BNP-guided med adjustments in chronic HF can cut death/hospitalization risk

April 17, 2007

Washington, DC - With hopes of making the medical therapy of chronic heart failure less of an art and more of a science, the natriuretic peptides are under scrutiny as possible targets for medical therapy in the outpatient setting. A randomized trial, one of several exploring the issue and among the first to make it into print, suggested that the biomarker-guided approach as a complement to traditional clinically driven management led to greater use of evidence-based medications and fewer clinical events[1].

Clinicians in the Systolic Heart Failure Treatment Supported by BNP (STARS-BNP) trial prescribed more diuretics and especially ACE inhibitors and beta blockers when they aimed dosage adjustments at the achievement of plasma brain-type natriuretic peptide (BNP) levels of <100 pg/mL, compared with guidance solely by clinical signs and symptoms. The BNP-guided strategy was also associated with a significant drop in the rate of the primary end point, HF-related death or hospitalization.

The benefits observed in the study using the BNP-guided approach "might actually be larger in routine clinical practice," according to the authors, Dr Patrick Jourdain (Hospitalier de René Dubos, Pontoise, France) and colleagues. The patients' care was led by HF specialists at dedicated heart-failure clinics, and at baseline all were on furosemide and virtually all were on beta blockers and either ACE inhibitors or angiotensin-receptor blockers (ARBs) at recommended dosage levels, they observe.

The STARS-BNP publication was published online March 30, 2007 in the Journal of the American College of Cardiology.

BNP on the frontier of HF management

"Identifying useful strategies to facilitate HF monitoring is a very high priority in the heart-failure world, as the availability of multiple effective therapeutic interventions now creates a need for 'guides' that will let us know when patients are adequately treated," observes Dr Clyde W Yancy (Baylor University Medical Center, Dallas, TX), who wasn't involved in STARS-BNP. Methods under exploration, he told heart wire , include biomarkers like the natriuretic peptides, automated daily-weight algorithms, remote HF-status monitoring systems, and implantable hemodynamic monitors. "Nothing to date has been definitively demonstrated to be truly superior to clinical judgment."

There is much evidence supporting levels of BNP as a risk stratifier in the setting of acute MI and hospitalization for acute decompensated HF, Yancy observed, "However, the unanswered question is whether or not targeting a lowered BNP level via medical, device, or surgical management will lead to better outcomes."

STARS-BNP randomized 220 patients in NYHA functional class 2-3 with an LVEF <45% to one of the two outpatient management strategies, BNP-guidance as a supplement to clinical judgment vs the traditional approach on its own. During the first three months, medical therapy was adjusted 134 times among the 110 patients in the BNP-guidance group—specifically in pursuit of the BNP target on about 80% of occasions; medications were changed 66 times among the 110 clinically managed patients (p<0.05). In both groups, about 40% of the changes were to the diuretic dosage. But ACE-inhibitor/ARB and beta-blocker use increased more in the BNP-guidance group.

Changes in per-patient use of evidence-based medical therapy during first three months (mean % of recommended dosage received)

Medical therapy by group Baseline (%) 3 mo (%) p
ACE inhibitors/ARBs      
BNP-guided therapy 94 106 <0.05
Standard management 94 98 NS
Beta blockers      
BNP-guided therapy 58 77 <0.05
Standard management 57 67 <0.05

The plasma-level target was somewhat elusive in the BNP-guidance group; mean concentrations went from 352 pg/mL at baseline to 284 pg/mL after three months (p=0.03), and the proportion reaching the target went from 16% to 33% (p=0.04).

Still, patients on BNP-guided management showed a significant decrease in the primary end point of death or unplanned hospitalization due to heart failure, fewer HF-related hospitalizations, and better event-free survival. There were no significant differences in all-cause mortality or all-cause hospitalization.

Clinical outcomes after at least six months of therapy (median, 15 months)

End point BNP-guided therapy, n=110 (%) Clinically guided therapy, n=110 (%) p
HF-related death or unplanned hospitalization* 24 52 <0.001
Event-free survival 84 73 <0.01
HF-related hospitalization 20 44 <0.0001
*Primary end point

STARS-BNP is among the first of a number of trials exploring whether natriuretic-peptide-guided outpatient management can be a both effective and practical strategy. It was associated with fewer CV events, including hospitalization, in a pioneering trial with fewer than 70 patients published in 2000[2]. Others that are ongoing or in the works have vivid acronyms like ESCAPE, TIME-CHF, RABBIT, and BATTLESCARRED[3,4]

STARS-BNP in context

Another of the trials, presented in preliminary form at the American Heart Association 2006 Scientific Sessions but as yet unpublished, is the pilot study STARBRITE[5]. As reported by Dr Monica R Shah (Washington Hospital Center, Washington, DC), the 130-patient trial found no significant difference over three months between BNP-guided and solely clinically based management in the primary end point of "nonhospital days alive."

Compared with STARS-BNP, however, STARBRITE entered an arguably sicker group of patients. They started out in NYHA class 3-4 and with an LVEF <35% and had been randomized prior to discharge following hospitalization for acute decompensation. Also different was the study's BNP target for medical therapy, which was maintenance at less than twice the BNP concentration at hospital discharge.

Similar to STARS-BNP, STARBRITE saw significantly increased ACE-inhibitor use (p=0.03) and a trend toward greater use of beta blockers (p=0.08) in the BNP-guidance group.

Yancy called STARS-BNP "provocative" but in need of verification by larger trials that account for the full range of available treatment options for heart failure. The findings, he said, "would suggest that BNP-guided therapy has some advantages over clinical assessment, but there are important caveats. These data are likely to be very center-specific and, as the authors point out, very much patient-specific. We don't know how the findings would be altered with a larger patient population, with a more diverse population, and especially with the use of evidence-based device therapy."

STARS-BNP was funded by Biosite, for which Yancy reports he is a consultant.

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