Evolution of biomarker guided therapy for heart failure: current concepts and trial evidence

Abstract

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple therapies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in "real-world" patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides provide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syndrome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key aspects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively establish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical.

Fig. (1)

Change in NT-proBNP by age group in the study arms. In the older patients there was an increase in NT-proBNP in the standard of care (SOC) group, while there was a decline in NT-proBNP in the guided arm of the study. Boxes indicate interquartile ranges, with a median cross line; the upper and lower whiskers extend to the 5th and 95th percentiles. Figure from Gaggin et al. [43].

Fig. (2)

The proportion of patients on triple therapy at adequate dose defined as on spironolactone and at ≥ 50% of the target dose of an angiotensin- converting enzyme inhibitor/angiotensin receptor blocker and a beta-blocker. Proportions on triple therapy were similar among randomized groups at baseline but differed significantly by study end. This proportion was higher in the BM group versus the MC group, and higher in the MC versus the UC group at end of follow-up. BM=biomarker group, MC=multidisciplinary care, UC=usual care. Figure from Berger et al. [48].

Fig. (3)

The combined end point of death or heart failure hospitalization was lower in the BM (37%) versus MC group (50%; p < 0.05) and in the MC versus UC group (65%; p = 0.04). HF=heart failure. Other abbreviations are as in Fig. (2). Figure from Berger et al. [48].

Fig. (4)

The projected total costs of cardiovascular diseases from 2015–2030 (2010 $ in billions) in the United States are shown. HBP=hypertension, CHD= coronary heart disease, CHF=congestive heart failure. Unpublished data tabulated by the American Heart Association using methods described in Heidenreich et al. Figure from Go et al. [61, 62].