This was assessed as directly applicable with minor limitations. 8.2 Monitoring using repeated biomarker measurement or imaging for management of chronic heart failure in people who also have chronic kidney disease Biomarkers are substances measurable in the blood stream which can be used to diagnose and monitor disease. Chronic kidney disease (CKD) develops when damage to the kidney results in reduced function. The extent of this damage can be approximated by blood tests to estimate glomerular filtration rate (GFR) from the kinetics of a stable excreted substance e.g. creatinine and a urine test to detect renal leakage of protein- usually albumin. The management of CKD is covered by NICE guideline CG182. Natriuretic peptides and troponin are raised in patients with HF and could potentially be used to guide treatment. However renal function can affect the level of biomarkers in the blood principally by affecting their clearance and this effect could influence their interpretation of biomarker results by clinicians. Imaging with echocardiography or cardiac MRI could be an alternative method of monitoring. The aim of this section of the review is to examine the clinical and cost-effectiveness of biomarker measurement or imaging in the management of heart failure in patients with CKD. 8.2.2 Review question: What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have CKD? For full details see review protocol in Appendix A. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Table 84: PICO characteristics of review question Population People diagnosed with heart failure in a community or outpatient setting who also have chronic kidney disease Aged under 75 years Aged 75 and over. Interventions Biomarker monitoring: serial (protocol-driven) measurements of circulating biomarker concentration: NT-proBNP (alone) BNP (alone) Troponin (alone) Combination of 2 biomarkers Combination of all 3 biomarkers Imaging monitoring: serial (protocol-driven) cardiac MRI Imaging monitoring: serial (protocol-driven) echocardiography Comparisons Each other Usual care: Clinical monitoring (protocol-driven) Usual care: Clinical monitoring (not protocol-driven) Outcomes CRITICAL Mortality (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all-cause) (Count rate) IMPORTANT Adverse events - hypotension (Dichotomous) Adverse events - hyperkalaemia (Dichotomous) Adverse events - renal function (Continuous) Adverse events - bradycardia (Dichotomous) Adverse events - arrhythmic events (Dichotomous) Study design Systematic reviews of RCTs RCTs 8.2.3 Clinical evidence A search was conducted for randomised trials and systematic reviews of randomised trials comparing the effectiveness of monitoring with repeated biomarker measurement (BNP, NT-proBNP or troponin) or repeated cardiac imaging (echocardiography or cardiac MRI), compared to usual care without repeated measurement or imaging, that had a population or subgroup with chronic kidney disease. Subgroup analyses in one primary study 114 and one systematic review 55, 338 , including an individual patient data meta-analysis of seven studies, were included in the review. These are summarised in Table 85 and Table 86, and the clinical evidence is summarised in Table 87. See also the study selection flow chart in Appendix C, forest plots in Appendix E, study evidence tables in Appendix F, GRADE tables in Appendix H and excluded studies list in Appendix I. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 All of the studies involved repeated BNP or NT-proBNP (together called NP) biomarker testing. Treatment algorithms varied, with some treating to an absolute target, others aiming for a personal target best on percentage drop of levels. These were compared against clinical monitoring in the other study arm. No relevant studies comparing usual care with routine cardiac imaging, troponin, or combinations of different biomarkers were identified. Table 85: Summary of systematic review included in the review Study Intervention and comparison (in HF clinic unless stated otherwise) Population Included data Troughton (Brunner-la ) Troughton IPD NP-guided therapy vs Clinically-guided therapy (3-24 months) Stratified by LVEF status. Age mean (SD): Studies included in IPD: BATTLESCARRED, Berger 2010, Christchurch pilot, PRIMA, PROTECT, SIGNAL-HF, TIME- CHF*, UPSTEP *the HFpEF arm of TIME-CHF is included in Brunner La Rocca, but not the original meta-analysis ACEi/ARB: Angiotensin converting enzyme inhibitor and/or Aldosterone receptor blocker, BB: Beta-blocker, IV: Intravenous therapy, NP: natriuretic peptides including BNP and NT-proBNP Table 86: Summary of primary studies included in the review Study Intervention and comparison (in HF clinic unless stated otherwise) Population Outcomes Comments BATTLESCARRE D trial: Lainchbury (Lainchbury ) NP monitoring: Therapy increased to achieve clinical and NP target (congestion score<2 Clinical monitoring: Therapy increased to meet target months No protocol: Discharged to primary care Age > 18 mean: HF-admission Elevated NP (NT- proBNP > 50 pmol/L) Troughton IPD: Mortality Recruited from hospital Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison (in HF clinic unless stated otherwise) Population Outcomes Comments (Adlbrecht ) NP monitoring: Therapy intensified to meet or maintain target (NT-proBNP <2200pg/l), Clinical monitoring: Therapy intensified at clinician s discretion according to clinical assessment No protocol: Discharged to primary care Age mean: 71(12) Recently hospitalised with NYHA class III/IV and cardiothoracic ratio > 0.5 or LVEF Troughton IPD: Mortality Recruited from hospital Christchurch pilot Troughton NP monitoring: Treatment intensified to reach target (NT- Clinical monitoring: Therapy increased to reach target (Framingham score <2) Age mean: 70(10) LVEF < 40%, NYHA class II-IV Treatment with at least ACEi and loop diuretic Troughton IPD: Mortality Recruited in hospital or HF clinic PRIMA trial: NP monitoring: therapy increased to reach or maintain target (NT-proBNP at the lowest level recorded at discharge or two weeks following), 24 months Clinical monitoring: Therapy increased at clinician s discretion according to clinical assessment, 24 months Age mean: 72(12) Recent HF- admission, mainly NYHA III, Elevated NPs (NT- proBNP levels at admission 1700 pg/mL) that respond to treatment (decrease 10% at discharge) Troughton IPD: Mortality Primary paper: Admissions (as days in hospital) Recruited from hospital PROTECT trial: (Weiner , Mallick , Ibrahim , Bhardwaj ) NP monitoring: Therapy intensified to reach target (NT- months Clinical monitoring: Therapy intensified at clinician discretion according to clinical assessment, 6-12 months Age 21 years, NYHA class II-IV, LVEF 40%, destabilisation in (attended hospital or clinic for worsening HF) Troughton IPD: Mortality Recruited Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison (in HF clinic unless stated otherwise) Population Outcomes Comments SIGNAL-HF trial: NP monitoring (in primary care): Treatment increased to achieve target (NT-proBNP reduction of 50% from baseline), 9 months Clinical monitoring (in primary care): Therapy increased at clinician s discretion according to clinical assessment, 9 months Age mean: 78(7) NYHA class II-IV, LVEF < 50%, stable in primary care Elevated NPs (NT- proBNP levels males > 800, females > 1000 ng/L) Troughton IPD: Mortality Recruited from primary TIME-CHF trial: (Pfisterer , Brunner-la , Sanders-van , Sanders-van , Kaufmann ) NP monitoring: Therapy intensified to reach BNP target n=251 with rEF, 59 with pEF Clinically monitoring: Therapy intensified to reach target (NYHA II), 18 months n=248 with rEF, 64 with pEF Age 60 years, NYHA class II with current therapy, HF admission in the last year, elevated NPs (NT- proBNP of 400pg/mL if < pg/mL if 75y) Stratified by LVEF status Troughton IPD: Mortality* Recruited from multiple centres in Switzerlan d and Germany ACEi/ARB: Angiotensin converting enzyme inhibitor and/or Aldosterone receptor blocker, BB: Beta-blocker, IV: Intravenous therapy, NP: natriuretic peptides including BNP and NT-proBNP Monitoring Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Table 87: Clinical evidence summary: NP monitoring versus clinical monitoring in people who also have chronic kidney disease Outcomes No of Participant s (studies) Follow up Quality of the evidence (GRADE) Relativ e effect CI) Anticipated absolute effects Risk with Clinical monitoring Risk difference with NP monitoring All-cause mortality 1147 months VERY LOW b,c,e due to risk of bias, imprecision, inconsistency Approximatea (from 105 fewer to 172 more) All-cause hospitalisation (days in hospital) VERY LOWb,c,d due to risk of bias, imprecision, indirectness The mean all-cause hospitalisation (days in hospital) in the control group was 6.54 days in hospital The mean all-cause hospitalisation (days in hospital) in the intervention groups was (2.81 lower to 3.57 higher) a Control group risk not available, approximated from risk for both arms combined, will under-estimate effect b Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias c Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs d Downgraded by 1 increment for indirectness as proxy for the protocol outcome of rate ratio of all-cause admissions e Downgraded by 1 increment as point estimates were inconsistent, not enough studies to perform subgroup analysis, I2 Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 8.2.4 Economic evidence Published literature No previously published economic evidence was identified for this question in the review. See also the health economic study selection flow chart in Appendix D. 8.2.5 Evidence statements Clinical Subgroup analyses in one primary study and one systematic review (which included an IPD meta- analysis of seven studies) were identified for inclusion within the review. All of the included studies compared repeated biomarker measurement (BNP or NT-proBNP) with clinical monitoring in people with HF who also have CKD. The quality of the evidence was very low as a result of risk of bias, imprecision due to wide confidence intervals surrounding the effect estimate, indirectness of the outcome and inconsistency due to heterogeneity in the results reported by individual studies. Mortality did not demonstrate a clear effect with the confidence interval ranging from a decrease and increase in all-cause mortality.The outcome all-cause hospitalisations (as measured by days in hospital) suggested no clinical effect of NP monitoring. Economic No economic evaluations were identified. 8.3 Monitoring using repeated biomarker measurement or imaging for management of chronic heart failure in people who also have atrial fibrillation Atrial fibrillation (AF) is an abnormal heart rhythm affecting 2-3% of the adult population but is more common in patients with HF. Patients may be aware of palpitations, fatigue or breathlessness although many are asymptomatic. AF may be detected on examination, with an irregular pulse, and confirmed by ECG. The treatment of AF includes rate and rhythm control as well as anticoagulation to reduce the stroke risk. The management of AF is covered by NICE guideline CG180. Biomarkers are substances measurable in the blood stream which can be used to diagnose and monitor disease. Natriuretic peptides are released from the myocardium in response to fluid overload. The two main natriuretic peptides used in clinical practice are amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP). Troponin is released in response to myocardial injury. Natriuretic peptides and troponin are raised in patients with HF and could potentially be used to guide treatment however AF can affect the level of these biomarkers by affecting their physiology of their secretion into the blood and also potentially affect their clearance thus affecting the ability of clinicians to interpret their results. Imaging with echocardiography or cardiac MRI could be an alternative method of monitoring. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 The aim of this section of the review is to examine the clinical and cost-effectiveness of biomarker measurement or imaging in the management of heart failure in patients with AF. 8.3.2 Review question: What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have atrial fibrillation? For full details see review protocol in Appendix A. Table 88: PICO characteristics of review question Population People diagnosed with heart failure in a community or outpatient setting who also have atrial fibrillation Aged under 75 years Aged 75 and over. Interventions Biomarker monitoring: serial (protocol-driven) measurements of circulating biomarker concentration: NT-proBNP (alone) BNP (alone) Troponin (alone) Combination of 2 biomarkers Combination of all 3 biomarkers Imaging monitoring: serial (protocol-driven) cardiac MRI Imaging monitoring: serial (protocol-driven) echocardiography Comparisons Each other Usual care: Clinical monitoring (protocol-driven) Usual care: Clinical monitoring (not protocol-driven) Outcomes CRITICAL Mortality at during study (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all-cause) (Count rate) IMPORTANT Adverse events - hypotension (Dichotomous) Adverse events - hyperkalaemia (Dichotomous) Adverse events - renal function (Continuous) Adverse events - bradycardia (Dichotomous) Adverse events - arrhythmic events (Dichotomous) Study design Systematic reviews of RCTs RCTs 8.3.3 Clinical evidence A search was conducted for randomised trials and systematic reviews of randomised trials comparing the effectiveness of monitoring with repeated biomarker measurement (BNP, NT-proBNP or troponin) or repeated cardiac imaging (echocardiography or cardiac MRI), compared to usual care without repeated measurement or imaging, that had a population or subgroup with atrial fibrillation. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 No relevant studies were identified. 8.3.4 Economic evidence Published literature No previously published economic evidence was identified for this question in the review. See also the health economic study selection flow chart in Appendix D. 8.3.5 Evidence statements Clinical No relevant clinical evidence was identified for inclusion within this review. Economic No economic evaluations were identified. 8.3.6 Recommendations and link to evidence Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection Relative values of different outcomes The critical outcomes were identified as mortality, all-cause hospitalisations and quality of life. Important outcomes were adverse events that could be related to treatment: bradycardia, hypotension, impaired renal function, hyperkalaemia, arrhythmic events. The committee sought evidence that stratified the results by age, as it was expected that older people (on average) may not respond as well to more intensive treatment regimes. Quality of the clinical evidence Natriuretic peptide monitoring General heart failure population: The review identified multiple existing meta-analyses that pooled data from a number of heterogeneous trials investigating the effect of natriuretic peptide (NP) guided therapy. The use of individual patient data (IPD) in two of the existing meta-analyses provided a higher quality source of evidence than using the data reported by each individual study, and so this review utilised data from the existing IPD meta-analyses where possible. The trials included in the existing meta-analyses differed in patient population, baseline medication, NP guided protocol and control arm protocol. The review was unable to formally assess heterogeneity of the results split by age due to reliance on aggregate data from one of the existing meta-analyses, but the low levels of heterogeneity in the overall (not age- stratified) results gave the committee some confidence that considering the trials together was a valid approach. