RESUMEN
Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria. In this study, 268 children were re-randomized to losartan or enalapril and followed until 100 patients completed 3 years of follow-up for proteinuria and renal function. The least squares percent mean reduction from baseline in the urinary protein/creatinine ratio was 30.01% for losartan and 40.45% for enalapril. The least squares mean change from baseline in eGFR was 3.3 ml/min per 1.73 m2 for losartan and 7.0 ml/min per 1.73 m2 for enalapril. The incidence of specific adverse events such as hyperkalemia and renal dysfunction was low and similar in both groups. Both were generally well tolerated and, overall, fewer drug-related adverse events occurred with losartan than with enalapril. Thus, in children with proteinuria, losartan and enalapril significantly reduced proteinuria without any appreciable changes in eGFR, effects that were maintained throughout the study. Both losartan and enalapril were generally well tolerated.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enalapril/uso terapéutico , Losartán/uso terapéutico , Proteinuria/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Adolescente , Factores de Edad , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Biomarcadores/sangre , Biomarcadores/orina , Niño , Preescolar , Creatinina/orina , Cistatina C/sangre , Enalapril/efectos adversos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Análisis de los Mínimos Cuadrados , Losartán/efectos adversos , Masculino , Proteinuria/sangre , Proteinuria/fisiopatología , Proteinuria/orina , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/orina , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors improves outcomes and symptoms in patients with heart failure (HF). We compared effects of losartan to captopril on mortality, morbidity, and functional status for patients in the ELITE II study. METHODS AND RESULTS: A total of 3152 patients, aged 60 years or older, with New York Heart Association (NYHA) classes II to IV HF and ejection fraction < or = 40% were assigned to receive losartan 50 mg once daily or captopril 50 mg 3 times daily. Outcome measures included all-cause and HF-related mortality, hospitalizations, and discontinuations; change in NYHA class; and quality of life (QoL). HF-related outcomes were not significantly different between therapies. Similar improvements from baseline (P < .01) in NYHA class were observed within both treatment groups. Among 1856 QoL participants, 1343 patients survived at least 1 year; the QoL for 1-year survivors improved in both treatment groups (P < .001 vs baseline) and did not differ between groups. CONCLUSIONS: In ELITE II, the effects of losartan on HF-related outcomes, NYHA class, and QoL were not superior to those of captopril. Although angiotensin-converting enzyme inhibitors remain the treatment of choice for patients with HF, the similarity of the findings in the present analysis supports a role for angiotensin-receptor antagonists in this patient population.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Losartán/uso terapéutico , Anciano , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Masculino , SobrevidaRESUMEN
BACKGROUND: The aim of this study was to determine the dose-response relationship for losartan, 2.5 to 100 mg, and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age. METHODS: This was a multicenter, randomized, double-blind, dose-response study. In Period 1, a total of 175 patients were stratified by weight (<50 kg and >/=50 kg) and randomized to one of three dose groups by stratum (low, 2.5/5.0 mg; middle, 25/50 mg; or high, 50/100 mg) for 3 weeks. The ratio of the three dose levels for both weight strata was 1:10:20. In Period 2, patients in each dose group were randomized to continue the same treatment or placebo washout for 2 additional weeks. RESULTS: In Period 1, sitting trough diastolic blood pressure (DBP) decreased in a dose-dependent manner (P < .0001). At week 3, changes in DBP from baseline in the low-, middle-, and high-dose groups were -6.0 mm Hg, -11.7 mm Hg, and -12.2 mm Hg, respectively. In Period 2, DBP increased significantly in patients who switched from middle- and high-dose losartan to placebo (mean increase 6.0 mm Hg, P = .003) relative to DBP in patients who remained on active treatment; however, these levels remained stable in those patients who switched from low-dose losartan to placebo (mean increase 1.1 mm Hg, P = .628). CONCLUSIONS: In hypertensive children 6 to 16 years of age, losartan given once daily reduced blood pressure in a dose-dependent fashion. A once-daily starting dose of losartan, 0.75 mg/kg (maximum 50 mg) effectively lowered DBP within 3 weeks. Losartan up to a dosage of 1.44 mg/kg (maximum 100 mg) once daily is generally well tolerated.