Natriuretic Peptide-guided Therapy Research Articles

Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.

Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor-neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.

Abstract 15707: Age Does Not Modify the Impact of Natriuretic Peptide-Guided Therapy on Clinical Outcomes or Serial Natriuretic Peptide Levels

Introduction: Older age is independently associated with greater NT-proBNP levels. As such, the aim of this study was to establish the influence of age on serial NT-proBNP levels over time and the impact of age on response to natriuretic peptide-guided therapy (NPGT) versus usual care for heart failure with reduced ejection fraction (HFrEF). Hypothesis: Age will modify the effect of NPGT on serial NT-proBNP in patients with HFrEF. Methods: Using data from GUIDE-IT, the impact of age on the association of NPGT with serial NT-proBNP and long-term outcomes was assessed. Time-to-event analyses and generalized linear mixed modeling were used to evaluate the effect of age, by quartile, on long-term outcomes and serial NT-proBNP by randomized treatment (NPGT vs. usual care), respectively. Results: In this cohort (N=893), the median age was 63 [range 21-90, IQR 53-71] years and was 32% female and 36% black race. Age was modestly correlated with NT-proBNP (Spearman rho 0.34, p<0.001). At baseline, older age was associated with lower doses of ACEI/ARB (p-trend 0.019) and aldosterone antagonist use (p-trend<0.001), but not beta-blocker use (p=0.06). Older age was associated with a greater risk of all-cause death (log-rank, p<0.001) but not associated with a greater risk of combined CV death or HF hospitalization (log-rank, P=0.56). Although older age was associated with greater NT-proBNP levels over time (Q4 vs. Q1 beta 2.1 x pg/mL/days, p<0.001), it did not modify the association of NPGT on serial NT-proBNP ( Figure, Q4, Q3, and Q2 vs. Q1 by treatment arm, p-interaction>0.09 for all). Age also did not modify the impact of NPGT on either mortality or the composite, CV death or HF hospitalization (P-interaction>0.05 for both). Conclusions: Older age was associated with greater NT-proBNP levels. However, age did not modify the association of NPGT on clinical outcomes or serial NT-proBNP. These data do not support the hypothesis that age modifies the NT-proBNP response to HFrEF treatments.

Abstract 11889: Effectiveness of sST2-Guided Therapy in Patients With Heart Failure With Reduced Ejection Fraction

Introduction: Natriuretic peptide-guided therapy has not proven to be more sufficiently effective than usual care (UC) in patients with heart failure (HF). Soluble ST2 (sST2) has a number of advantages over natriuretic peptides. Hypothesis: sST2-guided therapy (sST2-GT) will be more effective than UC in patients with HFrEF. Methods: The prospective study included 76 patients (pts) with HFrEF, who were hospitalized due to acute decompensated HF. Pts with sST2 levels ≥ 37.8 ng/ml at the time of discharge constituted the high-risk cohort and were randomized into 2 groups: 19 pts in the sST2-GT and 18 patients in the UC. 39 pts with sST2 < 37.8 ng/ml and NT-proBNP < 1700 pg/ml were included in the low-risk cohort. The duration of the active treatment period was 6 months with monthly visits for therapy correction, the total follow-up period was up to 1 year. Therapy was carried out in accordance with clinical recommendations. In the sST2-GT group, therapy was also adjusted taking into account the concentration of sST2. The goal in this group was to reduce sST2 concentration by more than 30% or to less than 30 ng/ml. Measurement of sST2 (ASPECT-PLUS) concentration, echocardiography and registration combined endpoints (CEP) (HF decompensation (HFD) or cardiovascular mortality) were identified in all groups after 6 and 12 months. Results: Pts therapy in both high-risk groups was comparable, but pts in the sST2-GT group had a greater number of study clinic visits (7.1±2.3 vs 5.6±1.6 (p=0.024) compared with UC group. Pts sST2 concentration decreased in both high-risk groups, with the study goal achieved in 68,4% of pts in sST-GT group. Fewer CEP were registered In sST2-GT group pts compared to the UC group (for 6 months - 5 (0.26 / pt) vs 15 (0.83 / pt), p = 0.029 and 9 (0.47/pt) vs 22 (1.22/pt), p=0.035 over the entire follow-up) and it was practically similar low-risk cohort (0.46/patient). Fewer HFD were registered in the sST2-GT group compared to the UC group (for 6 months 4 (0.21 /pt) vs 13 (0.72 /pt), p < 0.001 and 8 (0.42/pt) vs 19 (1.06/pt), p<0.001 over entire follow-up), which was similar the low-risk group (0,31/pt). LV EF increased only in the sST2-GT group (from 29.2±6.2 up to 36.1±8.8, p=0.003 for 6 months). Conclusions: sST2-GT in high-risk pts with HFrEF is more effective than UC.