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection An assessment of possible sources of bias showed that the randomisation and allocation concealment was either unclear or inadequate in many studies. The level of missing data was also not clear for some of the included studies, and there was limited detail in the existing meta-analyses on how the authors minimised the effects of missing data. Together these factors led to a high risk of bias assessment for many of the outcomes, including the mortality and quality of life evidence. The assessment showed generally low risk of bias in the subset of studies that contributed to the age-stratified all- cause hospitalisation data. The confidence intervals around most of the effect estimates were relatively wide, which further reduced the overall GRADE quality rating for all outcomes (with the exception of quality of life and renal function) and reduced the committee s confidence in the evidence. In particular, adverse events were not consistently reported, with many results based on only one trial, resulting in particularly large confidence intervals around the estimates of effect for those data. Heart failure and chronic kidney disease: Subgroup analyses of patients with chronic kidney disease (CKD) were available from one primary study and one of the existing meta-analyses mentioned above. These analyses provided evidence for all-cause mortality (eight studies) and all-cause hospitalisation (one study). For the all-cause hospitalisation data, the committee noted that of the 2021 patients included in the existing meta-analyses for whom an eGFR was calculated, 57% had an eGFR of 60ml/min/1.73m2 and were therefore categorised as having CKD, so the subgroup was large and robust. All of the evidence was at serious or very serious risk of bias due to insufficient information about randomisation and/or allocation concealment, and insufficient information about the planning or categorisation of the CKD subgroup analyses. All of the evidence was also imprecise, with wide confidence intervals around the effect estimates, which reduced certainty in the results. The evidence for mortality was inconsistent due to the heterogeneity between effect estimates in those with HFREF and HFpEF. The hospitalisation evidence was also rated as indirect, as the reported data were number of days in hospital rather than the preferred measure of number of hospitalisation events or hospitalised patients. Heart failure and atrial fibrillation: No studies reported on the use of NP monitoring in patients with heart failure and atrial fibrillation (AF). Monitoring using other biomarkers or repeated cardiac imaging (echocardiography or cardiac MRI) No studies comparing usual care with monitoring with troponin or combinations of different biomarkers, repeated echocardiography, or cardiac Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection MRI were identified. Trade-off between clinical benefits and harms Natriuretic peptide monitoring General heart failure population Age and comorbidities In people under 75 years of age, NP monitoring was associated with a clinically important reduction in deaths (58 fewer per thousand (from 103 fewer to 0 fewer)) and admissions (68 fewer per thousand (from 136 fewer to 4 more)) without a substantial increase in the incidence of adverse events. The committee felt that, while there was some uncertainty in this evidence, it was likely that some people under 75 years of age would benefit from NP monitoring in clinical practice. The committee agreed that the evidence supported a recommendation to consider NP monitoring in patients under 75 years of age. The evidence suggested that in people aged 75 and older, NP monitoring may result in clinically significant increase in numbers of deaths and admissions, with an average of 59 extra deaths per thousand (from 56 fewer to 200 more) and 24 extra admissions (from 47 fewer to 91 more). In terms of adverse events, there was a suggestion that people aged 75 years and older receiving NP monitoring may be more likely to develop hyperkalaemia and hypotension, although there was no clinically significant difference in the incidence of renal failure. However, the committee emphasised the very wide confidence intervals around all of these estimates of effect, which in many cases ranged from a clinically important benefit to a clinically important harm. The committee agreed that while there was no clear evidence of benefit in people aged 75 and over, there was also no clear evidence of harm. Because of the uncertainty around the impact of NP monitoring in people 75 years of age and older, the committee decided to make no recommendation for this age group. The committee discussed at length the stratification of the recommendation by age, including the biological plausibility of the finding that NP monitoring had a differential effect depending on age. The committee suggested that the metabolism of NPs may change with age, and this could make NP monitoring less useful in older patients. The committee also agreed that age could be a surrogate for comorbidity, and this could explain the benefit of a more aggressive NP monitoring strategy in younger people (i.e. with fewer comorbidities). Supporting this hypothesis, one of the existing meta-analyses conducted a post-hoc analysis suggesting that the reduced mortality associated with NP monitoring was primarily seen in patients without previous cerebrovascular accident/transient ischemic attack, diabetes or COPD, and that the benefit of NP monitoring was absent in patients with any one of those comorbidities 55 . Peripheral vascular disease was also found to be a relevant comorbidity explaining some of the association between the treatment affect and age. However, the authors of that analysis emphasise that these potential reasons for the lower effectiveness of more intensified therapy (NP monitoring) must remain speculative and should be best regarded as hypothesis generating until confirmed by further prospective Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection studies. Based on the above, the committee discussed whether the existence of comorbidities could be substituted for age in the recommendation, in terms of the population in which NP monitoring may be suitable. The committee decided against this given the speculative nature of the finding that comorbidities rather than age per se explained the differential results in different age groups, and the uncertainty about which comorbidities were most relevant. The committee agreed that as the evidence reviewed clearly showed an age- effect above and below 75 years, it was appropriate to stratify the recommendation by this factor. However, it was unanimously agreed that age should not be an absolute barrier to (or indication for) NP monitoring, and that a person s general health and the presence of comorbidities should always be considered on a case by case basis when considering NP monitoring. Role and scope of