BACKGROUND: The prevalence of chronic heart failure (CHF) rises with increasing age, from < 1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general.
AIMS: The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction.
SUBJECTS: One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography.
METHODS: Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub-studies of this trial include a 6-min walking test and more detailed evaluation of ventricular function (as assessed by echocardiography). Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year. This trial is due to report in the year 2001.
OBJETIVOS: Muchos pacientes que reciben un diagnóstico de la insuficiencia cardiaca no tienen ni una baja del ventrículo izquierdo (VI) la fracción de eyección ni la enfermedad de la válvula. Pocos importantes ensayos controlados aleatorios han llevado a cabo en esta población, ninguno se ha centrado en pacientes con evidencia de disfunción diastólica y ninguno ha demostrado un claro beneficio en los síntomas, la morbilidad o la mortalidad. MÉTODOS Y RESULTADOS: Este fue un estudio aleatorizado doble ciego, comparativo con placebo con perindopril, 4 mg / día en pacientes con edad> o = 70 años con diagnóstico de insuficiencia cardíaca, tratados con diuréticos y un ecocardiograma que sugieran una disfunción diastólica del VI y la exclusión de importantes disfunción sistólica o la enfermedad de la válvula. El objetivo primario fue la combinación de mortalidad por cualquier causa y la hospitalización no planificada insuficiencia cardíaca relacionada con un seguimiento mínimo de 1 año. Un total de 850 pacientes fueron asignados al azar. Su edad media fue de 76 (SD 5) años y el 55% eran mujeres. La mediana de seguimiento fue de 2,1 (IQR 1,5-2,8) años. Las tasas de matrícula y el evento fueron inferiores a lo previsto, lo que reduce el poder del estudio para mostrar una diferencia en el objetivo primario al 35%. Muchos pacientes se retiró de perindopril (28%) y placebo (26%) después de 1 año y comenzó a tomar abierto inhibidores de la ECA. En total, 107 pacientes asignados a placebo y 100 asignado a perindopril alcanzado el objetivo primario (HR 0,919: IC 95% 0,700-1,208, p = 0,545). Por un año, las reducciones en el resultado primario (HR 0,692: IC 95% 0,474-1,010, p = 0,055) y la hospitalización por insuficiencia cardiaca (HR 0,628: IC 95% 0,408-0,966, p = 0,033) fueron observados y la clase funcional ( P <0,030) y 6-min a pie de corredor (P = 0,011) ha mejorado en los asignados a perindopril. CONCLUSIÓN: Permanece la incertidumbre sobre los efectos del perindopril en la morbilidad a largo plazo y la mortalidad en este contexto clínico ya que este estudio tenía el poder suficiente para su objetivo primario. Sin embargo, la mejoría de los síntomas y la capacidad de ejercicio y un menor número de hospitalizaciones por insuficiencia cardiaca en el primer año se observaron en perindopril, durante el cual la mayoría de los pacientes estaban en tratamiento asignado, lo que sugiere que puede ser de beneficio en esta población de pacientes.
AIM: The aim of this study was to explore the relationships between plasma concentrations of N-terminal pro brain natriuretic peptide (NT-proBNP) and characteristics and prognosis of patients with heart failure and preserved (HFPEF) left ventricular ejection fraction (LVEF). No substantial trial has shown that treatment alters prognosis in patients with HFPEF due, in part, to much lower than anticipated event rates. The lack of a simple, objective test to identify patients with HFPEF at increased risk of cardiovascular events would be valuable.
METHODS AND RESULTS: The Perindopril in Elderly People with Chronic Heart Failure Trial (PEP-CHF) was a randomized, controlled trial comparing perindopril and placebo in patients with symptoms and signs of heart failure who had an LVEF >40% and evidence of LV diastolic dysfunction. The primary endpoint was all-cause mortality or heart failure-related hospitalization. NT-proBNP was measured in 375 patients. Quartile thresholds were 176, 409, and 1035 pg/mL. Patients in the highest quartile of NT-proBNP were older, had lower body mass, more often had atrial fibrillation, had greater atrial and ventricular dimensions and a lower LVEF, and were more likely to receive loop diuretic therapy. Compared with the first quartile of NT-proBNP, the hazard ratios for the primary endpoint in the second {1.38 [95% confidence interval (CI) 0.64-2.99]}, third [2.84 (95% CI 1.42-5.72)], and fourth [4.47 (95% CI 2.30-8.72)] quartiles were increased. In a multivariable model, NT-proBNP, but not echocardiographic measures, was associated with outcome.
CONCLUSIONS: NT-proBNP is a powerful prognostic marker in patients with HFPEF.
The prevalence of chronic heart failure (CHF) rises with increasing age, from < 1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general.
AIMS:
The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction.
SUBJECTS:
One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography.
METHODS:
Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub-studies of this trial include a 6-min walking test and more detailed evaluation of ventricular function (as assessed by echocardiography). Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year. This trial is due to report in the year 2001.