Heart failure treatment and the art of medical decision making.

Heart failure treatment and the art of medical decision making.

Natriuretic peptide-guided therapy in high-risk heart failure patients, to be or not to be?

The natriuretic peptides, B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP), are biomarkers of neurohormonal activation related to heart failure (HF) severity and associated with adverse outcomes and poor prognosis in HF patients with rising levels (1-3).

Comments on GUIDE-IT, a randomized study of natriuretic peptide-guided therapy in high-risk patients with heart failure and reduced ejection fraction

The topic of guiding therapy in heart failure patients with natriuretic peptide levels is not new: eleven trials have been performed and several meta-analyses have been published including one with individual patient data (1). The GUIDE-IT trial should have been the trial that confirmed the meta-analyses that guiding therapy with natriuretic peptides in patients with heart failure would reduce the primary endpoint of heart failure readmissions and cardiovascular mortality by 20% (2,3).

Effect of Natriuretic Peptide-Guided Therapy on Outcomes in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Effect of Natriuretic Peptide-Guided Therapy on Outcomes in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Natriuretic peptide-guided management in heart failure.

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Natriuretic Peptides and the Management of Heart Failure.

Natriuretic peptide has been validated as a useful biomarker in the diagnosis of heart failure, although its role in guiding medical management of heart failure is not well established. We endeavored to determine if natriuretic peptide-guided therapy is associated with improved outcomes for heart failure patients. A total of 11 trials (2628 patients) comparing natriuretic peptide-guided therapy with standard therapy for heart failure patients were identified; follow-up times ranged from 3 months to 3 years. Our data indicate that natriuretic peptide levels and all-cause mortality rates do not appear to benefit from natriuretic peptide-guided therapy when compared with standard therapy. However, a decreased rate of cardiovascular events does appear to be associated with natriuretic peptide-guided therapy.

B-type natriuretic peptide-guided therapy and length of hospital stay post left ventricular assist device implantation.

B-type natriuretic peptide (BNP)-guided therapy during the early postoperative period following left ventricular assist device (LVAD) implantation has not been well described in the literature. We conducted a retrospective cohort study consisting of consecutive patients who underwent LVAD implantation at our institution during May 2009 to March 2013. The study was limited to patients receiving HeartMate II (Thoratec) or HVAD (HeartWare) LVADs. Patients with acute myocardial infarction were excluded. We compared between patients with multiple postoperative BNP tests (BNP-guided therapy) and earlier period patients who typically had only a baseline BNP measurement (non-BNP-guided therapy). A total of 85 patients underwent LVAD implantation during the study period. Eight patients were excluded (five acute myocardial infarction, three without BNP measurements). The only differences in the baseline characteristics of BNP versus non-BNP-guided therapy included age and female gender. The postoperative length of hospital stay (LOS) in the BNP-guided therapy group was 5 days shorter when compared with the non-BNP-guided therapy group. In multivariate analysis, BNP-guided therapy remained a significant predictor of reduced LOS. The use of repeated BNP measurements during the early postoperative period was associated with a significantly lower LOS post LVAD implantation.

Utility of Biomarkers in Contemporary Management of Chronic Heart Failure

The current interest in guided-based therapy of acutely decompensated and chronic heart failure (CHF) is steadily increased. The measurements of circulating levels of brain natriuretic peptide (BNP) and N-terminal pro-hormone of BNP (NT-pro-BNP) to be risk stratified of the patients with symptomatic CHF is not widely approached in routine clinical practice. Likewise several conceptual, methodological, and as a result practical limitations of the natriuretic peptideguided therapy are not able to fulfilled change the contemporary strategic approach based on symptoms and echo-guided treatment of CHF. Clinically significant biological variability of natriuretic peptide level, high cost and slow time-course, as well as the lack of conclusive scientific evidence within long-term period of intensive scientific investigations may not support idea about needing new biological markers or constructing novel combinations for multiple biomarker predictive score and biomarker guided-based therapy. The review is dedicated to consideration of potency and clinical advantages of novel strategic approach in the field of CHF treatment based on serial measurements of biomarkers and creating optimal its combinations.