NP monitoring The committee discussed the heterogeneous nature of the NP-guided treatment protocols used in the included studies. Some studies treated to an absolute NP target; others set a personal target based on percentage drop in NP levels; and others did not aim to reduce NP levels, but used serial measurements to detect increases thought to represent deterioration and acted accordingly. The variation in the NP-guided treatment protocols made it difficult for the committee to specify a particular model of NP monitoring, but the committee agreed that the greatest benefit of NP monitoring would be as part of a treatment optimisation protocol. The reduction in deaths and hospitalisation would be most significant for people in higher risk categories, such as those who are newly diagnosed or have had a recent deterioration, and require medication titration. An NP guided treatment protocol should not, however, override clinical assessment and judgement. It was not proposed that NP levels be routinely measured in stable patients on optimised medication, as such patients would likely gain little from the intervention. Type of NP measured The committee noted that across the included studies, both BNP and NT- proBNP monitoring was utilised. The committee agreed however that NT- proBNP should be the preferred NP for monitoring for two key reasons. Firstly, one of the recommended drugs for treating heart failure interferes with BNP physiology (Sacubitril valsartan - TA388). Secondly, concerns were raised by the committee about the stability of BNP samples. BNP is stable in a blood sample for only 4-6 hours while NT-proBNP is stable for days. In order to address the stability issue, BNP can be collected in different sample tubes (EDTA or fluoride-citrate); however this often requires more blood samples to be taken and therefore makes the process more complex and open to error as well as being more resource intensive. Samples for NT- proBNP testing can be collected in standard serum tube with the rest of the Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection likely requests. Because NT-proBNP testing is likely to produce more reliable results than BNP testing, the committee agreed that where NP monitoring is conducted, NT-proBNP should be the peptide measured. Impact of ejection fraction The committee then discussed whether the recommendation should be limited to people with heart failure with reduced (HFREF), rather than preserved (HFpEF), ejection fraction. Although the results of the review were not formally split into HFREF and HFpEF, the committee acknowledged that a substantial majority of the patients in the included studies had HFREF. Because the committee agreed that NP monitoring would have greatest benefit as part of a treatment optimisation protocol, and there was no evidence for long term prognostic benefit from pharmaceutical treatment in HFPEF, it was unlikely that patients with HFPEF would receive significant benefit from NP monitoring. This aligned with subgroup analyses reported in the existing meta-analyses, 279 55 which showed that the mortality and all- cause hospitalisation benefit of NP monitoring was found in HFREF but not HFPEF patients. For these reasons, the committee decided that the recommendation should be limited to people with HFREF. People with heart failure and chronic kidney disease The committee considered the evidence regarding the use of NP-guided treatment strategies in patients with HF and CKD and agreed that although there was suggestion of a clinically important increase in deaths (9 more (from 105 fewer to 172 more)) these results were imprecise making it difficult for the committee to have confidence in the results. In addition to this there was inconsistency in the results reported for people with HFREF and HFpEF which further reduced the committees confidence in the results. Regardless of this the committee agreed that the evidence may be suggestive of a clinically significant increase in deaths with NP monitoring and therefore people with HF and CKD should be monitored by a specialist. The committee noted the findings of the separate review of pharmaceutical treatment for HF in people with both HF and CKD, which generally concluded that most patients with CKD should be offered the same treatment options as patients without CKD. The committee noted that while the patients with CKD in the original trials made up more than half the total number of participants, many of the included studies excluded patients with severe renal disease with the majority of patients included in the trials having an eGFR of . Therefore, the results cannot be extrapolated to patients with more severe CKD. People with heart failure and atrial fibrillation The committee discussed NP monitoring in patients with HF and AF. In the absence of evidence in this subgroup, and given the effect of AF itself on NP levels the committee agreed that no recommendation could be made on this topic. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection Monitoring using other biomarkers or repeated cardiac imaging (echocardiography or cardiac MRI) Given the absence of evidence on the clinical effectiveness of monitoring using other troponin, combinations of biomarkers, or repeated cardiac imaging, the committee agreed to make no recommendation in these areas. The committee acknowledged its related research recommendation on the added value of cardiac MRI in the diagnosis of heart failure and its aetiology, and considered that further research in that area would be necessary before developing an evidence base for the use of cardiac imaging as a monitoring tool. Trade-off between net clinical effects and costs Three economic evaluations (two from a UK perspective and one from an Austrian perspective) were identified and included in this review comparing NP monitoring to usual care. The Austrian cost-utility analysis assessed patients with heart failure who had recently been discharged after a heart failure hospitalisation. The study compared usual care by a primary care physician as well as usual care by a nurse-led multidisciplinary team (MDT) to intensive NP monitoring. Mortality and hospitalisation rates were taken from Berger et al. 2010 identified in the clinical review. 34 This economic evaluation suggests that NP monitoring is more effective and less costly and therefore dominates both usual care in the community and the nurse-led MDT. The committee did not put much weight on the results of this study as the relative effect of NP monitoring was taken from only one of 13 studies included in the clinical review and therefore is unlikely to reflect the best estimate of the effect of NP monitoring, and was also not from a UK perspective. This study was assessed as being partially applicable with potentially serious limitations. One UK cost-utility analysis compared usual care in the community and/or usual care through specialist clinical assessment to natriuretic peptide monitoring. The model assessed two population groups: patients with chronic heart failure due to LVSD, and patients with heart failure from any cause, and also presented results stratified by age. This study found that NP monitoring is cost effective for patients with chronic heart failure and LVSD at any age compared to specialist management [ICER: 3,304 per QALY gained]. The probability that NP monitoring is cost effective at the 20,000 threshold was 99%. Similar results were found for patients with CHF and LVSD <75 years old [ICER: 2,871 per QALY gained] with a 98% probability of being cost effective at the 20,000 threshold. NP monitoring was also found to