ABSTRACT
OBJETIVO: O estudo LOTHAR avaliou a eficácia, tolerabilidade e os efeitos metabólicos em médio e longo prazo (um ano) da combinação fixa de anlodipino e losartana versus anlodipino e losartana isoladamente. MÉTODOS: Estudo multicêntrico brasileiro, randomizado, duplo-cego e comparativo realizado com 198 pacientes com hipertensão arterial primária em estágios 1 e 2. RESULTADOS: A combinação fixa apresenta alta eficácia anti-hipertensiva que se mantém em longo prazo com percentual reduzido de escape do controle pressórico, inferior a dos dois regimes monoterápicos de comparação. Em longo prazo, mais de 60 por cento dos pacientes tratados com a combinação fixa permaneceram com níveis da PAD < 85 mmHg e o efeito anti-hipertensivo quando avaliado pela MAPA persistiu nas 24 horas com relação vale-pico de 76,7 por cento. A freqüência de eventos adversos foi bastante reduzida neste grupo sendo a incidência em longo prazo de edema de membros inferiores cerca de quatro vezes menor que a observada com o anlodipino isolado. A combinação fixa não alterou os metabolismos da glicose e dos lípides tanto em médio quanto em longo prazos. CONCLUSAO: Estes resultados nos permitem afirmar que a combinação de anlodipino e losartana, a primeira combinação fixa de um antagonista dos canais de cálcio e um bloqueador do receptor da angiotensina II disponível no mercado farmacêutico constitui-se em excelente opção para o tratamento da hipertensão arterial em larga gama de pacientes hipertensos.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Amlodipine/administration & dosage , Antihypertensive Agents/administration & dosage , Hypertension/drug therapy , Losartan/administration & dosage , Amlodipine/adverse effects , Amlodipine/metabolism , Antihypertensive Agents/adverse effects , Antihypertensive Agents/metabolism , Blood Pressure Monitoring, Ambulatory , Chi-Square Distribution , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Glucose/metabolism , Hypertension/metabolism , Hypertension/physiopathology , Lipid Metabolism , Losartan/adverse effects , Losartan/metabolism , Statistics, Nonparametric , Time FactorsABSTRACT
BACKGROUND & OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-alpha, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients. METHODS: Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amlodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group. RESULTS: Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-alpha and HOMAIR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin A1c and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-alpha values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-alpha and HOMA-IR. INTERPRETATION & CONCLUSION: Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-alpha levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.