Although a number of studies have previously investigated the utility of N-terminal brain natriuretic peptide (BNP) to guide treatment for heart failure, these studies were limited by their small size and limited follow-up. The Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) aimed to overcome these limitations.
In this study, Pfisterer and colleagues randomized 499 patients to uptitration of guideline-based heart failure treatment according to symptoms (to achieve New York Hear Association [NYHA] class II or less), or instead to treatment geared to reducing the level of BNP to less than two times the upper limit of normal. All patients were aged 60 years or more, had an echocardiographic ejection fraction of 45% or less, and had NYHA class II or greater heart failure. The main outcome measure was 18-month survival free of all-cause hospitalizations and quality of life scores.
No difference was seen between the two management strategies in terms of survival free of all-cause hospitalisations (41% vs 40% respectively; hazard ratio [HR], 0.91; p=.39), and both groups showed similar improvements in quality of life over the 18-month period. In the group treated according to BNP levels, survival free of hospitalization for heart failure (a secondary endpoint) was greater (72% vs 62%; HR, 0.68; p=.01). In addition those aged 60-75 showed superior hazard ratios compared to those over 75; by 30% (p=0.05) for hospitalization-free survival, 59% (p=0.02) for overall survival, and 58% (p=0.002) for hospitalization-free survival for biomarker-guided vs symptom-guided therapy. However, these differences were not noted in patients aged over 75.
Although not reaching it’s primary endpoint, the trial raises some interesting results. A biomarker-guided strategy may be of limited value in the elderly, but may have some benefit in younger patients who would currently be considered optimally treated according to their symptoms. Therefore the trial reminds us that even in asymptomatic patients, it is important to uptitrate medications to improve outcomes.
· Pfisterer M, Buser P, Rickli H, et al. BNP-guided vs symptom-guided heart failure therapy: The Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA 2009; 301:383-392.
· Piña IL, O’Connor C. BNP-guided therapy for heart failure. JAMA 2009; 301:432-434.