be cost effective in patients with CHF and LVSD 75 years old [ICER: 5,392 per QALY gained], however this is uncertain as there is only a 68% probability that NP monitoring is cost effective at the 20,000 threshold. The committee noted that a larger proportion of the population were less than 75 years old in these trials, so the result for any age could be driven by this group. This study also found that NP monitoring is cost effective compared to both usual care in the community and usual care by a specialist for patients with CHF of any cause at any age [ICER: 14,694 per QALY gained comparing Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection NP monitoring to specialist management]. The probability that NP monitoring is cost effective at the 20,000 threshold is 84%. NP monitoring is also found to be cost effective for the two age sub-groups (75 and under, and greater than 75), but again reflected the results found for those with CHF and LVSD, with greater uncertainty in the result for those older than 75 (50% probability cost effective at 20,000 threshold) than those under 75 (98% probability cost effective at 20,000 threshold). The committee noted that the majority of patients in the trials used for the analysis had HF-REF. The committee noted that this analysis only included 4 of 13 studies included in the clinical review and therefore may not reflect the most recent clinical evidence. This study was assessed as directly applicable with minor limitations. One UK cost-utility analysis compared specialist-led clinically guided therapy to specialist led NP-guided therapy in patients with heart failure who had recently been discharged from hospital following an acute episode. All heart failure patients and HF-REF patients were sub-grouped by age (less than 75 years old, 75 and older) whereas only HF-PEF patients less than 75 years of age were assessed. IPD data was used to estimate the relative effect of NP guided care on all-cause mortality and all-cause hospitalisations reported by Brunner le Rocca et al. 2006.55 The study found NP monitoring to be cost effective for all sub-groups, and even dominated specialist-led clinically- guided therapy in all heart failure patients over 75. The study also reported incremental net monetary benefit results with 95% confidence intervals. These results suggest there is uncertainty in the cost effectiveness of NP monitoring for HF-PEF patients less than 75 years of age and both all heart failure and HF-REF patients over 75 years of age, with 95% confidence intervals ranging from negative to positive. The study also carried out a sensitivity analysis using IPD meta-analysis data from a more recent health technology assessment, in which this economic evaluation was developed. However, this was only assessed for HF-REF patients less than 75 years old. The results of this suggest that NP monitoring is cost effective compared to clinically-guided therapy, however this is more uncertain than the base-case results as the 95% confidence intervals of the incremental net monetary benefit now range from negative to positive. The committee discussed that the base-case results in this study may not reflect the best estimate of the relative effect of NP monitoring and suggested that the recent IPD meta-analysis data was more reflective of the clinical evidence presented in the review for this guideline. This study was assessed as being directly applicable with minor limitations. As previously mentioned, the committee agreed not to recommend NP monitoring for HFPEF patients due to the lack effective pharmacological treatments available for these patients and most of the studies did not include this population. The committee also considered that the clinical and cost effectiveness evidence for NP monitoring in heart failure patients over 75 years of age was too uncertain to make a recommendation for these patients. However, the committee considered that NP monitoring is likely to be cost Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Recommendations Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection effective for HFREF patients under the age of 75. The committee noted the variety of monitoring protocols used in the RCTs, and raised some concern about the potential range in cost of the intervention depending on the frequency of monitoring. The most recent cost-effectiveness analysis assumed NP testing every 3 months, but that this would cease after 18 months. The committee considered that this was a reasonable average, but also recognised that due to the low ICERs that even if the average frequency of monitoring were to be slightly higher that it would still be cost effective. Due to the uncertainty of the cost effectiveness of NP monitoring when the IPD data is used and the potential variation in cost of NP monitoring the committee decided to make a consider recommendation for people under the age of 75 with HF-REF . No economic evaluations were identified for those with heart failure and CKD or AF. As mentioned in the Trade-off between clinical benefits and harms section above the committee did not consider that those with heart failure with CKD should not be monitored using NP due to concern of increased risk of death, but instead be monitored by a specialist. There was no clinical evidence identified for the heart failure plus atrial fibrillation population and therefore the committee could not assess the cost effectiveness of NP monitoring in this population and no recommendation was made for this group. Other considerations A single study was included in the 2010 update (CG108) of this question30 . The committee agreed that this study should now be excluded as it no longer met the review protocol. This was due to the decision to impose a study duration threshold of a minimum of 6 months. The committee agreed that due to the chronic nature of the condition, this length of follow-up was necessary in order to be able to make appropriate recommendations. The committee discussed current practice regarding BNP measurement. It was agreed that usual practice is to measure BNP at the point of diagnosis. Repeated measurement is usually done only for specific populations (for example, people awaiting transplant), and by some specialist centres. It was felt that this recommendation, although not substantially different from the previous recommendation, may increase the uptake of NP monitoring in younger, newly diagnosed HFREF patients. Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 8.4 Telemonitoring and self-monitoring Telemonitoring and self monitoring in people with heart failure has been a area of interest not only amongst clinicians in primary and community care, but also with commissioners of services. The main drive for its use has been the perception that these interventions could reduce the need for face-to- face contact with patients, and promote self care. The 2010 guidelines did not make any recommendations for its implementation due to the difficulty in interpreting whether the differences shown in the outcomes were due to the monitoring intervention or the additional access provided to specialist care. Current use of these methods of monitoring patients remains patchy throughout the country Telemonitoring techonology has developed since publication of the last guideline, and the publication of further reviews and studies prompted the question of the clinical and cost effectiveness of telemonitoring to be revisited. 