Biomarkers as a guide to therapy in heart failure patients

There has been much interest in the biomarker known as N-terminal brain natriuretic peptide (BNP) as a precise guide for the diagnosis, prognosis and treatment of heart failure. Earlier studies showed that this peptide released by the heart muscle in response to stress lowers blood pressure and has diuretic properties, with levels increased in patients with heart failure. Hence the interest in this peptide as a marker for the exclusion or presence and severity of heart failure.

Now, a randomised trial reported in JAMA suggests that, while using BNP as a marker to guide therapy is not associated with any improvement in all-cause outcome over conventional symptom-guided therapy, there is indeed a benefit in hospital-free survival in heart failure patients under the age of 75.

The study (Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure [TIME-CHF]) was performed in 499 patients age 60 years or older hospitalised for heart failure within the past year and with N-terminal BNP levels at least twice the upper limit of normal. The subjects were randomised to receive treatment to reduce symptoms (symptom-guided therapy) or intensive treatment to reach a BNP level of no more than twice the upper limit of normal and reduce symptoms (BNP - guided therapy). The study population was then prospectively stratified into two age groups, under and over 75 years.

After a follow-up of 18 months, the BNP-guided strategy and symptom-guided strategies had similar outcomes with respect to all-cause hospitalisation (41% vs 40%) and survival. However, survival without hospitalisation for heart failure was significantly improved with BNP - guided therapy (72% vs. 62%). This benefit was not apparent in patients over the age of 75.

Thus, the study authors 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.'

Commenting on the study on behalf of the European Society of Cardiology, Professor Kenneth Dickstein from Stavanger University Hospital in Norway emphasises the study's difference in outcome between the under and over-75s. 'The older people in this study did not do as well as the younger and did not respond as well to therapy,' he says. 'So we still need trials properly powered to show the effect of BNP measurement as a marker in elderly patients who more closely reflect our everyday heart failure populations today. So, while we saw a benefit of intensive therapy guided by BNP levels in younger patients in this study, we didn't see it in the over-75s, who generally had more advanced disease, co-morbidity and higher BNP levels.'

The study also showed that continual monitoring of BNP levels (performed at 1, 3, 6, 12 and 18 months in the BNP group) as a guide to treatment was not associated with any improvement in outcome: 'A baseline measurement of BNP may be enough to initiate effective therapy,' says Professor Dickstein. 'Serial measurements do not appear to have added value.'