Using Heart Biomarker Levels to Guide Therapy Does Not Improve Outcomes for Heart Failure Patients


Using a measure of the hormone N-terminal brain natriuretic peptide (BNP) to guide therapy for older patients with heart failure did not improve overall clinical or quality of life outcomes compared to patients receiving conventional symptom-guided therapy, according to a study in the January 28 issue of JAMA1.


BNP is produced predominantly by the heart muscle cells, and levels of BNP are increased in patients with congestive heart failure. Therapy for heart failure guided by N-terminal BNP has been proposed to improve outcomes compared with conventional therapy in patients with chronic heart failure in some studies. However, these studies were small, not conclusive, had limited follow-up and focused on younger patients, according to background information in the article. 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. Heart failure is the most common reason for hospitalization in patients age 65 years or older.


Matthias Pfisterer, M.D., of University Hospital Basel, 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 heart failure, who had 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 (Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure [TIME-CHF]) 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 2 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 BNP–guided strategy did not improve 18-month survival free of any hospitalization (41 percent for BNP–guided group vs. 40 percent for symptom-guided group). Overall survival rates did not differ significantly. Survival free of hospitalizations for heart failure was significantly improved with BNP–guided therapy (72 percent vs. 62 percent for symptom-guided group).


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.


Heart failure therapy guided by BNP improved outcomes in patients age 60 to 75 years but not in those age 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 write. “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.”


Ileana L. Piña, M.D., of Case Western Reserve University and Louis Stokes VA Medical Center, Cleveland, and Christopher O’Connor, M.D., of Duke University, Durham, N.C., write in an accompanying editorial2 that there may be some usefulness of BNP as a biomarker of heart failure.


“… the time course of heart failure therapy is gradual, composed of uptitration of medications, reassessment of patient symptoms and signs, clinician persistence and patience, and obtaining BNP levels. There are no easy answers and no simple solutions in the search for a single biomarker for diagnosis, prognosis, and treatment of heart failure. While the BNP level may prove to be a useful tool for guiding therapy, it may be the method of reduction of BNP levels that matters most in improving outcomes for patients with heart failure.”





1. JAMA. 2009;301[4]:383-392.

2. JAMA. 2009;301[4]:432-434.