8.4.2 Review question: What is the clinical and cost effectiveness of telemonitoring and self- monitoring compared with usual care, in people with heart failure? For full details see review protocol in appendix A. Table 89: PICO characteristics of review question Population People with heart failure in a community or outpatient setting. The results will be presented separately in each of the following strata: recently discharged patients patients recruited in the community Interventions Structured telephone support monitoring or self-care management or both delivered using simple telephone technology Telemonitoring digital/broadband/satellite/wireless or Bluetooth transmission of physiological or other non-invasive data Interventions needed to be scheduled, as opposed to offering telephone follow-up on an 'as needed' basis. Intervention must have been initiated by a healthcare professional (medical, nursing, social work, pharmacist) and delivered to people with heart failure living in the community as the only aftercare intervention, without protocol-driven home visits or intensified clinic follow-up. The intervention has to be targeted at the person and intended to address their concerns and problems, not those of caregivers. The participant must not have been visited at home by a specialised heart failure healthcare professional or study personnel for the purpose of education or clinical assessment other than as an initiation visit to set up equipment. The results for telemonitoring and structured telephone support will be presented separately. Comparators Usual care 'Usual care' consists of standard post-discharge care without intensified attendance at cardiology clinics or clinic-based heart failure disease management programme, or home visiting as described above. Studies will be excluded if there was any previous exposure to telemonitoring or structured telephone support for the usual care or intervention arms prior to the start of the study. Outcomes CRITICAL All-cause mortality during study (dichotomous) Quality of life during study (continuous) All-cause hospitalisations during study (dichotomous) Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 IMPORTANT Adherence to intervention Study design Systematic reviews of RCTs RCTs 8.4.3 Clinical evidence This review was conducted as an update to an existing Cochrane review which included randomised trials comparing the effectiveness of telemonitoring and structured telephone support versus usual these are summarised in Table 90 and Table 91 below. A search was conducted from the publication date onwards in order to update the review, which led to a further five studies being identified for inclusion. These studies 7, 81, 247, 291, 320 are summarised in Table 92 below. Evidence from these studies is summarised in the clinical evidence summaries below (Table 93, Table 94 and Table 95). See also the study selection flow chart in Appendix C, forest plots in Appendix E, study evidence tables in Appendix F, GRADE tables in Appendix H and excluded studies list in Appendix I. A HTA report252 published in 2013, which reviewed the effectiveness of structured telephone support and telemonitoring in people recently admitted for an exacerbation of heart failure, was also identified. The Cochrane review was prioritised for update over this review as it included a broader population, was more recently published and included RCT level data only. were subsequently excluded by the Cochrane review as the intervention arms included home visits or were targeted at the caregiver as well as the person with heart failure. In addition to this two RCTs included in the Cochrane review 48, 376 on structured telephone support did not have any extractable data and were therefore excluded in this review. The studies included within the Cochrane review were incorporated into our guideline in the following ways: Data has been analysed separately for patients who have recently been admitted to hospital and for patients recruited within the community. Where the study has not reported this information, we have included a mixed strata as these papers potentially represent a combination of recently admitted and community dwelling people. The outcomes quality of life and adherence to intervention were reported narratively by the Cochrane review. For the current review, quality of life and adherence data have only been included when reported by the study in an extractable format. Risk of bias assessment per study was directly adopted for the outcomes all-cause mortality and all-cause hospitalisation. The outcome quality of life was downgraded where studies reported final values with no baseline scores or where the intervention and comparison scores were not matched at baseline. Two of the included studies reported multiple intervention arm66, 228 Data from these studies was separated out into the two interventions of interest (structured telephone support and telemonitoring). Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Funnel plots were constructed by the Cochrane authors to assess for potential publication bias (appendix F) for the outcomes all-cause mortality and all-cause hospitalisation. This was taken into consideration when assessing the quality of the evidence for strata containing more than 5 studies. Table 90: Summary of studies included in the Cochrane review153 Structured telephone support Study Intervention and comparison Population Outcomes Comments Angermann Intervention: Structured telephone support Comparator: Usual care People with HF 18 years of age, hospitalised with signs and symptoms of decompensated HF Mean age: 68.6 years M/F (%): 71/29 Germany All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Intervention: Structured telephone support Comparator: Usual care People with HF from general and internal medicine and cardiology clinics Mean age: 60.7 years M/F (%): 52/58 USA All-cause mortality Quality of life Strata: recent admission Quality of life downgraded for risk of bias as all scores were not matched at baseline and final values were reported. Intervention: Structured telephone support Comparator: Usual care People discharged from acute care to home with a primary diagnosis of HF Mean age: 75 years M/F (%): 47/53 USA All-cause mortality Strata: recent admission Bento Intervention: Structured telephone support People with a All-cause mortality All-cause Strata: community Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Comparator: Usual care diagnosis of HF and NYHA class I-IV, treated at a HF outpatient clinic with telephone access Mean age: years Control: 61 years M/F (%): 70/30 Brazil hospitalisation Capomolla Intervention: Structured telephone support Comparator: Usual care People discharged from specialist HF units to home Mean age: 57 years M/F (%): 88/12 Italy All-cause mortality Strata: recent admission Chaudhry Structured telephone support Comparator: Usual care People who had recently been hospitalised for HF Median age: 61 years M/F (%): 58/42 USA All-cause mortality All-cause hospitalisation Strata: recent admission (TENS- Structured telephone support Telemonitoring Comparator: Usual care People with a recent admission for HF and Mean age: 67 years M/F (%): 77/23 All-cause mortality All-cause hospitalisation Strata: recent admission Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Germany, Netherlands, UK DeBusk Intervention: Structured telephone support Comparator: Usual care People hospitalised with a provisional diagnosis of HF from Kaiser Permanente Mean age: 72 years M/F (%): 51/49 USA All-cause mortality All-cause hospitalisation Strata: recent admission DeWalt Intervention: Structured telephone support Comparator: Usual care People with confirmed HF Mean age: 62.5 years M/F (%): 47/53 USA All-cause mortality Quality