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Tratamiento guiado por el péptido natriurético tipo B para la insuficiencia cardíaca

Appendices

Appendix 1. Search strategies

Cochrane Central Register of Controlled Trials Database [the Cochrane Library, Wiley] (Issue 2 of 12, 2016), Database of Abstracts of reviews of Effectiveness & NHS Economic Evaluation Database [the Cochrane Library, Wiley] (Issue 2 of 4, 2015)

#1

MeSH descriptor: [Heart Failure] this term only

#2

heart failure or chf or hf:ti,ab,kw (Word variations have been searched)

#3

#1 or #2

#4

MeSH descriptor: [Natriuretic Peptide, Brain] explode all trees

#5

b type natriuretic peptide*:ti,ab,kw (Word variations have been searched)

#6

brain natriuretic peptide*:ti,ab,kw (Word variations have been searched)

#7

brain type natriuretic peptide*:ti,ab,kw (Word variations have been searched)

#8

pro bnp:ti,ab,kw (Word variations have been searched)

#9

probnp:ti,ab,kw (Word variations have been searched)

#10

ntpprobnp:ti,ab,kw (Word variations have been searched)

#11

natriuretic peptide type b:ti,ab,kw (Word variations have been searched)

#12

#4 or #5 or #6 or #7 or #8 or #9 or #10 or #11

# 13

MeSH descriptor: [Monitoring, Physiologic] this term only

#14

MeSH descriptor: [Prognosis] this term only

#15

MeSH descriptor: [Treatment Outcome] this term only

#16

monitor*:ti,ab,kw (Word variations have been searched)

#17

((serial or routine or longterm or long term) near/2 (measure* or test* or follow up)):ti,ab,kw (Word variations have been searched)

#18

((guide* or target*) near/2 (therap* or treatment* or pharmacotherap* or strateg*)):ti,ab,kw (Word variations have been searched)

#19

prognos*:ti,ab,kw (Word variations have been searched)

#20

retest*:ti,ab,kw (Word variations have been searched)

#21

#13 or #14 or #15 or #16 or #17 or #18 or #19 or #20

#22

#3 and #12 and #21

Embase (OvidSP)(1974‐14/3/16)

1

Heart Failure/

2

Congestive Heart Failure/

3

(heart failure or hf or chf).tw.

4

1 or 2 or 3

5

brain natriuretic peptide/

6

b type natriuretic peptide*.tw.

7

brain natriuretic peptide*.tw.

8

brain type natriuretic peptide*.tw.

9

bnp*.tw.

10

probnp*.tw.

11

pro bnp*.tw.

12

nt probnp.tw.

13

ntprobnp.tw.

14

natriuretic peptide type b.tw.

15

5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14

16

Patient monitoring/

17

Biologic monitoring/

18

Prognosis/

19

treatment outcome/

20

Follow up/

21

monitor*.tw.

22

((serial or routine or longterm or long term) adj2 (measure* or test* or follow up)).tw.

23

((guide* or target*) adj2 (therap* or treatment* or pharmacotherap* or strateg*)).tw.

24

prognos*.tw.

25

retest*.tw.

26

16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25

27

4 and 15 and 26

28

randomized controlled trial/

29

controlled clinical trial/

30

single blind procedure/ or double blind procedure/

31

crossover procedure/

32

random*.tw.

33

placebo*.tw.

34

((singl* or doubl*) adj (blind* or mask*)).tw.

35

(crossover or cross over or factorial* or latin square).tw.

36

(assign* or allocat* or volunteer*).tw.

37

28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36

38

27 and 37

39

(exp animal/ or nonhuman/) not human/

40

38 not 39

MEDLINE (OvidSP)(1946‐15/3/16)

1

Heart Failure/

2

(heart failure or hf or chf).tw.

3

1 or 2

4

Natriuretic Peptide, Brain/

5

b type natriuretic peptide*.tw.

6

brain natriuretic peptide*.tw.

7

brain type natriuretic peptide*.tw.

8

bnp*.tw.

9

probnp*.tw.

10

pro bnp*.tw.

11

nt probnp.tw.

12

ntprobnp.tw.

13

natriuretic peptide type b.tw.

14

4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13

15

Monitoring, Physiologic/

16

Prognosis/

17

treatment outcome/

18

monitor*.tw.

19

((serial or routine or longterm or long term) adj2 (measure* or test* or follow up)).tw.

20

((guide* or target*) adj2 (therap* or treatment* or pharmacotherap* or strateg*)).tw.

21

prognos*.tw.

22

retest*.tw.

23

15 or 16 or 17 or 18 or 19 or 20 or 21 or 22

24

3 and 14 and 23

25

randomized controlled trial.pt.

26

controlled clinical trial.pt.

27

randomized.ab.

28

placebo.ab.

29

drug therapy.fs.

30

randomly.ab.

31

trial.ab.

32

groups.ab.

33

25 or 26 or 27 or 28 or 29 or 30 or 31 or 32

34

exp animals/ not humans.sh.

