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

Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): A randomised controlled trial

© 2015 Appelboam et al. Open Access article distributed under the terms of CC BY-ND-NC. Background The Valsalva manoeuvre is an internationally recommended treatment for supraventricular tachycardia, but cardioversion is rare in practice (5-20%), necessitating the use of other treatments including adenosine, which patients often find unpleasant. We assessed whether a postural modification to the Valsalva manoeuvre could improve its effectiveness. Methods We did a randomised controlled, parallel-group trial at emergency departments in England. We randomly allocated adults presenting with supraventricular tachycardia (excluding atrial fibrillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre (done semi-recumbent with supine repositioning and passive leg raise immediately after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40 mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation, stratified by centre, was done centrally and independently, with allocation with serially numbered, opaque, sealed, tamper-evident envelopes. Patients and treating clinicians were not masked to allocation. The primary outcome was return to sinus rhythm at 1 min after intervention, determined by the treating clinician and electrocardiogram and confirmed by an investigator masked to treatment allocation. This study is registered with Current Controlled Trials (ISRCTN67937027). Findings We enrolled 433 participants between Jan 11, 2013, and Dec 29, 2014. Excluding second attendance by five participants, 214 participants in each group were included in the intention-to-treat analysis. 37 (17%) of 214 participants assigned to standard Valsalva manoeuvre achieved sinus rhythm compared with 93 (43%) of 214 in the modified Valsalva manoeuvre group (adjusted odds ratio 3·7 (95% CI 2·3-5·8;

Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study

Objective To quantify the change in prescribing of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis, and any concurrent change in the incidence of infective endocarditis, following introduction of a clinical guideline from the National Institute for Health and Clinical Excellence (NICE) in March 2008 recommending the cessation of antibiotic prophylaxis in the United Kingdom

Central and peripheral quadriceps fatigue in congestive heart failure

AbstractAimsThe clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors.Methods and resultsWe studied 10 men with CHF and 10 healthy age-matched controls. Compared with a rest condition, 10min after incremental maximal cycle exercise, twitch quadriceps force in response to supramaximal magnetic femoral nerve stimulation fell in both groups (CHF 14.1%±18.1%, p=0.037; Control: 20.8±11.0%, p<0.001; no significant difference between groups). There was no significant change in quadriceps maximum voluntary contraction voluntary force. The difference in the motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex between rest and exercise conditions at 10min, normalised to the peripheral action potential, also fell significantly in both groups (CHF: 27.3±38.7%, p=0.037; Control: 41.1±47.7%, p=0.024). However, the fall in MEP was sustained for a longer period in controls than in patients (p=0.048).ConclusionsThe quadriceps is more susceptible to fatigue, with a similar fall in TwQ occurring in CHF patients at lower levels of exercise. This is associated with no change in voluntary activation but a lesser degree of depression of quadriceps motor evoked potential

Multicenter Randomized Controlled Crossover Trial Comparing Hemodynamic Optimization Against Echocardiographic Optimization of AV and VV Delay of Cardiac Resynchronization Therapy:The BRAVO Trial

Objectives: BRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method. Background: Cardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform. Methods: This study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro–B-type natriuretic peptide. Results: A total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro–B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms. Conclusions: Optimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829

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

Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction : a systematic review and economic evaluation

BACKGROUND: Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction. METHODS: A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate. RESULTS: A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectiveness analysis produced incremental costs of £4878, incremental quality-adjusted life-years of 1.34 and an incremental cost-effectiveness ratio of £3650. Probabilistic sensitivity analyses showed that at thresholds of £20,000 and £30,000 per quality-adjusted life-year coenzyme Q10 had a high probability (95.2% and 95.8%, respectively) of being more cost-effective than standard care alone. Scenario analyses in which the population and other model assumptions were varied all found coenzyme Q10 to be cost-effective. The expected value of perfect information suggested that a new trial could be valuable. LIMITATIONS: For most outcomes, data were available from few trials and different trials contributed to different outcomes. There were concerns about risk of bias and whether or not the results from included trials were applicable to a typical UK population. A lack of individual participant data meant that planned detailed analyses of effect modifiers were not possible. CONCLUSIONS: Available evidence suggested that, if prescribed, coenzyme Q10 has the potential to be clinically effective and cost-effective for heart failure with a reduced ejection fraction. However, given important concerns about risk of bias, plausibility of effect sizes and applicability of the evidence base, establishing whether or not coenzyme Q10 is genuinely effective in a typical UK population is important, particularly as coenzyme Q10 has not been subject to the scrutiny of drug-licensing processes. Stronger evidence is needed before considering its prescription in the NHS. FUTURE WORK: A new independent, well-designed clinical trial of coenzyme Q10 in a typical UK heart failure with a reduced ejection fraction population may be warranted. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018106189. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 4. See the NIHR Journals Library website for further project information

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