of life Strata: community Domingues Intervention: Structured telephone support Comparator: Usual care People with HF, with a LVEF 45% Mean age: 63 years M/F (%): 68/32 Brazil All-cause mortality All-cause hospitalisation Strata: recent admission Galbreath Intervention: Structured telephone support Comparator: Usual care People with symptoms of HF and documented systolic or diastolic dysfunction Mean age: 71 years All-cause mortality Strata: community Intervention: Structured telephone n=181 All-cause mortality Strata: community Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments support Comparator: Usual care People with HF being evaluated in cardiology clinic Mean age: 67 years USA All-cause hospitalisation Intervention: Structured telephone support Comparator: Usual care Outpatients with stable HF Mean age: 65 years Argentina All-cause mortality All-cause hospitalisation Quality of life Strata: community Intervention: Structured telephone support Comparator: Usual care People with a recent hospital discharge due to a primary diagnosis of HF Mean age: 73 years Australia All-cause mortality All-cause hospitalisation Strata: community Laramee Intervention: Structured telephone support Comparator: Usual care People admitted to hospital with primary or secondary diagnosis of HF Mean age: 71 years USA All-cause mortality All-cause hospitalisation Adherence to intervention Strata: recent admission Adherence to intervention downgraded for risk of bias as the scale used was not validated. Mortara Structured telephone support People with HF NYHA class II-IV and All-cause mortality All-cause hospitalisation Strata: mixed Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Telemonitoring Comparator: Usual care Mean age: 60 years UK, Poland, Italy Rainville Intervention: Structured telephone support Comparator: Usual care People aged 50 years discharged from hospital with HF Mean age: 70 years USA All-cause mortality Strata: recent admission Ramachandr Intervention: Structured telephone support Comparator: Usual care People attending a HF clinic with symptoms of HF and LVEF <40% Mean age: 44.5 years India Quality of life Strata: mixed Riegel Intervention: Structured telephone support Comparator: Usual care People discharged from hospital with HF Mean age: 74 years USA All-cause mortality All-cause hospitalisation Strata: recent admission Riegel Intervention: Structured telephone support Comparator: Usual care Hispanic people hospitalised for HF Mean age: 72 years All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments USA Intervention: Structured telephone support Comparator: Usual care non-Hispanic and Hispanic people with documented systolic dysfunction Mean age: 59 years USA All-cause mortality All-cause hospitalisation Quality of life Strata: community Tsuyuki Intervention: Structured telephone support Comparator: Usual care People discharged from hospital with HF Mean age: 72 years Canada All-cause mortality Strata: recent admission Wakefield Intervention: Structured telephone support Comparator: Usual care People hospitalised for HF exacerbation Mean age: 69 years USA All-cause mortality All-cause hospitalisation Strata: recent admission Table 91: Summary of studies included in the Cochrane review153 - Telemonitoring Study Intervention and comparison Population Outcomes Comments Antonicelli Intervention: Telemonitoring Comparator: Usual Care People hospitalised for worsening symptoms and All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Quality of life downgraded for risk of bias as all scores were not matched at Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments signs of HF Mean age: 78 years M/F (%): 78/22 Italy baseline and final values were reported. Intervention: Telemonitoring Comparator: Usual care People with HF and NYHA class I-IV Mean age: 66 years M/F (%): 70/30 The Netherlands All-cause mortality Strata: mixed Biannic Intervention: Telemonitoring Comparator: Usual care Elderly people with severe HF recently hospitalised for HF Mean age: M/F (%): France All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Intervention: Telemonitoring Comparator: Usual care People with HF who have been admitted to hospital within the past year Mean age: 72 years M/F (%): 71/29 USA All-cause mortality All-cause hospitalisation Quality of life Strata: mixed Quality of life downgraded for risk of bias as all scores were not matched at baseline and final values were reported. (TENS- Structured telephone support People with a All-cause mortality All-cause Strata: recent admission Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Telemonitoring Comparator: Usual care recent admission for HF and Mean age: 67 years M/F (%): 77/23 Germany, Netherlands, UK hospitalisation De Lusignan Intervention: Telemonitoring Comparator: Usual care People with HF confirmed by a cardiologist, identified from the database of an academic general practice Mean age: 75 years Gender not reported UK All-cause mortality Strata: mixed Dendale Intervention: Telemonitoring Comparator: Usual care People hospitalised with HF Mean age: 76 years M/F (%): 65/35 Belgium All-cause mortality All-cause hospitalisation Strata: recent admission Giordano Intervention: Telemonitoring Comparator: Usual care People with confirmed HF with LVEF<40% and at hospitalisation for acute HF in the prior year Mean age: 57 years All-cause mortality All-cause hospitalisation Unable to obtain full text paper. Included in mixed strata Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Italy Goldberg Intervention: Telemonitoring Comparator: Usual care People hospitalised with NYHA class III- IV, with a LVEF < Mean age: 59 years USA All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Koehler Intervention: Telemonitoring Comparator: Usual care People with HF in NYHA class II or III with an LVEF of Mean age: 66.9 years Germany All-cause mortality All-cause hospitalisation Quality of life Strata: mixed Quality of life downgraded for risk of bias as final scores were reported by the study with no report of baseline scores. Intervention: Telemonitoring Comparator: Usual care People who were hospitalised for HF with NYHA class III- IV Mean age: 73.9 years Sweden All-cause mortality All-cause hospitalisation Strata: recent admission Mortara Structured telephone support Telemonitoring Comparator: Usual care People with HF NYHA class II-IV and Mean age: 60 years All-cause mortality All-cause hospitalisation Strata: mixed Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments UK, Poland, Italy Intervention: Telemonitoring Comparator: Usual care People with HF hospitalised for >24 hours within 4 weeks prior to the study Median age (IQR): M/F(%): Austria All-cause mortality All-cause hospitalisation Strata: recent admission Intervention: Telemonitoring Comparator: Usual care Ambulatory people diagnosed with HF Mean age: 55.1 years Canada All-cause mortality All-cause hospitalisation Quality of life Strata: mixed Soran Intervention: Telemonitoring Comparator: Usual care People with a diagnosis of HF secondary to systolic dysfunction Mean age: 76 years USA All-cause mortality All-cause hospitalisation Strata: Mixed Intervention: Telemonitoring Comparator: Usual care People with HF hospitalisations in the last 6 months and at high risk of All-cause mortality Strata: recent admission Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments early re- hospitalisation Mean age: 72 years Italy Vuorinen Intervention: Telemonitoring Comparator: Usual care People with systolic HF Mean age: 58 years Finland All-cause mortality Strata: mixed Woodend Intervention: Telemonitoring Comparator: Usual