Dataset Information

Protocol for a systematic review and individual participant data meta-analysis of B-type natriuretic peptide-guided therapy for heart failure.

ABSTRACT:

Background

Several aggregate data meta-analyses suggest that treatment guided by the serum concentration of natriuretic peptides (B-type natriuretic peptide (BNP) or its derivative N-terminal pro-B-type natriuretic peptide (NT-BNP)) reduces all-cause mortality compared with usual care in patients with heart failure (HF). We propose to conduct a meta-analysis using individual participant data (IPD) to estimate the effect of BNP-guided therapy on clinical outcomes, and estimate the extent of effect modification for clinically important subgroups.

Methods

We will use standard systematic review methods to identify relevant trials and assess study quality. We will include all randomized controlled trials (RCTs) of BNP-guided treatment for HF that report a clinical outcome. The primary outcome will be time to all-cause mortality. We will collate anonymized, individual patient data into a single database, and carry out appropriate data checks. We will use fixed-effects and random-effects meta-analysis methods to combine hazard ratios (HR) estimated within each RCT, across all RCTs. We will also include a meta-analysis and meta-regression analyses based on aggregate data, and combine IPD with aggregate data if we obtain IPD for a subset of trials.

Discussion

The IPD meta-analysis will allow us to estimate how patient characteristics modify treatment benefit, and to identify relevant subgroups of patients who are likely to benefit most from BNP-guided therapy. This is important because aggregate meta-analyses have suggested that clinically relevant subgroup effects exist, but these analyses have been unable to quantify the effects reliably or precisely.

Trials registration

PROSPERO 2013: CRD42013005335.

SUBMITTER: Pufulete M

PROVIDER: S-EPMC4113204 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Protocol for a systematic review and individual participant data meta-analysis of B-type natriuretic peptide-guided therapy for heart failure.

Pufulete Maria M Higgins Julian Pt JP Rogers Chris A CA Dreyer Lucy L Hollingworth William W Dayer Mark M Nightingale Angus A McDonagh Theresa T Reeves Barnaby C BC

Systematic reviews 20140502

<h4>Background</h4>Several aggregate data meta-analyses suggest that treatment guided by the serum concentration of natriuretic peptides (B-type natriuretic peptide (BNP) or its derivative N-terminal pro-B-type natriuretic peptide (NT-BNP)) reduces all-cause mortality compared with usual care in patients with heart failure (HF). We propose to conduct a meta-analysis using individual participant data (IPD) to estimate the effect of BNP-guided therapy on clinical outcomes, and estimate the extent ...[more]

PMID: 24886933

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Project description: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).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.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).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.PROSPERO CRD42013005335.

Project description:BackgroundGuidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment.MethodsIn this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure.FindingsWe recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure.InterpretationIn people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.FundingBritish Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.

Project description:IntroductionSeveral evidence-based treatments are effective for post-traumatic stress disorder (PTSD), yet a substantial proportion of patients do not respond or dropout of treatment. We describe the protocol for a systematic review and individual participant data meta-analysis (IPD-MA) aimed at assessing the effectiveness and adverse effects of psychotherapy and pharmacotherapy interventions for treating PTSD. Additionally, we seek to examine moderators and predictors of treatment outcomes.Method and analysisThis IPD-MA includes randomised controlled trials comparing psychotherapy and pharmacotherapy interventions for PTSD. PubMed, Embase, PsycINFO, PTSDpubs and CENTRAL will be screened up till the 11th of January 2021. The target population is adults with above-threshold baseline PTSD symptoms on any standardised self-report measure. Trials will only be eligible if at least 70% of the study sample have been diagnosed with PTSD by means of a structured clinical interview. The primary outcomes of this IPD-MA are PTSD symptom severity, and response rate. Secondary outcomes include treatment dropout and adverse effects. Two independent reviewers will screen major bibliographic databases and past reviews. Authors will be contacted to contribute their participant-level datasets. Datasets will be merged into a master dataset. A one-stage IPD-MA will be conducted focusing on the effects of psychological and pharmacological interventions on PTSD symptom severity, response rate, treatment dropout and adverse effects. Subsequent analyses will focus on examining the effect of moderators and predictors of treatment outcomes. These will include sociodemographic, treatment-related, symptom-related, resilience, intervention, trauma and combat-related characteristics. By determining the individual factors that influence the effectiveness of specific PTSD treatments, we will gain insight into personalised treatment options for PTSD.Ethics and disseminationSpecific ethics approval for an IPD-MA is not required as this study entails secondary analysis of existing anonymised data. The results of this study will be published in peer-reviewed scientific journals and presentations.

Dataset Information

Protocol for a systematic review and individual participant data meta-analysis of B-type natriuretic peptide-guided therapy for heart failure.

Background

Methods

Discussion

Trials registration

Publications

Protocol for a systematic review and individual participant data meta-analysis of B-type natriuretic peptide-guided therapy for heart failure.

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