NEW YORK – Clinical trials using biomarkers to guide therapy in systolic heart failure have shown that, while the approach is still considered investigative, it may help identify patients at risk of hospitalization, heart attack or death, according to Dr. Hans Peter Brunner-La Rocca of Maastricht (Netherlands) University.
Dr. Brunner-La Rocca presented an update on the use of intensified therapy guided by B-type natriuretic peptide (BNP) at the annual New York Cardiovascular Symposium. "The predictive value of BNP is quite high," he said. "If you see a patient for the first time who is untreated with low BNP, heart failure is rather unlikely." Dr. Brunner-La Rocca is a coinvestigator of TIME-CHF (Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure) (JAMA 2009;301:383-92).
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While BNP-guided biomarker therapy has not been tested sufficiently to merit widespread use, it can be helpful in identifying at-risk patients, Dr. Brunner-La Rocca said. It can treat underlying coronary artery disease, heart valve disease or myocarditis, or complications from mitral valve regurgitation and anemia. He listed three prognostic factors that can help guide therapy: spiro-ergometry in transplantation, left ventricular ejection fraction in patients with implantable cardioverter devices, and hemodynamics.
Dr. Brunner-La Rocca discussed seven clinical trials that treated almost 14,000 patients with N-terminal BNP (NT-BNP) and almost 800 with BNP guidance. The TIME-CHF trial of NT-BNP showed that patients under age 75 years who had intensified BNP-guided therapy had fewer hospitalizations, improved survival, and fewer symptoms of heart failure than did those who received standard treatment. However, patients over age 75 showed almost identical outcomes for the BNP and standard therapy groups after 18 months.
"An end point we looked at was hospitalization-free survival because we thought when we intensify therapy maybe we do something good for the heart, but we’re not so certain when we provoke more side effects," he said. Compared with the symptom-guided group, the NT-BNP–guided group had fewer hospitalizations – 28% vs. 38% in the standard treatment group.
Meanwhile, Dr. Brunner-La Rocca pointed out the Systolic Heart Failure Treatment Supported by BNP (STARS-BNP) trial "showed a positive effect on survival and extensive reduction in cardiac events" (N. Engl. J. Med. 2008;358:2148-59).
However, Dr. Brunner-La Rocca also noted that the variance among the studies analyzed may cause confusion about the effectiveness of BNP-guided therapy. "The other studies were not all that positive," he said. "The largest study so far actually showed a negative result – basically no effect at all – and reported a substantial amount of events."
Two more recent meta-analyses have shown improved survival with BNP guidance (Arch. Intern. Med. 2010;170:507-14 and Am. Heart J. 2009;158:422-30). "When I looked at the results, I’m not quite sure where these numbers are coming from," Dr. Brunner-La Rocca said. "I think this part of the analysis is to some extent flawed."
An ongoing analysis of all the BNP trials may provide some answers when its results are published, he said.
Still, he uses BNP-guided therapy in some of his patients. "I happen to think it is still of value, particularly if I have doubts about the patient’s diagnostics," Dr. Brunner-La Rocca said. "Many of these patients have other disease, and to really know the BNP can help differentiate if the heart or some other disease mechanism is to blame. In addition, it may help to identify patients at risk, particularly younger ones."
Dr. Brunner-La Rocca had no disclosures.