care People with symptomatic HF (NYHA Class II or greater) Mean age: 68 years Canada All-cause mortality All-cause hospitalisation Strata: recent admission Table 92: Summary of studies included in the update of the Cochrane review Study Intervention and comparison Population Outcomes Comments Al-Sutari Intervention: Structured telephone support Comparator: Usual care People with heart and NYHA class II or III) who attended the cardiac clinic of an educational hospital Mean age: 64.78 All-cause mortality All-cause hospitalisation Strata: community Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Jordan Intervention: Structured telephone support Comparator: Usual care People living in the community with a diagnosis of HF Mean age: 55.3 USA Quality of life Strata: community Intervention: Structured telephone support + telemonitoring Comparator: Usual care People admitted to hospital as inpatients or on observation being treated for decompensated HF Median age (IQR): M/F(%): USA All-cause mortality All-cause hospitalisation Quality of life Strata: recent admission Quality of life downgraded for risk of bias as final scores were reported by the study with no report of baseline scores. Intervention: Structured telephone support Comparator: Usual care People with clinical signs and symptoms of HF Mean age: 72.6 USA All-cause mortality All-cause hospitalisation Strata: recent admission Stavrianopo Intervention: Structured telephone support Comparator: Usual care People with HF Quality of life Strata: mixed Chronic Heart Failure Monitoring NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Study Intervention and comparison Population Outcomes Comments Greece Monitoring Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Table 93: Clinical evidence summary: Structured telephone support versus usual care Outcomes No of Participants (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with Usual care Risk difference with structured telephone support (95% CI) Recent admission All-cause mortality 5359 months due to risk of bias, imprecision, publication bias (from 2 fewer to 32 fewer) All-cause hospitalisation 4549 months due to risk of bias, publication bias (from 26 fewer to 30 more) Quality of life (SF-36 Physical health component) Better indicated by higher due to risk of bias The mean QoL in the control groups was The mean QoL in the intervention groups was Quality of life (SF-36 Physical functioning component) Better indicated by higher due to risk of bias The mean QoL in the control groups was The mean QoL in the intervention groups was Quality of life (MLWHFQ) Better indicated by lower imprecision The mean QoL in the control groups was The mean QoL in the intervention groups was (6.48 lower to 4.88 higher) Monitoring Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Outcomes No of Participants (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with Usual care Risk difference with structured telephone support (95% CI) Quality of life (EQ-5D) Better indicated by higher due to imprecision The mean QoL in the control group was The mean QoL in the intervention group was (0.03 lower to 0.11 higher) Quality of life (HFSS) Better indicated by higher due to risk of bias The mean QoL in the control groups was The mean QoL in the intervention groups was (2.4 lower to 4.8 higher) Adherence to intervention (weight self daily) Better indicated by higher due to risk of bias, imprecision The mean adherence to intervention in the control groups was The mean adherence to intervention in the intervention groups was Adherence to intervention (check ankles and feet for swelling) Better indicated by higher due to risk of bias, imprecision The mean adherence to intervention in the control groups was The mean adherence to intervention in the intervention groups was Adherence to intervention (follow fluid recommendations) Better indicated by higher due to risk of bias, imprecision The mean adherence to intervention in the control groups was The mean adherence to intervention in the intervention groups was Adherence to intervention (follow low-salt diet) due to risk of bias, The mean adherence to intervention in the control groups was The mean adherence to intervention in the intervention groups was Monitoring Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Outcomes No of Participants (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with Usual care Risk difference with structured telephone support (95% CI) Better indicated by higher Adherence to intervention (take medication) Better indicated by higher due to risk of bias The mean adherence to intervention in the control groups was The mean adherence to intervention in the intervention groups was (0.04 lower to 0.24 higher) Community All-cause mortality 4495 months due to imprecision, publication bias (from 28 fewer to 5 more) All-cause hospitalisation 2694 months due to imprecision, publication bias (from 44 fewer to 107 fewer) Quality of life (MLWHFQ) Better indicated by lower months HIGH The mean QoL in the intervention groups was Quality of life (HDS) Better indicated by lower due to risk of bias, imprecision The mean QoL in the control groups was The mean QoL in the intervention groups was Mixed Monitoring Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Outcomes No of Participants (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with Usual care Risk difference with structured telephone support (95% CI) months due to risk of bias, imprecision (from 28 fewer to 137 more) All-cause hospitalisation 254 months due to risk of bias, imprecision (from 48 fewer to 216 more) Quality of life (MLWHFQ) Better indicated by lower due to risk of bias, imprecision The mean QoL in the control groups was The mean QoL in the intervention groups was Quality of life (KCCQ HRQoL) Better indicated by higher due to risk of bias, imprecision The mean QoL in the control groups was The mean QoL in the intervention groups was 1 Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias 2 Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs 3 Funnel plots constructed by the Cochrane authors showed asymmetry and the potential of a strong publication bias in the studies included within the review 4 Unable to calculate as studies reported MD and were analysed using the generic inverse variance method Table 94: Clinical evidence summary: Telemonitoring versus usual care Outcomes No of Quality of the evidence Relative Anticipated absolute effects Monitoring Chronic Heart Failure NICE 2018. 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ISBN: Participants (studies) Follow up (GRADE) effect Risk with Usual care Risk difference with telemonitoring (95% CI) Recent admission All-cause mortality 1480 months due to risk of bias, publication bias (from 38 fewer to 85 fewer) All-cause hospitalisation 1400 months due to risk of bias, imprecision, publication bias, inconsistency (from 12 fewer to 208 fewer) Quality of life (SF-12 Physical) Better indicated by higher HIGH The mean QoL in the control groups was The mean QoL in the intervention groups was (0.15 lower to 4.95 higher) Quality of life (SF-12 Mental) Better indicated by higher HIGH The mean QoL in the control groups was The mean QoL in the intervention groups was (2.1 lower to 3.5 higher) Quality of life (HDS) Better indicated by lower HIGH The mean QoL in the control groups was The mean QoL in the intervention groups was (2.7 lower to 1.3 higher) Quality of life (MLWHFQ) Better indicated by lower due to risk of bias The mean QoL in the intervention groups was Monitoring Chronic Heart Failure NICE 2018. 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