Page 82 - Biomarkers for risk stratification and guidance in heart failure

Which heart failure patients profit from natriuretic peptide-guided therapy?
INTRODUCTION
A recent individual patient data meta-analysis showed that (N-terminal pro-) brain natriuretic peptide (NT-proBNP)-guided therapy improves outcome in heart failure (HF), at least in those aged 75 years or younger;1 in line with other aggregate data meta-analyses of (NT-pro)BNP-guided therapy in HF.2,3 Thus, treatment effects of (NT-pro)BNP-guided therapy may be dependent on age.1 One possible explanation of the apparent dependency of the efficacy of natriuretic peptide (NP)-guided treatment upon age is that comorbidities, which are more common with increasing age, may limit HF therapy titration and/or reduce the benefits of treatment. This question has, however, not yet been appropriately addressed.
In HF, data on the elderly, those patients with significant comorbidities and
those with HFpEF are scant. Therefore, these questions may not only shed further 4 light on the efficacy of biomarker-guided therapy in HF, but also on potential
differences in treatment response dependent upon age and comorbidities. As
most patients included in the large randomized therapeutic trials that underpin
clinical practice guidelines4 had HF with reduced left-ventricular ejection fraction
(HFrEF), were not truly elderly and had few comorbidities, the findings from these
trials might be less applicable to the majority of patients seen in daily practice;
thus, perceived shortcomings of biomarker-guided HF care may reflect limitations
of therapeutic efficacy in patients with co-morbidity.
Moreover, no treatment interaction with left ventricular ejection fraction (LVEF) was seen in previous analysis, but less than 10% of the trial participants had preserved LVEF (HFpEF) >45%, precluding any firm conclusions in this patient group. As no randomized therapeutic trials in HFpEF have shown convincing benefit from medical therapy,5 - 7 it is uncertain whether (NT-pro)BNP-guidance is equally effective in HFpEF and HFrEF, i.e. LVEF ≤45%.
Therefore, we investigated (i) potential interactions between comorbidities and (ii) age with treatment response, as well as (iii) potential differences in treatment response between HFrEF and HFpEF in patients included in randomized trials of (NT-pro)BNP-guided therapy in HF.
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