Novel Biomarker-Guided Strategy Hastens Optimal Dosing in Highest-Risk HF Patients

February 10, 2010

February 10, 2010 (Vienna, Austria) — A novel method for using natriuretic-peptide testing to optimize postdischarge therapy after acute heart-failure decompensation can cut the number of later days spent in the hospital and improve other clinical outcomes, according to researchers [1].

Their randomized study suggests that the biomarker assays can help both by singling out higher-risk patients for intensified care and then by providing targets for adjustments to their medical therapy--potentially speeding up the uptitration of beta blockers compared with contemporary nurse-led outpatient therapy.

Although other trials have explored natriuretic-peptide–guided outpatient therapy for heart failure, with mixed results (as covered by heartwire ), the biomarkers were used primarily for guidance of med dosing, not necessarily for individualizing the overall management strategy.

"Our concept was different," Dr Rudolf Berger (Medical University of Vienna, Austria), lead author of the 12-center study published in the February 16, 2010 Journal of the American College of Cardiology, told heartwire . The group's strategy uses predischarge N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to identify patients at highest risk of subsequent decompensation (NT-proBNP >2200 pg/mL) and so most likely to benefit from intensified management led by a heart-failure physician.

qNatriuretic-peptide–guided management in combination with a heart-failure clinic might increase the cost-effectiveness of heart-failure clinics per se.

That kind of frequent attention from a specialist at a heart-failure clinic can facilitate beta-blocker uptitration and lead to rapid dose optimization for diuretics and other drugs in response to rising or falling NT-proBNP levels, according to Berger.

"Doing it this way, we can uptitrate the beta blocker as quickly as possible," when otherwise--because of the short-term dampening effect beta blockers have on ventricular function--it would have to be done slowly and cautiously.

The group's method, Berger noted, contrasts with the current state of the art in many countries: management of all discharged patients by multidisciplinary teams led by heart-failure nurses, often in the home, with more limited physician involvement.

The key difference, he said, is that in most countries, even experienced heart-failure nurses do not generally take the lead in more advanced aspects of medication management, such as decisions regarding beta-blocker uptitration. They manage the delivery of medical therapy, instruct patients on the proper use of diuretics, and teach how to measure weight daily, Berger observed, but typically wouldn't adjust prescriptions in response to biomarker test results.

"It depends on the country and what heart-failure nurses are allowed to do," Berger said. But NT-proBNP–guided heart-failure therapy is most likely to be helpful when it is handled directly by heart-failure physicians and, as the current study suggests, when it is applied to patients most at risk of decompensation.

In the current study, 278 patients hospitalized with acute decompensated heart failure were randomized predischarge to one of three outpatient-care groups:

  • "Usual care," handled by the patient's primary-care physician, generally without access to heart-failure physicians or nurses.

  • HF-nurse–led "multidisciplinary care" that included multiple home visits, two prescheduled clinic visits, and on-demand physician consultations.

  • Natriuretic-peptide–guided care, consisting of multidisciplinary care, plus--only for the subgroup of patients with NT-proBNP >2200 pg/mL at discharge--visits to an HF physician at least every two weeks for optimization of medical therapy based on NT-proBNP readings and standard clinical and laboratory parameters; patients with discharge NT-proBNP levels below the 2200 pg/mL threshold, as well as those starting out with higher levels but who achieved lower levels with intensified care, went on to receive nurse-led multidisciplinary care only.

"This approach ensured rapid uptitration of therapy guided by NT-proBNP in patients at highest risk for cardiac decompensation," according to Berger et al.

Consequently, they write, "such treatment, when compared with nurse-led multidisciplinary management alone, was associated with a higher proportion of antineurohormonal triple therapy, more frequent adjustments of diuretics, a more pronounced decrease in NT-proBNP levels, and an improved outcome." Both the physician-led and nurse-led strategies produced better results than management solely by a primary-care physician.

Natriuretic-Peptide–Guided Heart-Failure Therapy, Outcomes 12 Months After Randomization

End point Usual care, n=90 Multidisciplinary care, n=96 NT-proBNP-guided care, n=92
HF-hospitalization days (d) 1588 1254a 488b,c
HF hospitalization (%) 61 40d 28
Death (%) 39 22a 22a
Death or HF hospitalization (%) 65 50a 37b,c
a. p<0.05 vs usual care

b. p<0.05 vs multidisciplinary care

c. p<0.001 vs usual care

d. p<0.01 vs usual care

Berger said that natriuretic-peptide–guided management "in combination with a heart-failure clinic might increase the cost-effectiveness of heart-failure clinics per se, because the biomarker can be used to identify the highest-risk patients with the greatest need for specialized care." At the same time, he added, it can identify the lower-risk patients who are less of a challenge to treat and don't require intensive management.

The study was supported by AstraZeneca, Novartis, Roche Diagnostics, Roche Medical, Merck, Medtronic, and Guidant.