Does B-type natriuretic peptide-guided therapy improve outcomes in patients with chronic heart failure? A systematic review and meta-analysis of randomized controlled trials.

The role of B-type natriuretic peptide (BNP) in the management of patients with chronic heart failure (CHF) was uncertain. The aim of this meta-analysis was to comprehensively evaluate the effect of BNP-guided therapy in CHF. Relevant randomized controlled trials were identified by searching of Pubmed, Embase and the Cochrane Library databases. Fixed or randomized effect models were applied to combine the data according to the heterogeneity of the included studies. Fourteen studies with 3,004 CHF patients were included. Results of our meta-analyses suggested that compared with clinical group, BNP-guided treatment significantly decreased the risk of heart failure-related hospitalization (RR 0.79, 95 % CI 0.63-0.98, p = 0.03), although did not significantly affect the risk of all-cause mortality (RR 0.94, 95 % CI 0.81-1.08, p = 0.39) or all-cause hospitalization (RR 0.97, 95 % CI 0.89-1.07, p = 0.56). Furthermore, between-group BNP changes seemed to be a significant modifier to the effects of BNP-guided therapy on clinical outcomes, and BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. In addition, BNP-guided therapy was not associated with increased risk for serious adverse events. BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. BNP-guided therapy seemed to be safe and promising for CHF patients, and future studies with well-designed BNP-guided medication up-titration strategies are needed to confirm these results.

Polypharmacy in Heart Failure Patients

In heart failure (HF), the progressive use of multiple drugs and a complex therapeutic regimen is common and is recommended by international guidelines. With HF being a common disease in the elderly, patients often have numerous comorbidities that require additional specific treatment, thus producing a heavy pill burden. Polypharmacy, defined as the chronic use of five or more medications, is an underestimated problem in the management of HF patients. However, polypharmacy has an important impact on HF treatment, as it often leads to inappropriate drug prescription, poor adherence to pharmacological therapies, drug-drug interactions, and adverse effects. The growing complexity of HF patients, whose mean age increases progressively and who present multiple comorbidities, suggests the need for newer models of primary care to improve the management of HF patients. Self-care, telemonitoring, and natriuretic peptide-guided therapy represent promising new HF care models to face the complexity of the disease and its therapeutic regimen.

B-type natriuretic peptide-guided versus symptom-guided therapy in outpatients with chronic heart failure

It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations. The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint). In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio - random effect model: 0.64; 95% confidence interval: 0.43-0.95; P = 0.026). This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials

Background: The role of cardiac natriuretic peptides in the management of patients with chronic Heart Failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. Methods: MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Results: Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type Natriuretic Peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p=0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p=0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p=0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p=0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p=0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p=0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p=0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p=0.142) or all-cause hospitalization (OR:0.726; CI:0.609 to 0.964; p=0.077). Conclusions: Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.

B-type Natriuretic Peptide-guided Chronic Heart Failure Therapy: A Meta-analysis of 11 Randomised Controlled Trials

The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomised controlled trials (RCTs). However, the benefits have been variable. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on all-cause mortality and HF rehospitalisation in patients with chronic HF. We identified RCTs by systematic search of MEDLINE, EMBASE and the Cochrane Controlled Clinical Trials Register Database. Eligible RCTs were those that enrolled more than 40 patients and involved comparison of BNP-guided versus guideline-guided drug therapy of the patients with chronic HF in the outpatient setting. Eleven RCTs with a total of 2414 patients and with a mean duration of 12 months (range, 3-36 months) were included in the meta-analysis. Overall, there was a significantly decreased risk of all-cause mortality (relative risk [RR], 0.83; 95% confidence interval [CI], 0.69-0.99; P=0.035; I(2)=0%) and HF rehospitalisation (RR, 0.75; 95% CI, 0.62-0.91; P=0.004; I(2)=62.2%) in the BNP-guided therapy group. Age, baseline BNP are the major dominants of HF rehospitalisation when analysed using meta-regression. In the subgroup analysis, HF rehospitalisation was significantly decreased in the patients younger than 70 years (RR, 0.45; 95% CI, 0.33-0.61; P=0.000; I(2)=0.0%), or with baseline higher BNP (≥2114pg/mL) (RR, 0.53; 95% CI, 0.39-0.72; P=0.000; I(2)=21.8%). Compared with usual clinical care, B-type natriuretic peptide-guided therapy reduces all-cause mortality and HF rehospitalisation, especially in patients younger than 70 years or with higher baseline BNP.

