B-type natriuretic peptide-guided treatment for heart failure.

BACKGROUND: Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. OBJECTIVES: To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. SEARCH METHODS: Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. SELECTION CRITERIA: We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a clinical outcome were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. MAIN RESULTS: We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP-guided treatment with clinical assessment alone. The evidence for all-cause mortality using NP-guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence).The evidence suggested heart failure admission was reduced by NP-guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all-cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence).Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP-guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD -0.03, 95% CI -1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence).We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. AUTHORS' CONCLUSIONS: In patients with heart failure low-quality evidence showed a reduction in heart failure admission with NP-guided treatment while low-quality evidence showed uncertainty in the effect of NP-guided treatment for all-cause mortality, heart failure mortality, and all-cause admission. Uncertainty in the effect was further shown by very low-quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.

BACKGROUND: Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS: We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS: Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION: Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING: UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

Optimal loading dose for the initiation of warfarin: a systematic review.

BACKGROUND: Selection of the right warfarin dose at the outset of treatment is not straightforward, and current evidence is lacking to determine the optimal strategy for initiation of therapy. METHODS: We included randomized controlled trials in patients commencing anticoagulation with warfarin, comparing different loading dose or different regimens.We searched Medline, EMBASE, the Cochrane Library and the NHS Health Economics Database up to June 2009. Primary outcomes were time to stable INR and adverse events. We summarised results as proportion of INRs in range from date of initiation and compared dichotomous outcomes using relative risks (RR) and calculated 95% confidence intervals (CIs). RESULTS: We included 11 studies of 1,340 patients newly initiated on warfarin. In two studies that used single INR measures, a loading dose of 10 mg compared to 5 mg led to more patients in range on day five. However, in two studies which measured two consecutive INRs, a loading dose of 10 mg compared to 5 mg did not lead to more patients in range on day five (RR = 0.86, 95% CI, 0.62 to 1.19, p = 0.37). Patients receiving a 2.5 mg initiation does took longer to achieve the therapeutic range, whilst those receiving a calculated initiation dose achieved target range 0.8 days quicker (4.2 days vs. 5 days, p = 0.007). More elderly patients receiving an age adjusted dose achieved a stable INR compared to the Fennerty protocol (48% vs. 22% p = 0.02) and significantly fewer patients on the age adjusted regimens had high out-of-range INRs. Two studies report no significant differences between genotype guided and 5 mg or 10 mg initiation doses and in the one significant genotype study the control group INRs were significantly lower than expected. CONCLUSION: Our review findings suggest there is still considerable uncertainty between a 10 mg and a 5 mg loading dose for initiation of warfarin. In the elderly, lower initiation doses or age adjusted doses are more appropriate, leading to less higher INRs. Currently there is insufficient evidence to warrant genotype guided initiation, and adequately powered trials to detect effects on adverse events are currently warranted.

What is the psychological impact of mammographic screening on younger women with a family history of breast cancer? Findings from a prospective cohort study by the PIMMS Management Group.

PURPOSE: Studies are underway to establish the clinical effectiveness of annual mammographic screening in women younger than 50 years with a family history of breast cancer. This study investigated both the positive and negative psychological effects of screening on these women. PATIENTS AND METHODS: Women who received an immediate all-clear result after mammography (n = 1,174) and women who were recalled for additional tests before receiving an all-clear result (false positive; n = 112) completed questionnaires: 1 month before mammography, and 1 and 6 months after receiving final results. The questionnaires included measures of cancer worry, psychological consequences, and perceived benefits of breast screening. RESULTS: Women who received an immediate all-clear result experienced a decrease in cancer worry and negative psychological consequences immediately after the result, whereas women who were recalled for additional tests did not. By 6 months this cancer-specific distress had reduced significantly in both groups. Changes in levels of distress were significantly different between the two groups, but in absolute terms the differences were not large. Recalled women reported significantly greater positive psychological consequences of screening immediately after the result, and were also more positive about the benefits of screening compared with women who received an immediate all-clear result. CONCLUSION: For women receiving an immediate all-clear result, participating in annual mammographic screening is psychologically beneficial. Furthermore, women who are recalled for additional tests do not appear to be harmed by screening: these women's positive views about mammography suggest that they view any distress caused by recall as an acceptable part of screening.

Setting up and auditing guideline- and evidence-based cardiac rehabilitation.

BACKGROUND: Rehabilitation is available to only a minority of post-myocardial infarction (MI) patients and is of variable quality. Guidelines now recommend individualised care delivered by hospital, primary care and community services, but there is little evidence of the feasibility, acceptability or effectiveness of this approach. AIMS: To demonstrate the feasibility of guideline-based rehabilitation, to audit delivery and outcome and to identify problems. METHODS: A four-phase stepped programme for post-MI patients was developed based on individualised in-hospital care and aftercare from a menu of options. Delivery involved co-ordination between hospital services, primary care and community services. Self-report audit data were collected in hospital and at 3 months post-discharge by postal questionnaire and telephone calls. Clinical information was recorded from hospital, telephone and outpatient contacts. Delivery of care to patients receiving interventions was recorded. RESULTS: It was possible to negotiate individualized plans for all patients and to monitor progress for 3 months after discharge. The rehabilitation team achieved high rates of delivery of agreed interventions, considerably better than delivery by primary care. Problems largely related to difficulties and failures in communication. Patients with major social or psychological difficulties were the most difficult to treat. CONCLUSION: Guideline-based rehabilitation is feasible, but there is a need to improve the coordination of delivery of later steps of care and also to refine specialist interventions.