ACC 2009: NT-ProBNP Guidance Fails to Significantly Improve Morbidity and Mortality of Chronic Heart Failure

Fran Lowry

March 29, 2009

March 29, 2009 (Orlando, Florida) Using individualized levels of the biomarker NT-proBNP to guide the treatment of patients with chronic heart failure did not improve their morbidity or mortality over standard clinical management, according to results of the Can Pro-Brain-Natriuretic Peptide Guided Therapy of Chronic Heart Failure Improve Heart Failure Morbidity and Mortality? (PRIMA) study presented here at the American College of Cardiology 2009 Scientific Sessions.

However, a substudy of patients who stayed on target with their NT-proBNP levels for 75% or more of their follow-up visits did have significantly improved mortality, and this result, although it merits further scrutiny, means that the value of the marker may lie in its prognostic utility, said study coordinator Dr Luc Eurlings (Maastricht University Medical Center, the Netherlands).

One Size Does Not Fit All

The premise for PRIMA was that individual levels of NT-proBNP would be more useful in guiding treatment of chronic heart failure than set target levels. A previous study, the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-CHF), reported by heartwire , used fixed target levels (400 pg/mL) of NT-proBNP to guide congestive-heart-failure management but failed to show a reduction in mortality.

PRIMA enrolled 345 congestive-heart-failure patients who were hospitalized with elevated NT-proBNP levels (>1700 pg/mL). After their NT-proBNP levels dropped by more than 10% (to 850 pg/mL or less), patients were randomized to receive NT-proBNP-guided treatment (n=174) or clinically guided treatment (n=171). Serum levels of NT-proBNP were measured at discharge and again at the first follow-up period (two weeks postdischarge). The lesser of the two values was deemed the target value. If the NT-proBNP levels in patients in the guided-treatment group showed any increase at any subsequent follow-up, more intensive heart-failure therapy was immediately instituted.

At a median follow-up of 702 days (range 488 to 730) there was a small but nonsignificant increase in the trial’s primary end point--number of days alive outside the hospital--among patients in the NT-proBNP-guided group.

Number of Days Alive Outside the Hospital: NT-ProBNP-Guided Patients vs Clinically Guided Patients

PRIMA end points NT-proBNP-guided group Clinically guided group p
Number of days alive outside the hospital 685 664 0.49
Total mortality 46/174 (26.5%) 57/171 (33.3%) 0.196

Significantly Better Outcomes in Patients Who Stayed "On Target"

Although tailoring therapy to individual target levels did not appear to confer a survival advantage overall, a subanalysis of 101 NT-proBNP patients who stayed at their target levels for 75% or more of their follow-up visits had significantly reduced mortality, compared with clinically guided patients. But if these patients went above their set target, their mortality rates were significantly increased (rising to 50%), said Eurlings.

Number of Days Alive Outside the Hospital: On-Target NT-ProBNP-Guided Patients vs Clinically Guided Patients

PRIMA end points NT-proBNP-guided on-target group Clinically guided group p
Number of days alive outside the hospital 721 664 <0.001
Mortality 11/109 (10.9%) 57/171 (33.3%) <0.001

Will NT-Probnp Find Its Niche as a Prognostic Marker?

In an interview with heartwire , Dr Douglas Weaver (Henry Ford Hospital, Detroit, MI) noted that the "observation that [NT-proBNP] is a good prognostic marker is great, but what are we going to do with that knowledge? We don’t have a particular intervention that is going to change the outcome of those individuals."

As far as using NT-proBNP for routine monitoring, "we don’t have the evidence right now to do that. Is the issue dead? Maybe not. Other studies could be done."

But Eurlings thinks that NT-proBNP may have a future as a prognostic marker, even though its results as a guide to heart-failure therapy were less than stellar.

"I understand that Dr Weaver was very skeptical and I have sympathy for his point of view," Eurlings told heartwire . "But I do think NT-proBNP may have an important role as a prognostic indicator. We are going to be studying this further to see whether there is a subgroup of patients who may benefit from NT-proBNP-guided therapy. The patients who kept on target in this study did much better than those who did not, so there may be a place for the marker yet."

He added that clinicians owe it to their heart-failure patients to do this research. "If we could better stratify our heart-failure patients’ risk, this would most likely improve their treatment. While NT-proBNP does not help in the overall population, we have to see if there are certain subgroups that might benefit. If not, then it is a pity. But patients deserve better treatment, so we have to look at this very intensively."