Using a measure of the hormone N-terminal brain natriuretic peptide (BNP) to guide therapy for older patients with heart failure (HF) did not improve overall clinical or quality of life outcomes compared to patients receiving conventional symptom-guided therapy, according to the TIME-CHF study in the Jan. 28 issue of the Journal of the American Medical Association.
BNP is predominantly produced by the heart muscle cells and levels of BNP are increased in patients with congestive heart failure. Therapy for HF guided by N-terminal BNP has been proposed to improve outcomes compared with conventional therapy in patients with chronic HF in some studies. However, the studies were small, not conclusive, had limited follow-up and focused on younger patients, according to background information in the article.
The authors wrote that intensified N-terminal BNP–guided therapy may be particularly beneficial for older patients who are less physically active and in whom symptoms are less reliable.
Matthias Pfisterer, MD, of University Hospital Basel in Switzerland, and colleagues compared a N-terminal BNP–guided strategy to the standard symptom-guided therapy for 499 patients age 60 years or older with chronic HF, who had prior hospitalization for HF within one year and N-terminal BNP level of two or more times the upper limit of normal.
The TIME-CHF trial (Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive HF) had an 18-month follow-up. Patients were randomized to receive treatment to reduce symptoms of a certain level of heart failure (symptom-guided therapy) or treatment to reach BNP level of two times or less the upper limit of normal and reduce symptoms of a certain level of heart failure (BNP–guided therapy).
Compared with symptom-guided therapy, the investigators found that the BNP–guided strategy did not improve 18-month survival free of any hospitalization (40 percent vs. 41 percent, respectively). Overall survival rates did not differ significantly. Survival free of hospitalizations for heart failure was significantly improved with BNP–guided therapy (72 percent) compared with the symptom-guided group (62 percent).
Pfisterer and colleagues said that all measures of quality of life improved from the start of the trial to month 12 in both treatment groups and remained unchanged between month 12 and month 18. There were no significant differences in the magnitude of these improvements between the two treatment strategies.
HF therapy guided by BNP improved outcomes in patients aged 60 to 75 years, but not in those aged 75 years or older.
“The findings of the TIME-CHF study suggest that persistence in intensifying medical therapy seems to be the key for an optimal clinical outcome in patients aged 60 to 74 years, whereas it may not be beneficial to push doses to the limits in patients aged 75 years or older," the authors wrote. "Together with the main results of the TIME-CHF study, this study underscores the need for new trials specifically addressing the large population of older heart failure patients.”