35

33 not 34

36

24 and 35

Science Citation Index & Conference Proceedings Citation Index – Science. (ISI Web of Science)(1945 ‐ 15/3/16)

# 1

752,670

TS=("b‐type natriuretic peptide*") OR TS=(btype natriuretic peptide*) OR TS=("b type natriuretic peptide*") OR TS=("type‐b natriuretic peptide*") OR TS=("natriuretic peptide* type‐b") OR TS=("brain natriuretic peptide*") OR TS=("brain type natriuretic peptide*") OR TS=(bnp*) OR TS=(probnp* or "pro bnp*") OR TS=("nt probnp" or ntprobnp) OR TS=("natriuretic peptide type b")

# 2

17,530

TS=(monitor*) OR TS=(((serial OR routine OR longterm OR long term) SAME (measure* or test* or follow up))) OR TS=(((serial OR routine OR longterm OR long term) SAME (measure* or test* or follow up))) OR TS=(prognos*) OR TS=(retest*)

# 3

1,559,464

2 AND 1

# 4

5,037

TS=(((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*)))

# 5

2,233,989

4 AND 3

ClinicalTrials.gov (15/3/16)

Title=natriuretic peptide OR bnp OR pro bnp OR probnp OR ntprobnp OR pro‐bnp OR nt‐probnp

Intervention=natriuretic peptide OR bnp OR pro bnp OR probnp OR ntprobnp OR pro‐bnp OR nt‐probnp

WHO ICTRP (15/3/16)

Title=natriuretic peptide OR bnp OR pro bnp OR probnp OR ntprobnp OR pro‐bnp OR nt‐probnp

Intervention=natriuretic peptide OR bnp OR pro bnp OR probnp OR ntprobnp OR pro‐bnp OR nt‐probnp

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Funnel plot of comparison: NP‐guided versus no NP‐guided treatment for all‐cause mortality.
Figures and Tables -
Figure 4

Funnel plot of comparison: NP‐guided versus no NP‐guided treatment for all‐cause mortality.

'Risk of bias' summary: review authors' judgements about methodological quality for each included study
Figures and Tables -
Figure 2

'Risk of bias' summary: review authors' judgements about methodological quality for each included study

'Risk of bias' graph: review authors' judgements about methodological quality presented as percentages across all included studies.
Figures and Tables -
Figure 3

'Risk of bias' graph: review authors' judgements about methodological quality presented as percentages across all included studies.

Comparison 1 Primary objective BNP vs no BNP, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 1.1

Comparison 1 Primary objective BNP vs no BNP, Outcome 1 All‐cause mortality.

Comparison 1 Primary objective BNP vs no BNP, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 1.2

Comparison 1 Primary objective BNP vs no BNP, Outcome 2 Heart failure mortality.

Comparison 1 Primary objective BNP vs no BNP, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 1.3

Comparison 1 Primary objective BNP vs no BNP, Outcome 3 Heart failure admission.

Comparison 1 Primary objective BNP vs no BNP, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 1.4

Comparison 1 Primary objective BNP vs no BNP, Outcome 4 All‐cause admission.

Comparison 1 Primary objective BNP vs no BNP, Outcome 5 Quality of life.
Figures and Tables -
Analysis 1.5

Comparison 1 Primary objective BNP vs no BNP, Outcome 5 Quality of life.

Comparison 2 Clincal vs UC in primary objectives, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 2.1

Comparison 2 Clincal vs UC in primary objectives, Outcome 1 All‐cause mortality.

Comparison 2 Clincal vs UC in primary objectives, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 2.2

Comparison 2 Clincal vs UC in primary objectives, Outcome 2 Heart failure mortality.

Comparison 2 Clincal vs UC in primary objectives, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 2.3

Comparison 2 Clincal vs UC in primary objectives, Outcome 3 Heart failure admission.

Comparison 2 Clincal vs UC in primary objectives, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 2.4

Comparison 2 Clincal vs UC in primary objectives, Outcome 4 All‐cause admission.

Comparison 2 Clincal vs UC in primary objectives, Outcome 5 Quality of life.
Figures and Tables -
Analysis 2.5

Comparison 2 Clincal vs UC in primary objectives, Outcome 5 Quality of life.

Comparison 3 Subgroup analyses, Outcome 1 All‐cause mortality and age.
Figures and Tables -
Analysis 3.1

Comparison 3 Subgroup analyses, Outcome 1 All‐cause mortality and age.

Comparison 3 Subgroup analyses, Outcome 2 Heart failure admission and age.
Figures and Tables -
Analysis 3.2

Comparison 3 Subgroup analyses, Outcome 2 Heart failure admission and age.

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 4.1

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 1 All‐cause mortality.

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 4.2

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 2 Heart failure mortality.

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 4.3

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 3 Heart failure admission.

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 4.4

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 4 All‐cause admission.

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 5 Quality of life.
Figures and Tables -
Analysis 4.5

Comparison 4 Sensitivity analyses: Outcome blinding, Outcome 5 Quality of life.

Comparison 5 Sensitivity analyses: Attrition, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 5.1

Comparison 5 Sensitivity analyses: Attrition, Outcome 1 All‐cause mortality.

Comparison 5 Sensitivity analyses: Attrition, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 5.2

Comparison 5 Sensitivity analyses: Attrition, Outcome 2 Heart failure mortality.

Comparison 5 Sensitivity analyses: Attrition, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 5.3

Comparison 5 Sensitivity analyses: Attrition, Outcome 3 Heart failure admission.

Comparison 5 Sensitivity analyses: Attrition, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 5.4

Comparison 5 Sensitivity analyses: Attrition, Outcome 4 All‐cause admission.

Comparison 5 Sensitivity analyses: Attrition, Outcome 5 Quality of life.
Figures and Tables -
Analysis 5.5

Comparison 5 Sensitivity analyses: Attrition, Outcome 5 Quality of life.

Comparison 6 Duration of FU BNP vs no BNP, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 6.1

Comparison 6 Duration of FU BNP vs no BNP, Outcome 1 All‐cause mortality.

