The Randomized controlled multicenter Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) recruited 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 centres in Switzerland and Germany between January 2003 and June 2008.
Patients were randomly allocated to up-titration 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).
Importantly, doses of drugs with proven prognostic efficacy were uptitrated to a significantly greater extent in the N-terminal BNP–guided group vs. the symptom-guided group in both age groups.
Nevertheless, there was no significant difference in the reduction of N-terminal BNP levels between the two treatment groups in our study.
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).
Interestingly, however, at subgroup analysis, 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).
