 ± 3 vs 128 ± 3 mmHg; DBP 80 ± 2 vs 82 ± 2 mmHg). CONCLUSION: The riverside and urban populations of Amazonia had similar cardiovascular risks. However, the marked difference in the variables studied suggests that different strategies of prevention should be applied

Lipid profile and cardiovascular risk in two Amazonian populations.

OBJECTIVE: To compare the lipid profiles and coronary heart disease risks of 2 Brazilian Amazonian populations as follows: a riverside population (village of Vigia) and an urban population (city of Bel m in the state of Par ). METHODS: Fifty individuals controlled for age and sex were assessed in each region, and the major risk factors for coronary heart disease were analyzed. RESULTS: According to the National Cholesterol Education Program (NCEP III) and using the Framingham score, both populations had the same absolute risk of events (Vigia = 5.4 +/- 1 vs Bel m = 5.7 +/- 1), although the population of Vigia had a lower consumption of saturated fat (P<0.0001), a greater consumption of mono- and polyunsaturated fat (P<0.03), in addition to lower values for body mass index (25.4 +/- 0.6 vs 27.6 +/- 0.7 kg/m , P<0.02), of biceps skin fold (18.6 1.1 vs 27.5 +/- 1.3 mm, P<0.0001), of triceps skin fold (28.7 +/- 1.2 vs 37.3 +/- 1.7 mm, P<0.002), and of total cholesterol (205 +/- 5 vs 223 +/- 6 mg/dL, P< 0.03) and triglycerides (119 +/- 9 vs 177 +/- 18 mg/dL, P<0.005). Both populations did not differ in regard to HDL-C (46 +/- 1 vs 46 +/- 1 mg/dL), LDL-C (135 +/- 4 vs 144 +/- 5 mg/dL) and blood pressure (SBP 124 +/- 3 vs 128 +/- 3 mmHg; DBP 80 +/- 2 vs 82 +/- 2 mmHg). CONCLUSION: The riverside and urban populations of Amazonia had similar cardiovascular risks. However, the marked difference in the variables studied suggests that different strategies of prevention should be applied.

Enalaprilato na prevençäo da hipertrofia ventricular esquerda induzida pelo isoproterenol / Enalaprilat prevents the left ventricular hypertrophy induced by isoproteronol

OBJETIVO: Avaliar se o enalaprilato, droga inibidora da enzina de conversäo da angiotensina I, previne a hipertrofia ventricular esquerda (HVE) induzida pelo isoproterenol. MÉTODOS: Foram divididos em 4 grupos, 72 ratos Wistar-EPM: CON controle; ENA, tratados com enalaprilato ( 1 mg/kg via subcutânea (sc) por 8 dias); ISO, tratados com isoproterenol (0,3 mg/kg via sc/8 dias) e ENA+ISO, tratados simultaneamente com ambas as drogas. Em 10 animais de cada grupo foram determinadas a freqüência cardíaca (FC) e a pressäo arterial (PA) e verificado o peso de ventrículo esquerdo (VE). Em 8 animais de cada grupo, fragmento do VE foi corado com hematoxilia-eosina e picro-sírius e preparado para estudo morfométrico e ultra-estrutural, respectivamente, com microscópio de luz e eletrônico. RESULTADOS: Nos grupos estudados (CON, ENA, ISO e ISO+ENA) näo ocorreram variaçöes na PA. Os grupos ISO e ISO+ENA exibiram aumentos significantes na FC. O grupo ISO apresentou aumento significantivo do peso do VE(PU=0,821g e PS=0,204g), quando comparado ao grupo CON. O grupo ENA näo exibiu modificaçäo de peso do VE quando comparado ao grupo CON (PU=0,590g e PS=0,139g). No grupo ENA+ISO (PU=0,737g e PS=0,177g) constatou-se diferença de peso ao ser comparado aos grupos ISO e CON. A análise morfométrica e ultra-estrutural mostraram que o ISO induziu hipertrofia dos cardiomiócitos e aumento do tecido do tecido conjuntivo com depósito de fibras colágenas do tipo I. O enalaprilato associado com isoproterenol atenuou importantemente aquela manifestaçäo. CONCLUSÄO: O enalaprilato inibiu a açäo do isoproterenol sobre os cardiomiócitos, evitando parcialmente, na dose utilizada, a HVE e diminuindo também a quantidade de fibras colágenas.