Comparison 6 Duration of FU BNP vs no BNP, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 6.2

Comparison 6 Duration of FU BNP vs no BNP, Outcome 2 Heart failure mortality.

Comparison 6 Duration of FU BNP vs no BNP, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 6.3

Comparison 6 Duration of FU BNP vs no BNP, Outcome 3 Heart failure admission.

Comparison 6 Duration of FU BNP vs no BNP, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 6.4

Comparison 6 Duration of FU BNP vs no BNP, Outcome 4 All‐cause admission.

Comparison 6 Duration of FU BNP vs no BNP, Outcome 5 Quality of life.
Figures and Tables -
Analysis 6.5

Comparison 6 Duration of FU BNP vs no BNP, Outcome 5 Quality of life.

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 7.1

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 1 All‐cause mortality.

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 2 Heart failure mortality.
Figures and Tables -
Analysis 7.2

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 2 Heart failure mortality.

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 3 Heart failure admission.
Figures and Tables -
Analysis 7.3

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 3 Heart failure admission.

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 4 All‐cause admission.
Figures and Tables -
Analysis 7.4

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 4 All‐cause admission.

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 5 Quality of life.
Figures and Tables -
Analysis 7.5

Comparison 7 Subgroup: BNP vs NT‐proBNP, Outcome 5 Quality of life.

Summary of findings for the main comparison. Does treatment guided by serial BNP or NT‐proBNP monitoring improve outcomes compared to treatment guided by clinical assessment alone?

Does treatment guided by serial BNP or NT‐proBNP monitoring improve outcomes compared to treatment guided by clinical assessment alone?

Patient or population: patients with heart failure
Settings: in‐hospital and out‐of‐hospital
Intervention: serial BNP or NT‐proBNP‐guided treatment
Comparison: no BNP or NT‐proBNP‐guided treament1

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

No BNP or NT‐proBNP‐guided treatment

Serial BNP or NT‐proBNP‐guided treatment

All‐cause mortality
Follow‐up: 3 to 54 months

218 per 1000

190 per 1000
(166 to 220)

RR 0.87
(0.76 to 1.01)

3169
(15 studies)

⊕⊕⊝⊝
low2 ,3

16 studies reported on all‐cause mortality (n = 3292), but only 15 studies are included in the meta‐analysis (n = 3169). For one study data could not be extracted or obtained in a format useable in the review.

Funnel plot analysis suggests possible lack of small studies (beneficial control effect). Insufficient to justify downgrading the quality of evidence.

Heart failure mortality
Follow‐up: 6 ‐ 24 months

91 per 1000

76 per 1000
(49 to 118)

RR 0.84
(0.54 to 1.30)

853
(6 studies)

⊕⊕⊝⊝
low3,4

Heart failure admissions
Follow‐up: 12 ‐ 54 months

377 per 10002

264 per 1000
(230 to 301)

RR 0.70
(0.61 to 0.80)

1928
(10 studies)

⊕⊕⊝⊝
low4,5

All‐cause admissions
Follow‐up: 3 ‐ 54 months

573 per 10002

533 per 1000
(481 to 590)

RR 0.93
(0.84 to 1.03)

1142
(6 studies)

⊕⊕⊝⊝
low3,4

Adverse events
Follow‐up: 9 ‐ 24 months

See comment

See comment

Not estimable

1144
(6 studies)

⊕⊕⊝⊝
low4,6

3/6 studies commented on the difference between the intervention and control groups: no significant difference in one and two favoured the intervention group

Cost
Follow‐up: 12 ‐ 18 months

See comment

See comment

Not estimable

1051
(4 studies)

⊕⊕⊝⊝
low4,7

3/4 studies suggested reduced cost in the intervention groups. One study suggested NP‐guided treatment was unlikely to be cost‐effective.

Quality of life
Scale from: 0 to 105.
Follow‐up: 3 ‐ 54 months

The mean quality of life ranged across control groups from
23 ‐ 34.5 scores

The mean quality of life in the intervention groups was
0.03 lower
(1.18 lower to 1.13 higher)

1812
(8 studies)

⊕⊝⊝⊝
very low4,8,9

Lower score indicates better quality of life

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 The comparisons (controls) fell into two groups: same as the intervention without BNP or NT‐proBNP measures or usual care
2 Allocation concealment was unclear in half of the studies. In two thirds of studies one or both of participants and personnel were not blinded to allocated interventions
3 For all studies (bar one study for all‐cause mortality outcome) the point estimates and confidence intervals include the line of no effect. For all studies (bar two for all‐cause admissions outcome) the point estimates and confidence intervals cross the threshold of appreciable benefit or harm.
4 66% or more of included studies did not blind participants and/or personnel
5 Heterogeneity substantial (I2: 60%, P value: 0.004)
6 Results for adverse events were not consistently reported since data were either first event or multiple events per individual.
7 The outcome measure differed for each study
8 Heterogenity substantial (I2: 75%, P value: 0.0002)
9 95% confidence intervals are greater than 0.5 in either direction

Figures and Tables -
Summary of findings for the main comparison. Does treatment guided by serial BNP or NT‐proBNP monitoring improve outcomes compared to treatment guided by clinical assessment alone?
Table 1. Subgroup data: Setting, NYHA, LVEF (considered post‐hoc)

Study

Participants treated in community or secondary care

Baseline NYHA classification (stages I ‐ IV)

Baseline left ventricular ejection fraction (LVEF, %)

Study inclusion criteria

Intervention group

Control group

Comment in text

Study inclusion criteria

Intervention group (mean, SD unless stated)

