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

Context It is uncertain whether intensified heart failure therapy guided by N- terminal brain natriuretic peptide ( BNP) is superior to symptom- guided therapy. Objective To compare 18- month outcomes of N- terminal BNP - guided vs symptomguided heart failure therapy. Design, Setting, and Patients Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure ( TIMECHF) of 499 patients aged 60 years or older with systolic heart failure ( ejection fraction <= 45%), New York Heart Association ( NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N- terminal BNP level of 2 or more times the upper limit of normal. The study had an 18- month follow- up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. Intervention Uptitration of guideline- based treatments to reduce symptoms to NYHA class of II or less ( symptom- guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less ( BNP- guided therapy). Main Outcome Measures Primary outcomes were 18- month survival free of all- cause hospitalizations and quality of life as assessed by structured validated questionnaires. Results Heart failure therapy guided by N- terminal BNP and symptom- guided therapy resulted in similar rates of survival free of all- cause hospitalizations ( 41% vs 40%, respectively; hazard ratio [ HR], 0.91 [ 95% CI, 0.72- 1.14]; P=. 39). Patients' quality- of-life metrics improved over 18 months of follow- up but these improvements were similar in both the N- terminal BNP - guided and symptom- guided strategies. Compared with the symptom- guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N- terminal BNP - guided group ( 72% vs 62%, respectively; HR, 0.68 [ 95% CI, 0.50- 0.92]; P=. 01). Heart failure therapy guided by N- terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older ( P <. 02 for interaction). Conclusion Heart failure therapy guided by N- terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom- guided treatment. Trial Registration isrctn. org Identifier: ISRCTN43596477.