Biomarker-guided therapy in chronic heart failure: A meta-analysis of randomized controlled trials

Background Measurement of circulating natriuretic peptides has been shown to play an important role in diagnosis and prognosis in patients with chronic heart failure. Whether serial natriuretic peptide measurements to aid in the titration of therapy can improve heart failure outcomes remains uncertain. We performed a quantitative meta-analysis of available randomized controlled trials to determine whether titration of therapy based on natriuretic peptide measurements improves mortality in chronic heart failure. Methods We identified potentially relevant studies through a search of MEDLINE (1996-2009), ISI Web of Knowledge (1996-2009), Cochrane Central Register of Controlled Trials (1996-2009), clinicaltrials.gov, proceedings of major US and European cardiology meetings (2000-2009), and bibliographic review of secondary sources. Search terms were "biomarker," "natriuretic peptide," "B-type natriuretic peptide," "N-terminal B-type natriuretic peptide," and "heart failure." Studies were included if they were prospective, randomized controlled trials of patients with chronic heart failure, they randomized patients to a strategy of titrating medical therapy based on the level of a circulating biomarker compared to a parallel control group, and they reported all-cause mortality. Results Six studies randomizing 1627 patients met criteria for inclusion. Pooled analysis showed a significant mortality advantage for biomarker-guided therapy (hazard ratio was 0.69, 95% CI 0.55-0.86) compared to control. There was no quantitative evidence of heterogeneity between studies (P = .42). Conclusions Titration of therapy incorporating serial BNP or N-terminal pro-B-type natriuretic peptide levels is associated with a significant reduction in all-cause mortality compared to usual care in patients with chronic heart failure. (Am Heart J 2009;158:422-30.)