Control group (mean, SD unless stated)

Anguita 2010

Hospital

Stage ≥ III

Stage III 73%, IV 27%

Stage III 63%, IV 37%

Not inclusion criterion

44 (18)

46 (18)

Beck‐da‐Silva 2005

Hospital (outpatient)

Stages II ‐ III

2.6 ± 0.7 (mean, SD)

2.4 ± 0.6 (mean, SD)

<40%

23.8 ± 8.8

20.9 ± 9.2

Berger 2010

Hospital & community

Stages III ‐ IV

Not stated

Not stated

<40%

NS

NS

Eurlings 2010

Hospital

Not inclusion criterion

Stage I = 11.5%, II = 64.9%, III = 23.6%

stage I = 9.9%, II = 70.8%, III = 19.3%

Not inclusion criterion

34.9 ± 13.7

36.7 ± 14.8

Januzzi 2011

Hospital

Stages II ‐ IV

Stage II or III = 85.5%

Stage II or III = 84.2%

≤ 40%

28 ± 8.7

25.9 ± 8.3

Jourdain 2007

Hospital (outpatient)

Stages II ‐ III

2.29 ±0.6 (mean, SD)

2.21 ± 0.62 (mean, SD)

<45%

29.9 ± 7.7

31.8 ± 8.4

Karlstrom 2011

Hospital

Stages II ‐ IV

Stage II = 32%, III = 52%, IV = 15%

Stage II = 27%, III = 59%, IV = 14%

<40%

<30% = 57%

<30% = 58%

Krupicka 2010

Hospital

Stages III ‐ IV

2.1 (0.3) (mean, SD)

2.1 (0.3) (mean, SD)

≤ 45%

36.1% (7.2)

32.3% (9.6)

Lainchbury 2010

Hospital & community

Not inclusion criterion

NT‐proBNP group: stage I 12%, II 68%, III 18%, IV 2%

Clinically‐guided group: Stage I 7%, II 66%, III 25%, IV 2%; Usual care: stage I 7%, II 67%, III 25%, IV 1%

Not inclusion criterion though deliberated included patients with preserved LVEF

40 ±15

CG = 39 ± 15, UC = 37 ± 15

Li 2015

Hospital

Stages III ‐ IV

NS

NS

Not inclusion criterion

30 ± 8.1

28 ± 7.9

Maeder 2013

Hospital (outpatient)

Stages ≤ II

49 (83) ≥ III (median, IQR)

53 (83) ≥ III (median, IQR)

'symptoms improved similarly' (at 6 months)

> 45%

56 ± 6

56 ± 7

Persson 2010

Community

Stage II ‐ IV

Stage II 62%, III 38%

Stage II 61%, III 39%

'Improvements in NYHA class and dyspnoea symptoms were seen in both allocation groups, but with no significant differences between the groups'

<50%

31 (9)

33 (7)

Pfisterer 2009

Hospital (outpatient)

Stages ≤ II

186 ≥ III (n)

185 ≥ III (n)

≤ 45%

29.8 (7.7)

29.7 (7.9)

Schou 2013

Hospital

Not inclusion criterion

Stage I ‐ II 86 %

Stage I ‐ II 85 %

<45%

30 (14‐45) median (range)

30 (15‐45) median (range)

Shah 2011

Hospital

Stage III ‐ IV

Authors have no data for baseline NYHA

Authors have no data for baseline NYHA

<35%

20 (15‐25) median (range)

20 (15‐25) median (range)

Shochat 2012

Hospital

Not stated

2.53 (mean)

2.34 (mean)

Not inclusion criterion

23 (6)

23 (7)

Skvortsov 2015

Hospital (outpatient)

Stage III ‐ IV

Stage III 23%, IV 76%

Stage III 26%, IV 74%

At hospital admission

<40%

29.2 (6.1)

29.4 (6.1)

Troughton 2000

Hospital

Stages II ‐ IV

Stage II 72%, overall 2.3 (mean)

Stage II 67%, overall 2.3 (mean)

<40%

28

26

Figures and Tables -
Table 1. Subgroup data: Setting, NYHA, LVEF (considered post‐hoc)
Table 2. Subgroup data: Biomarker target, baseline and change from baseline measurements

Study

Target BNP/NT‐proBNP (pg/mL, unless stated)

Baseline BNP or NT‐proBNP measurement

(units in pg/mL and given as mean (SD), unless stated)

BNP/NT‐proBNP drop (as % of baseline)

(units in pg/mL and given as mean (SD), unless stated)

Biomarker

Study inclusion criteria

Intervention group

Control group

Comment in text

Anguita 2010

100

BNP

No inclusion threshold

57 (77)

65 (97)

No percentage drop reported. BNP at 18 months follow‐up: BNP‐guided group 14 (20); control group 111 (71)

Beck‐da‐Silva 2005

No target set/stated

BNP

No inclusion threshold

502.3 (411.3)

701.6 (409.9)

No percentage drop reported. BNP at follow‐up: control arm 626.8 (325.8); BNP arm 477.8 (406.9)

Berger 2010

< 2200 NT = proBNP (reported in IPD analysis by Troughton 2014)

NT‐proBNP

No inclusion threshold

2216 (355‐9649) mean (95% CI)

Multidisplinary care 2469 (355 ‐18487; Usual care 2359 (355 ‐15603) mean (95% CI)

No percentage drop reported. NT ‐proBNP change from baseline to FU graphically shown in Berger 2010 (Figure 4). Decrease in NT‐proBNP more apparent in NT‐proBNP‐guided group than multidisplinary group. No decrease in usual care group

Eurlings 2010

Set individually for each participant as the lowest level at discharge or at 2 weeks follow‐up

NT‐proBNP

NT‐proBNP levels at admission: minimum 1,700 pg/ml. Additionally NT‐proBNP levels during hospitalisation, defined as a decrease of more than 10%, with a drop in NT‐proBNP levels of at least 850 pg/ml, from admission to discharge.