Natriuretic Peptide-Guided Therapy in Chronic Heart Failure: A Meta-Analysis of 2,686 Patients in 12 Randomized Trials

BackgroundThe role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF.Methodology/Principal FindingsMEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.609 to 0.964; p = 0.077).Conclusions/SignificanceUse of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.

NATRIURETIC PEPTIDE-GUIDED THERAPY IN CHRONIC HEART FAILURE: A META-ANALYSIS OF 2,876 PATIENTS IN 13 RANDOMIZED TRIALS

The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in

T.M.I. (Too Much Information)?

Parents of teenagers will recognize the following scenario: parent comprehensively lecturing teenager on some topic at hand, carefully outlining the rationale for a parental decision, invoking extensive reasoning of why one option is better than another for good adolescent decision-making, etc, etc. Teenager looks away, rolls eyes (possibly, but not necessarily outside of visual field of parent), and mutters, sotto voce , “… T.M.I. ….” Article see p 1719 T.M.I. Too much information. In making clinical decisions, we as clinicians generally believe that more information characterizing our patients' disease processes allows us to make better decisions about therapeutic direction, thereby ultimately improving their quality of life and outcomes. Of course, like many things that we would like to believe, this is not always the case, when the concept is tested rigorously. Over the past few years, several studies have shown that providing an increment of information on which clinicians can base management—compared with management without such information—does not necessarily improve symptoms and/or outcomes. Examples include the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, a randomized trial in which in-hospital management based on invasive hemodynamic information from pulmonary artery catheterization did not improve measures of 6-month outcomes in comparison with clinically based management in decompensated heart failure (HF) patients,1 and the often neutral trial results reported when chronic outpatient HF management is guided according to serial measurements of natriuretic peptide levels, as well.2 The usual trajectory for such studies is initial validation of a marker associated with a pathophysiology of interest, subsequent demonstration of prognostic value in observational studies showing that abnormal levels of the marker are associated with increased risk of an unfavorable outcome, small studies showing that a therapy can improve the marker, and then finally, therapy directed at the marker …

B-Type Natriuretic Peptide–Guided Heart Failure Therapy

The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomized controlled trials (RCTs). However, the benefits of this treatment approach have been uncertain. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on cardiovascular outcomes in patients with chronic HF. We identified RCTs by systematic search of manuscripts, abstracts, and databases. Eligible RCTs were those that enrolled more than 20 patients and involved comparison of BNP-guided drug therapy vs usual clinical care of the patient with chronic HF in an outpatient setting. Eight RCTs with a total of 1726 patients and with a mean duration of 16 months (range, 3-24 months) were included in the meta-analysis. Overall, there was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = .003) in the BNP-guided therapy group compared with the control group. In the subgroup of patients younger than 75 years, all-cause mortality was also significantly lower in the BNP-guided group (RR, 0.52; 95% CI, 0.33-0.82; P = .005). However, there was no reduction in mortality with BNP-guided therapy in patients 75 years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70). The risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64-1.05; P = .12 and RR, 1.07; 95% CI, 0.85-1.34; P = .58, respectively). The additional percentage of patients achieving target doses of angiotensin-converting enzyme inhibitors and beta-blockers during the course of these trials averaged 21% and 22% in the BNP group and 11.7% and 12.5% in the control group, respectively. B-type natriuretic peptide-guided therapy reduces all-cause mortality in patients with chronic HF compared with usual clinical care, especially in patients younger than 75 years. A component of this survival benefit may be due to increased use of agents proven to decrease mortality in chronic HF. However, there does not seem to be a reduction in all-cause hospitalization or an increase in survival free of hospitalization using this approach.