Should target natriuretic peptide levels be used for outpatient management of chronic heart failure?
Three negative trials
Conversely, three trials did not find significant reductions in rates of death or hospitalization-free survival between groups:
The STARBRITE trial (Strategies for Tailoring Advanced Heart Failure Regimens in the Outpatient Setting: Brain Natriuretic Peptide Versus the Clinical Congestion Score) (N = 130)15
The BATTLESCARRED trial (NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death) (N = 364)16
The PRIMA trial (Can Pro-brain-natriuretic Peptide Guided Therapy of Chronic Heart Failure Improve Heart Failure Morbidity and Mortality?) (N = 345).17
One trial with mixed results
The TIME-CHF (Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure),18 the largest of these trials to date (N = 499), did not show a survival benefit, but it did show a lower rate of hospitalization due to heart failure in the group receiving treatment guided by N-terminal BNP levels than in controls. Also, this study found that in the subset of patients younger than 75 years, therapy guided by N-terminal BNP levels reduced the risk of death and hospitalization from heart failure.
Why the different results in these studies?
Several reasons can be invoked to explain the heterogeneity of results in the studies mentioned above. Most importantly, the small sample sizes in these trials may have prevented differences from reaching statistical significance. Also, the inclusion criteria and methods varied considerably, with different natriuretic peptide targets, doses of medications, and treatment strategies.
WHAT IS THE CONCLUSION?
Although there are data to suggest that serial natriuretic peptide guidance can reduce the rates of hospitalization and death from heart failure in patients under age 75, there is not enough evidence to recommend routine measurements for the outpatient management of heart failure.
A 2009 focused update to the joint American College of Cardiology and American Heart Association 2005 guidelines19 concluded that using natriuretic peptide levels to guide heart failure therapy is not well established (class 2b, level of evidence C).
Measurement of natriuretic peptides can be useful in evaluating and risk-stratifying patients presenting in the urgent care setting in whom the clinical diagnosis of heart failure is uncertain. These measurements are to be viewed as part of the total evaluation but are not to be used in isolation to confirm or exclude the presence of heart failure or to monitor the patient for decompensation.
Natriuretic peptide measurement is not a substitute for the information derived from a good history (dyspnea, orthopnea, paroxysmal nocturnal dyspnea) and physical examination (eg, weight, jugular venous distention, crackles, a third heart sound, edema).
The consensus opinion remains that the favorable outcomes with natriuretic peptide guidance in clinical trials were due to better adherence and continuous up-titration of medications to maximally tolerated target doses of angiotensin-converting enzyme inhibitors and beta-blockers, in addition to closer follow-up of patients in those groups.20 This can be done without serial natriuretic peptide measurements.