2961 (1383 ‐ 5144) median (IQR)

2936 (1291‐5525) median (IQR)

Outcome data available by subgroup baseline BNP (above or below discharge NT‐proBNP 2950 pg/ml)

No percentage drop reported. Median (IQR) at 12 months follow‐up: NT‐proBNP‐guided group ‐432 (‐1392 to 297); Clincially‐guided group ‐572 (‐1329 to 434).

Januzzi 2011

≤ 1000

NT‐proBNP

No inclusion threshold

2344 (median)

1946 (median)

No percentage drop reported. Median NT‐proBNP at follow‐up: Standard care group 1844 (P = 0.61 follow‐up vs baseline); NT‐proBNP‐guided group 1125 (P = 0.01 vs baseline)

Jourdain 2007

< 100

BNP

No inclusion threshold

352 (260) mean (SD)

Not measured

No percentage drop reported. BNP‐guided group only shown graphically in Jourdain 2007 (figure 5): mean BNP level drops over time and % of patients achieving target increases.

Karlstrom 2011

<150 ng/L in patients under 75; <300 ng/L in patients over 75 yrs

BNP

No inclusion threshold

808.2 (676.1) ng/L, mean (SD)

898.9 (915.3 ng/L, mean (SD)

No percentage drop reported. BNP at follow‐up: control group 457 (603), BNP‐guided group 403 (468)

Krupicka 2010

<100

BNP

No inclusion threshold

704 (228‐2852) median (range)

633 (276‐3756) median (range)

No percentage drop reported. In the BNP group 90% of patients manage to reduce BNP to <400 pg/mL; of this 90%, 2/3 of patients to achieve <100 pg/mL. Email from author "We do not have BNP values of the Clinical group at the end of follow‐up. Median BNP value after 6 months in BNP group was 235pg/ml. (At hospital discharge 704pg/ml; after 1 month 328.5pg/ml; after 3 months 253pg/ml)."

Lainchbury 2010

< 150 µmol/L

NT‐proBNP

No inclusion threshold

2012 (516‐10233) median (IQR)

Clinically‐guided group: 1996 (425‐6588); Usual care: 2012 (425‐10571) median (IQR)

No percentage drop reported. No follow‐up data. Comment in text 'Plasma NT‐proBNP levels fell similarly within 6 months of randomisation in both the NT‐proBNP and CG groups (by 20% and 23%, respectively; P 0.001)'.

Li 2015

50% of basal level or < 300

BNP

No inclusion threshold

1167.8 (219.9) mean (SD)

1145.8 (224.9) mean (SD)

No percentage drop reported. Change in BNP level shown in Figure 2 (Li 2015). 'BNP value decreased dramatically over the duration of medication, but there was no difference between the two groups.'

Maeder 2013

< 400 in patients younger than 75 years; < 800 in patients aged 75 years or older

NT‐proBNP

N‐terminal BNP level of 400 pg/mL or higher in patients younger than 75 years and a level of 800 pg/mL or higher in patients aged 75 years or older

2210 (1514‐4081) ng/L, median (IQR)

2191 (1478‐4890) ng/L, median (IQR)

Maeder 2013 reports: 'NT‐proBNP was reduced similarly in patients allocated to NT‐proBNP‐guided or symptom‐guided management. The proportion of patients with NT‐proBNP below the target was low throughout the study period and did not significantly differ between groups (Figure 2C) although it tended to be lower in the NT‐proBNP‐guided group.

Persson 2010

At least a 50% reduction from baseline NT‐proBNP

NT‐proBNP

Elevated NT‐proBNP levels (males > 800 ng/L, females > 1000 ng/L)

2661 (2.1) ng/L, geometric mean(coefficient of variation, %)

2429 (2.1) ng/L, geometric mean(coefficient of variation, %)

No percentage drop reported. Geometric Mean (SD) at follow‐up: NT‐proBNP‐guided group ‐ 301 ng/L to 2360 ng/L; control group ‐362 ng/L to 2067 ng/L. Comment in text 'similar modest decrease ( 10%) in NT‐proBNP from baseline to end‐of study was observed in both groups……NT‐proBNP levels were reduced by .50% in 24 (19%) and 27 (22%), of patients with and without NT‐proBNP‐guided treatment, respectively'.

Pfisterer 2009

< 400 in patients younger than 75 years; < 800 in patients aged 75 years or older

NT‐proBNP

N‐terminal BNP level of 400 pg/mL or higher in patients younger than 75 years and a level of 800 pg/mL or higher in patients aged 75 years or older

3998 (2075‐7220) median (IQR)

4657 (2455‐7520) median (IQR)

No percentage drop reported. No follow‐up data. Pfisterer 2009 (figure 3b) graphically shows data for NT‐proBNP changes over 6 months (by age). Comment in text 'There were no significant differences between the 2 treatment groups by by N‐terminal BNP level (P=.06 vs P=.30).'

