TY - JOUR
T1 - B-type natriuretic peptide-guided therapy for heart failure (HF)
T2 - a systematic review and meta-analysis of individual participant data (IPD) and aggregate data
AU - Pufulete, Maria
AU - Maishman, Rachel
AU - Dabner, Lucy
AU - Higgins, Julian P T
AU - Rogers, Chris A
AU - Dayer, Mark
AU - MacLeod, John
AU - Purdy, Sarah
AU - Hollingworth, William
AU - Schou, Morten
AU - Anguita-Sanchez, Manuel
AU - Karlström, Patric
AU - Shochat, Michael Kleiner
AU - McDonagh, Theresa
AU - Nightingale, Angus K
AU - Reeves, Barnaby C
PY - 2018/7/31
Y1 - 2018/7/31
N2 - Background: We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). Methods: Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. Results: We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53-0.92, patients < 75 years old and HR 1.07, 95% CI 0.84-1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71-0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83-2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). Conclusion: BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear. Systematic review registration: PROSPERO CRD42013005335
AB - Background: We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). Methods: Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. Results: We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53-0.92, patients < 75 years old and HR 1.07, 95% CI 0.84-1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71-0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83-2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). Conclusion: BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear. Systematic review registration: PROSPERO CRD42013005335
KW - Cause of Death
KW - Heart Failure/drug therapy
KW - Hospitalization
KW - Humans
KW - Mortality
KW - Natriuretic Peptide, Brain/blood
KW - Quality of Life
KW - Randomized Controlled Trials as Topic
U2 - 10.1186/s13643-018-0776-8
DO - 10.1186/s13643-018-0776-8
M3 - Journal article
C2 - 30064502
SN - 2046-4053
VL - 7
JO - Systematic Reviews
JF - Systematic Reviews
M1 - 112
ER -
