Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

OBJECTIVE: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure. METHODS: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999. RESULTS: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm5.m2, cardiac index 2.8 L/min.m2, and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements. CONCLUSION: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence. .

Inibidor da ECA e concentrações do peptídeo natriurético do tipo B, em idosos com insuficiência cardíaca / ACE inhibitors and plasma B-type natriuretic peptide levels in elderly patients with heart failure / Inhibidor de la enzima conversora de la angiotensina y concentraciones del péptido natriurético de tipo B, en personas adultas mayores con insuficiencia cardiaca

Fundamento: Ensaios clínicos demonstraram os benefícios dos inibidores da ECA (IECA) na atividade neuro-hormonal e na capacidade funcional de pacientes com insuficiência cardíaca (IC), com a magnitude desses efeitos sendo proporcional à dose desses agentes. Entretanto, a sistemática exclusão dos idosos, observada na maioria desses estudos, tem questionado a validação e incorporação de tais resultados na população geriátrica. Objetivo: Avaliar os efeitos de diferentes doses de quinapril, um IECA com meia vida biológica >24 horas, nas concentrações plasmáticas do PNB, nas distâncias percorridas no teste da caminhada de 6 minutos (TC-6 min) e na incidência de reações adversas, em idosos com IC sistólica. Métodos: Foram avaliados 30 pacientes (76,1 ± 5,3 anos; 15 mulheres), IC II-III (NYHA), FE ventricular esquerda < 40% (33,5 ± 4,5%), em uso de diuréticos (30), digoxina (24) e nitratos (13). As avaliações foram realizadas no momento da inclusão (basal) e a cada dois meses, com a adição de 10, 20, 30 e 40 mg de quinapril. Resultados: Completados oito meses, as concentrações do PNB foram 67,4% menores e as distâncias percorridas no TC-6 min 64,9% maiores em relação à condição basal. Hipotensão arterial com sintomas de baixo débito cerebral e/ou disfunção renal não foram observadas, possibilitando o emprego da dose máxima de quinapril em todos os pacientes. Conclusão: Os resultados demonstraram os benefícios dos IECA no perfil neuro-hormonal e na capacidade funcional de idosos com IC sistólica, bem como a relação positiva entre a dose e o efeito desses fármacos.

Background: Clinical trials have demonstrated the benefits of ACE inhibitors (ACEI) in the neurohormonal activity and in the functional capacity of patients with heart failure (HF), and also that these effects are dose dependent. However, since elderly individuals have been systematically excluded from the majority of these studies, the validation and incorporation of these results in the geriatric population has been questioned. Objective: To evaluate the effects of different doses of quinapril, an ACEI with a > 24-hour biological half-life, on plasma BNP levels, on the distance walked in the 6-minute walk test (6MWT) and on the incidence of adverse reactions in elderly individuals with systolic HF. Methods: A total of 30 patients (76.1 ± 5.3 years; 15 women), in NYHA functional class II-III HF, with left ventricular EF < 40% (33.5 ± 4.5%), on diuretics (30), digoxin (24) and nitrates (13) were included. The patients were assessed at baseline and every two months, with escalating doses of quinapril of 10, 20, 30 and 40 mg.Results: After eight months, BNP levels were 67.4% lower and the distance walked in the 6MWT was 64.9% longer in relation to baseline. Arterial hypotension with symptoms of low cerebral blood flow and/or renal dysfunction was not observed, so that the maximum quinapril dose could be used in all patients. Conclusion: The results demonstrated the benefits of ACEI on the neurohormonal profile and functional capacity of elderly individuals with systolic HF, as well as the positive relationship between dose and effect of these drugs.

Fundamento: Ensayos clínicos revelaron los beneficios de los inhibidores de la enzima conversora de la angiotensina (IECA) en la actividad neurohormonal y en la capacidad funcional de pacientes con insuficiencia cardiaca (IC). La magnitud de esos efectos fue proporcional a la dosificación de esos agentes. Sin embargo, la sistemática exclusión de las personas adultas mayores, observada en la mayoría de esos estudios, ha conllevado al cuestionamiento de la validación e incorporación de dichos resultados en la población geriátrica. Objetivo: Evaluar los efectos de diferentes dosis de quinapril, un IECA con vida media biológica >24 horas, en las concentraciones plasmáticas del péptido natriurético de tipo B (PNB), en las distancias recorridas en el test de marcha de 6 minutos (TM6m) y en la incidencia de reacciones adversas, en personas adultas mayores con IC sistólica. Métodos: Se evaluaron a 30 pacientes (76,1 ± 5,3 años; 15 mujeres), IC II-III (NYHA), fracción de eyección (FE) ventricular izquierda < 40% (33,5 ± 4,5%), en uso de diuréticos (30), digoxina (24) y nitratos (13). Las evaluaciones se realizaron a la inclusión (basal) y a cada dos meses, con la adición de 10, 20, 30 y 40 mg de quinapril. Resultados: Completados ocho meses, las concentraciones del PNB fueron de un 67,4% menor y las distancias recorridas en el TM6m de un 64,9% mayor con relación a la condición basal. No se observaron hipotensión arterial con síntomas de bajo débito cerebral y/o disfunción renal, posibilitando así el empleo de la dosificación máxima de quinapril en todos los pacientes. Conclusión: Los resultados revelaron los beneficios de los IECA en el perfil neurohormonal y en la capacidad funcional de personas adultas mayores con IC sistólica, así como la relación positiva entre la dosificación y el efecto de esos fármacos.