Schou 2013

No target set/stated

NT‐proBNP

NT‐proBNP ≥ 1000 pg/mL after up‐titration (i.e. at the randomisation visit)

1884 (1033‐10435) average statistic not stated)

2042 (1023‐9668) average statistic not stated

No percentage drop reported. Change in NT‐proBNP during follow‐up: NT‐proBNP‐guided group ‐129 (‐722 to 674) median (IQR); Clinically managed group ‐26 (‐681 to 751) median (IQR). Comment in text: 'Patients in whom NT‐proBNP increased ≤ 30% during the follow up period had a higher frequency of admission (69% vs. 47%, P = 0.002), a higher number of admission days (median) (14 days vs. 5 days, P= 0.003), a higher number of admissions (median) (2 vs. 1, P = 0.009), a lower quality of life (mean difference) (6 points, P = 0.032), and a poorer functional class (37% vs. 18% in functional class III–IV, P = 0.001).'

Shah 2011

Discharge BNP

BNP

No inclusion threshold

453 (221‐1135) median (IQR)

440 (189 ‐981) median (IQR)

No percentage drop reported. Median (IQR) BNP at follow‐up: BNP‐guided group 412.5 (111,894); control (congestion score) group 471 (235.5, 1180)

Shochat 2012

No target set/stated

NT‐proBNP

Email from author confirmed 'NT‐ProBNP > 2000 at day of randomisation'

5868 (2532)

5820 (2434)

No percentage drop reported.

Skvortsov 2015

<1000 pg/mL or at least 50% reduction from baseline NT‐proBNP at discharge

NT‐proBNP

> 1400 pg/mL at hospital admission

3750 (2224‐ 6613)

median (IQR)

2783.0 (2021.5‐ 4827.5)

median (IQR)

At hospital discharge

At 6 months:

NT‐proBNP‐guided group: 53% (Median drop (QR): 1585.5 (976.6, 2742.5))

Control group: 10.2% (median (IQR): 2189.0 (1954.0, 3688.5))

Troughton 2000

200 µmol/L

NT‐proBNP

No inclusion threshold

217 µmol/L, mean

251 µmol/l, mean

No percentage drop reported. At 6 months follow‐up: Nt‐proBNP‐guided group decreased by 79 pmol/L, mean; clinically‐guided group decreased by 3 pmol/L, mean (P = 0.16)

Figures and Tables -
Table 2. Subgroup data: Biomarker target, baseline and change from baseline measurements
Table 3. Adverse event data

Study

Adverse events

Participants (N)

Missing participants (N)

Number of adverse events (definitions not

consistent or not stated; not clear whether first event per participant or every event)

Additional data either from published articles or supplied by author

Intervention group

Control group

Total

Intervention group

Control group

Total

Intervention

group

Control

group

Total

Januzzi 2011

75

76

151

6

6

12

30

23

53

No significant differences between groups.

No specific event showed a significant difference between groups

Events in intervention group: Abdominal pain (1); acute renal failure (4); anaemia (1); atrial fibrillation (2); cough (2); diarrhoea (2); dizziness (5); fever (1); gastrointestinal bleeding (1); hyper/hypokalaemia (3); hypotension (4); respiratory infection (2); syncope(2)

Events in control group: Abdominal pain (1); acute renal failure (3); anaemia (0); atrial fibrillation (5); cough (1); diarrhoea (1); dizziness (4); fever (1); gastrointestinal bleeding (1); hyper/hypokalaemia (1); hypotension (0); respiratory infection (4); syncope(1)

Krupicka 2010

26

26

52

0

0

0

7

0

7

Email from author 17.10.14 confirmed: Hyperkalaemia (n = 2); orthostatic hypotension (n = 2); bradycardia (n = 3)

Maeder 2013

59

64

123

12

12

24

Not reported

Not reported

66

Maeder 2013 reported: "58% of the patients in the NT‐proBNP‐guided and 50% in the symptom‐guided group had at least one SAE (p=0.32). SAE’s related to renal failure (14% versus 2%, p=0.01) were more common in the NT‐proBNP‐guided group, whereas hypotension tended to be less common (0% versus 8%, p=0.06)." No additional information

Persson 2010

126

124

250

8

7

15

42

39

81

No additional information provided

Pfisterer 2009

251

248

499

32

29

61

123

113

236

P = 0.47

Renal impairment: intervention group n = 4, control group n = 5 (P = 0.64)

Hypotension: intervention group n = 6, control group n = 3 (P = 0.22)

No other type of adverse event described.

Adverse events ≥ 75 years old patients: intervention group 10.5% vs control group 5.5% (P = 0.12)

Adverse events in < 75 years old patients: intervention group 3.7% vs. control group 4.9% (P = 0.74)

Troughton 2000

33

36

69

0

0

0

13

9

22

P = 0.32

No additional information provided

Figures and Tables -
Table 3. Adverse event data
Table 4. Sensitivity Analyses

Outcome

Studies(N)

Participants (n)

Risk ratio

95% Confidence intervals

Outcome blinding (low risk of bias studies only)

Analysis 4.1

All‐cause mortality

5

1663

0.94

0.80 to 1.11

Analysis 4.2

Heart failure mortality

1

268

1.20

0.66 to 2.20

Analysis 4.3

Heart failure admission

4

1318

0.83

0.71 to 0.98

Analysis 4.4

All‐cause admission

2

675

0.98

0.88 to 1.10

Analysis 4.5

Quality of life

3

994

‐0.01

‐1.28 to 1.27

Incomplete data (low risk of bias studies only)

