Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure

OBJECTIVE: Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. METHODS: We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. RESULTS: In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (−£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (−£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. CONCLUSIONS: We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care

The healthcare costs of heart failure during the last five years of life: : A retrospective cohort study

Background Evidence on the economic impact of heart failure (HF) is vital in order to predict the cost-effectiveness of novel interventions. We estimate the health system costs of HF during the last five years of life. Methods We used linked primary care and mortality data accessed through the Clinical Practice Research Datalink (CPRD) to identify 1555 adults in England who died with HF in 2012/13. We used CPRD and linked Hospital Episode Statistics to estimate the cost of medications, primary and hospital healthcare. Using GLS regression we estimated the relationship between costs, HF diagnosis, proximity to death and patient characteristics. Results In the last 3 months of life, healthcare costs were £8827 (95% CI £8357 to £9296) per patient, more than 90% of which were for inpatient or critical care. In the last 3 months, patients spent on average 17.8 (95% CI 16.8 to 18.8) days in hospital and had 8.8 (95% CI 8.4 to 9.1) primary care consultations. Most (931/1555; 59.9%) patients were in hospital on the day of death. Mean quarterly healthcare costs in quarters after HF diagnosis were higher (£1439; [95% CI £1260 to £1619]) than in quarters preceding diagnosis. Older patients and patients with lower comorbidity scores had lower costs. Conclusions Healthcare costs increase sharply at the end of life and are dominated by hospital care. There is potential to save money by implementation and evaluation of interventions that are known to reduce hospitalisations for HF, particularly at the end of life

B-type natriuretic peptide-guided therapy for heart failure (HF):a systematic review and meta-analysis of individual participant data (IPD) and aggregate data

Abstract Background We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). Methods Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. Results We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53–0.92, patients < 75 years old and HR 1.07, 95% CI 0.84–1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71–0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83–2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). Conclusion BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear. Systematic review registration PROSPERO CRD4201300533

Outcome Monitoring After Cardiac Surgery (OMACS): a single-centre prospective cohort study of cardiac surgery patients

Introduction More than 30 000 cardiac surgery procedures are performed in the UK each year, however, postoperative complications and long-term failure of interventions are common, leading to repeated surgeries. This represents a significant burden on the patient and health service.Routinely, patients are discharged to their general practitioner 6 weeks postoperatively and research studies typically only report short-term outcomes up to 1 year after surgery, together this makes long-term outcomes of cardiac surgery difficult to monitor. Further, traditional research methods have yet to advance understanding of what causes early complications and why surgical interventions fail.Methods and analysis This prospective cohort study will characterise participants undergoing cardiac surgery at baseline, describe short-term, medium-term and long-term health outcomes postoperatively and collect tissue samples.All eligible adult patients undergoing cardiac surgery at the Bristol Heart Institute, UK will be approached for consent. Recruitment is expected to continue for up to 10 years resulting in the largest cohort of cardiac patients reported to date. Blood, urine and waste tissue samples will be collected during admission. Samples, along with anonymised data, will be used to investigate outcomes and inform predictive models of complications associated with cardiac surgery.Data about the surgical admission will be obtained from hospital databases and medical notes. Participants may be monitored up to 5 years postoperatively using data obtained from NHS digital. Participants will complete health questionnaires 3 months and 12 months postoperatively.The analysis of data and tissue samples to address specific research questions will require separate research protocols and ethical approval.Ethics and dissemination This study was approved by the East Midlands Nottingham 2 Research Ethics Committee.Findings will be disseminated through peer-reviewed publications and presentation at national and international meetings. Participants will be informed of results in annual newsletters.Trial registration number ISRCTN90204321

Adherence to transfusion strategies in a randomized controlled trial: experiences from the TITRe2 trial

Adherence to transfusion strategies in a randomized controlled trial: experiences from the TITRe2 tria

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure

Objective Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction.Methods We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients &lt;75 years; (2) HFpEF patients &lt;75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results.Results In younger patients (&lt;75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (−£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (−£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect.Conclusions We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care

Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia

Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimens on immunity, and thus infectious susceptibility and response to immunisation. Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimen<br/