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

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