Analysis 5.1

All‐cause mortality

7

1229

0.83

0.65 to 1.07

Analysis 5.2

Heart failure mortality

4

533

0.52

0.26 to 1.03

Analysis 5.3

Heart failure admission

5

814

0.63

0.49 to 0.81

Analysis 5.4

All‐cause admission

4

833

0.94

0.83 to 1.07

Analysis 5.5

Quality of life

3

534

‐0.57

‐1.92 to 0.78

Figures and Tables -
Table 4. Sensitivity Analyses
Table 5. Agreements and disagreements with other reviews

Outcome

Review

Number of RCTs

N

Summary measure (hazard ratio HR,

risk ratio RR, odds ratio OR,

weighted mean difference WMD)

95% Confidence intervals

p‐value

Heterogeneity (I2)

All‐cause mortality (all patients)

Felker 2009

6

1627

HR

0.69

0.55 to 0.86

Not reported

Not reported

Porapakkham 2010

8

1726

RR

0.76

0.63 to 0.91

0.003

Not reported

Li 2013

11

2414

RR

0.83

0.69 to 0.99

0.0.35

0%

Savarese 2013

12

2686

OR

0.74

0.6 to 0.91

0.005

0%

Li 2014

Not reported

Not reported

RR

0.79

0.67 to 0.92

0.004

Not reported

Troughton 2014

10

2280

HR

0.82

0.67 to 1.00

0.05

0%

Xin 2015

14

3004

RR

0.94

0.81 to 1.08

0.39

3%

This review

15

3169

RR

0.87

0.76 to 1.01

0.06

16%

Heart failure admission

Li 2013

7

1190

RR

0.65

0.5 to 0.84

0.001

52.30%

Savarese 2013

8

1920

OR

0.55

0.4 to 0.77

<0.0001

58.20%

Li 2014

Not reported

Not reported

RR

0.67

0.46 to 0.97

0.03

Not reported

Troughton 2014

11

2431

HR

0.74

0.60 to 0.90

0.002

24.00%

Xin 2015

11

2572

RR

0.79

0.63 to 0.98

0.03

67.00%

This review

10

1928

RR

0.7

0.61 to 0.80

<0.0001

60.00%

All‐cause admission

Porapakkham 2010

3

330

RR

0.82

0.64 to 1.05

0.12

Not reported

Savarese 2013

5

1108

OR

0.8

0.63‐ 1.02

0.077

0%

Xin 2015

7

1627

RR

0.97

0.89 to 1.07

0.56

8%

This review

6

1142

RR

0.93

0.84 to 1.03

0.15

0%

Adverse events

Li 2014

Not reported

Not reported

RR

1.15

0.99 to 1.342

0.69

Not reported

Adverse events (symptomatic hypotension)

Xin 2015

4

838

RR

1.72

0.59 to 5.05

0.32

43%

Adverse events (hyper/hypokalemia)

Xin 2015

2

354

RR

1.34

0.42 to 4.34

0.62

0%

Adverse events (renal dysfunction)

Xin 2015

3

769

RR

1.46

0.34 to 6.24

0.21

0%

Adverse events (severe cough)

Xin 2015

2

220

RR

1.93

0.69 to 5.37

0.21

0%

Quality of life

Xin 2015

5

1172

WMD

‐1.29

‐3.81 to 1.22

0.31

49%

This review

8

1812

WMD

‐0.03

‐1.18 to 1.13

0.97

75%

Figures and Tables -
Table 5. Agreements and disagreements with other reviews
Table 6. Subgroup agreements and disagreements with other reviews

Outcome

Review

Number of RCTs

N

Summary measure (hazard ratio HR,

risk ratio RR, odds ratio OR, weighted

mean difference WMD)

95%

Confidence intervals

P value

Heterogeneity (I2)

All‐cause mortality (< 75 years)

Porapakkham 2010

2

741

RR

0.52

0.33 to 0.82

0.005

Not reported

This review

3

420

RR

0.73

0.49 to 1.10

0.13

58%

All‐cause mortality (> 75 years)

Porapakkham 2010

2

741

RR

0.94

0.71 to 1.25

0.7

Not reported

This review

3

410

RR

1.23

0.96 to 1.57

0.1

58%

All‐cause mortality (< 72 years)

Xin 2015

7

Not reported

RR

0.82

0.58 to 1.17

Not reported

0%

All‐cause mortality (≥ 72 years)

Xin 2015

7

Not reported

RR

0.96

0.83 to 1.13

Not reported

24%

Heart failure admission (<70 years)

Li 2013

Not reported

Not reported

RR

0.45

0.33 to 0.61

< 0.0001

0%

Li 2014

Not reported

Not reported

RR

0.44

0.31 to 0.63

Not reported

Not reported

Heart failure admission (>70 years)

Li 2013

Not reported

Li 2014

Not reported

Not reported

RR

0.89

0.74 ‐ 1.07

Not reported

Not reported

All‐cause admission (< 72 years)

Xin 2015

5

Not reported

RR

0.61

0.41 to 0.93

Not reported

65%

All‐cause admission (≥ 72 years)

Xin 2015

6

Not reported

RR

0.95

0.79 to 1.14

Not reported

38%

All‐cause admission (< 72 years)

Xin 2015

4

Not reported

RR

0.88

0.77 to 1.00

Not reported

0%

Figures and Tables -
Table 6. Subgroup agreements and disagreements with other reviews
Comparison 1. Primary objective BNP vs no BNP

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

3169

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.76, 1.01]

2 Heart failure mortality Show forest plot

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.30]

3 Heart failure admission Show forest plot

10

1928

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.61, 0.80]

