Brain natriuretic peptide‐guided treatment does not improve morbidity and mortality in extensively treated patients with chronic heart failure: responders to treatment have a significantly better outcome

Abstract

Aim To determine whether brain natriuretic peptide (BNP)‐guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment. Methods and results UPSTEP was an investigator‐initiated, randomized, parallel group, multicentre study with a PROBE design. Symptomatic patients with worsening HF, New York Heart Association class II–IV, ejection fraction <40% and elevated BNP levels, were included. All patients (n= 279) were treated according to recommended guidelines and randomized to BNP‐guided (BNP) or to conventional (CTR) HF treatment. The goal was to reduce BNP levels to <150 ng/L in younger patients and <300 ng/L in elderly patients, respectively. The primary outcome was a composite of death due to any cause, need for hospitalization and worsening HF. The study groups were well matched, including for BNP concentration at entry (mean: 808 vs. 899 ng/L; P= 0.34). There were no significant differences between the groups regarding either the primary outcome (P = 0.18) or any of the secondary endpoints. There were no differences for the pre‐specified analyses; days out of hospital, and younger vs. elderly. A subgroup analysis comparing treatment responders (>30% decrease in baseline BNP value) vs. non‐responders found improved survival among responders (P< 0.0001 for the primary outcome), and all of the secondary endpoints were also improved. Conclusions Morbidity and mortality were not improved by HF treatment guided by BNP levels. However, BNP responders had a significantly better clinical outcome than non‐responders. Future research is needed to elucidate the responsible pathophysiological mechanisms in this sub‐population.

Characterization and Prediction of Natriuretic Peptide “Nonresponse” During Heart Failure Management: Results From the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT‐proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) Study

“…Consistent with above differences in remodeling indices as a function of NT-proBNP response, there was no significant improvement in diastolic filling indices among nonresponders (E/E′ from 13 [9][10][11][12][13][14][15][16][17] to 12 [10][11][12][13][14][15][16][17], P=.32) while right ventricular systolic pressure (RVSP) was only marginally lowered (from 46AE12 mmHg to 42AE11 mmHg, P=.05). In contrast, there was a significant improvement in responders, with E/E′ decreasing from 10[7-13] to 9 [6][7][8][9][10][11][12] (P=.040) and right ventricular systolic pressure decreasing from 41AE10 mm Hg to 34AE8 mm Hg, (P<.001). NT-proBNP Nonresponse and Clinical Outcomes As expected, patients who began and ended the study with an NT-proBNP 1000 pg/mL had the fewest cardiovascular events (.50AE1.23 event per patient) while those who had an NT-proBNP level >1000 pg/ mL throughout the study had the highest event rates (1.57AE1.9 events per patient, P=.003; Figure S1).…”

“…5,6 Elevated NT-proBNP has been validated for its ability to predict adverse outcomes in chronic HF, [7][8][9] and the role of serial natriuretic peptide measurement 9,10 and the novel concept of biomarker response to HF therapy have been introduced. 11,12 While the concept of biomarker-guided HF management has been examined in several trials with various designs, [13][14][15][16][17][18] data are limited on how exactly HF biomarker response should be defined and what biomarker response may mean relative to biomechanical and clinical outcomes. A better characterization of natriuretic peptide response to HF therapy, along with the ability to better understand those patients likely to be a "nonresponder" would be essential knowledge in further studying guided therapy of HF.…”

Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure

“…Positive studies derive almost exclusively from those centers which have treated the overwhelming majority of patients and have published the majority of papers on the argument; most of these authors are members of Working Groups on HF (Table 1). While 6 studies [31,33,41,42,55,56] reported encouraging trends with the NPs-guided therapy in comparison to conventional care, such as reduced events in younger patients or in patients with reduced LV ejection fraction (in these studies a very low NP level was targeted, both in the intervention arm with NP-guided and in arm without NP-guided therapy), other studies [45,[57][58][59] presented neutral results. Results derive from different approaches.…”

Natriureticus peptidek mérése szívelégtelen betegekben: a helyes laboratóriumi és klinikai gyakorlat

“…Az elmúlt évtizedben számos, nagyon heterogén vizsgálat értékelte a natriureticus peptidek szerepét a króni-kus szívelégtelenség kezelésének irányításában [39,40,41,42,43,44,45,46,47,48]. Bár a legtöbb vizsgálat-ban az értékelt biomarker alkalmas volt a betegek és a betegség súlyosságának követésére, a vizsgálatok egy részében ez nem járt együtt a morbiditás és a mortalitás csökkenésével.…”