4 All‐cause admission Show forest plot

6

1142

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.03]

5 Quality of life Show forest plot

8

1812

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐1.18, 1.13]

Figures and Tables -
Comparison 1. Primary objective BNP vs no BNP
Comparison 2. Clincal vs UC in primary objectives

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

3169

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.76, 1.01]

1.1 Clinical assessment

15

2850

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.76, 1.04]

1.2 Usual care

2

319

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.56, 1.13]

2 Heart failure mortality Show forest plot

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.30]

2.1 Clinical assessment

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.30]

2.2 Usual care

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Heart failure admission Show forest plot

10

1928

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.61, 0.80]

3.1 Clinical assessment

10

1609

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.60, 0.81]

3.2 Usual care

2

319

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.53, 0.99]

4 All‐cause admission Show forest plot

6

1142

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.03]

4.1 Clinical assessment

6

1142

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.03]

4.2 Usual care

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Quality of life Show forest plot

8

1812

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐1.18, 1.13]

5.1 Clincial assessment

8

1812

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐1.18, 1.13]

5.2 Usual care

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 2. Clincal vs UC in primary objectives
Comparison 3. Subgroup analyses

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality and age Show forest plot

3

830

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.27]

1.1 Equal or greater than 75 yrs old

3

410

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.96, 1.57]

1.2 Under 75 yrs old

3

420

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.49, 1.10]

2 Heart failure admission and age Show forest plot

1

365

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.69, 1.25]

2.1 Equal or greater than 75 yrs old

1

188

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.77, 1.64]

2.2 Under 75 yrs old

1

177

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.45, 1.17]

Figures and Tables -
Comparison 3. Subgroup analyses
Comparison 4. Sensitivity analyses: Outcome blinding

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

1663

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.80, 1.11]

2 Heart failure mortality Show forest plot

1

268

Risk Ratio (M‐H, Fixed, 95% CI)

1.2 [0.66, 2.20]

3 Heart failure admission Show forest plot

4

1318

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.98]

4 All‐cause admission Show forest plot

2

675

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.88, 1.10]

5 Quality of life Show forest plot

3

994

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐1.28, 1.27]

Figures and Tables -
Comparison 4. Sensitivity analyses: Outcome blinding
Comparison 5. Sensitivity analyses: Attrition

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

7

1229

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.65, 1.07]

2 Heart failure mortality Show forest plot

4

533

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.26, 1.03]

3 Heart failure admission Show forest plot

5

814

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.49, 0.81]

4 All‐cause admission Show forest plot

4

833

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.83, 1.07]

5 Quality of life Show forest plot

3

534

Mean Difference (IV, Fixed, 95% CI)

‐0.57 [‐1.92, 0.78]

Figures and Tables -
Comparison 5. Sensitivity analyses: Attrition
Comparison 6. Duration of FU BNP vs no BNP

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

3169

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.76, 1.01]

1.1 ≤ 1 yr

5

555

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.25, 0.85]

1.2 1‐2 yrs

8

1842

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.69, 0.99]

1.3 > 2 yrs

2

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.87, 1.41]

2 Heart failure mortality Show forest plot

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.30]

2.1 ≤ 1 yr

3

313

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.28, 1.48]

2.2 1 ‐ 2 yrs

3

540

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.56, 1.57]

2.3 > 2 yrs

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Heart failure admission Show forest plot

10

1928

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.61, 0.80]

3.1 ≤ 1 yr

3

278

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.23, 0.58]

3.2 1 ‐ 2 yrs

5

878

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.54, 0.79]

3.3 > 2 ys

2

772

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.77, 1.23]

4 All‐cause admission Show forest plot

6

1142

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.03]

4.1 ≤ 1 yr

3

247

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.58, 1.07]

4.2 1 ‐ 2 yrs

2

488

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.77, 1.03]

4.3 > 2 yrs

1

407

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.89, 1.21]

5 Quality of life Show forest plot

8

1812

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐1.18, 1.13]

5.1 ≤ 1 yr

5

561

Mean Difference (IV, Fixed, 95% CI)

‐3.14 [‐6.46, 0.19]

5.2 1 ‐ 2 yrs

2

844

Mean Difference (IV, Fixed, 95% CI)

1.98 [‐0.76, 4.72]

5.3 > 2 yrs

1

407

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐1.38, 1.38]

Figures and Tables -
Comparison 6. Duration of FU BNP vs no BNP
Comparison 7. Subgroup: BNP vs NT‐proBNP

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

3169

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.76, 1.01]

1.1 NT‐proBNP

9

2391

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.75, 1.01]

1.2 BNP

6

778

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.62, 1.28]

2 Heart failure mortality Show forest plot

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.30]

2.1 NT‐proBNP

2

127

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.08, 1.19]

2.2 BNP

4

726

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.61, 1.56]

3 Heart failure admission Show forest plot

10

1928

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.53, 0.84]

3.1 NT‐proBNP

6

1328

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.48, 0.89]

3.2 BNP

4

600

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.43, 1.05]

4 All‐cause admission Show forest plot

6

1142

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.03]

4.1 NT‐proBNP

2

476

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.85, 1.14]

4.2 BNP

4

666

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.77, 1.01]

5 Quality of life Show forest plot

8

1812

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐1.18, 1.13]

5.1 NT‐proBNP

7

1771

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐1.19, 1.14]

5.2 BNP

1

41

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐15.30, 14.90]

Figures and Tables -
Comparison 7. Subgroup: BNP vs NT‐proBNP